Study of TSR-042, an Anti-programmed Cell Death-1 Receptor (PD-1) Monoclonal Antibody, in Participants With Advanced Solid Tumors

Neoplasms Clinical Trial

— GARNET  

Official title:

A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-042, an Anti-PD-1 Monoclonal Antibody, in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02715284
• Other study ID #: 213346
• Secondary ID: 4010-01-001
• Status: Recruiting
• Phase: Phase 1
• Start date: March 7, 2016
• Est. completion date: October 27, 2027

Study information

• Verified date: August 2023
• Source: Tesaro, Inc.
• Contact: US GSK Clinical Trials Call Center
• Phone: 877-379-3718
• Email: GSKClinicalSupportHD[@]gsk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a multi-center, open-label, first-in-human Phase 1 study evaluating the anti-programmed death receptor 1 (anti-PD-1) antibody dostarlimab (also known as TSR-042) n participants with advanced solid tumors who have limited available treatment options. The study will be conducted in 2 parts with Part 1 consisting of safety evaluation, pharmacokinetics (PK), and pharmacodynamics (PDy) of escalating doses of dostarlimab. Dose escalation will be based on ascending weight-based dose levels (DLs) of dostarlimab and will continue until the maximum tolerated dose (MTD) is reached or may be stopped at any dose level up to the highest dose of 20 milligrams per kilograms (mg/kg) based on emerging safety and PK/PDy data. Part 2 will be conducted in two subparts, Part 2A (fixed-dose safety evaluation cohorts) and Part 2B (expansion cohorts). Part 2A of the study will evaluate the safety and tolerability of dostarlimab at fixed doses of 500 mg administered every 3 weeks (Q3W) and 1000 mg administered every 6 weeks (Q6W). Part 2B of the study will examine the safety and clinical activity of dostarlimab in cohorts of participants with specific types of advanced solid tumors.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 740
• Est. completion date: October 27, 2027
• Est. primary completion date: May 15, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participant is at least 18 years of age.

• Participant has proven recurrent or advanced solid tumor and has disease progression after treatment with available anti cancer therapies, or is intolerant to treatment that meets the following requirements for the part of the study they will participate in:

• a. Part 1: Any histologically or cytologically proven recurrent advanced solid tumor

• b. Part 2A: : Any histologically or cytologically proven recurrent advanced solid tumor

• c. Part 2B: Histologically of cytologically proven recurrent or advanced solid tumor with measurable lesion(s) per RECIST version 1.1 and meets one of the following disease types:

• The criteria below should be met for participant participating in: Cohort A1 (dMMR/MSI-H endometrial cancer) and Cohort A2 (MMR-proficient/MSS endometrial cancer)

• Participants who have progressed on or after platinum doublet therapy

• Participants have received no more than 2 lines of anti-cancer therapy for recurrent or advanced (>=Stage IIIB) disease. Prior treatment with hormone therapies is acceptable and does not count towards the number of anti-cancer therapies noted in the criterion above for this cohort.

• All endometrial cancer histologies are allowed except endometrial sarcoma (including carcinosarcoma).

• Participants must submit 2 scans demonstrating increase in tumor measurement that meet criteria for PD on or after the latest systemic anti-cancer therapy based on RECIST Version 1.1 to Central Radiology prior to the first dose of dostarlimab.

• Presence of at least 1 measurable lesion on Baseline scan will be confirmed by central radiology review.

• Status of tumor MMR/MSI: Participants can be screened based on local MMR/MSI testing results using immunohistochemistry (IHC), polymerase chain reaction (PCR), or next generation sequencing (NGS) performed in a certified local laboratory, but participant eligibility needs to be determined by MMR IHC results. For participant with available local MMR IHC results for the respective cohort(s), tumor samples have to be submitted to a central IHC laboratory and its quality has to be checked and cleared prior to Cycle 1 Day 1 (C1D1). For participants without available local MMR IHC test results (participants with local PCR or NGS test results), central IHC results have to confirm eligibility prior to proceeding with other screening procedures. After the central IHC test is completed, remaining tumor tissue may be tested for further exploratory biomarkers or may be sent to a central NGS laboratory for further testing.

• Cohort E - Participants with NSCLC who progressed after at least 1 prior platinum-based systemic chemotherapy regimen for recurrent or advanced disease. Chemotherapy regimen in the adjuvant or neoadjuvant setting following surgery and/or radiation is acceptable if recurrent or advanced disease develops within 6 months from completion of therapy.

• Participants with a known epidermal growth factor receptor (EGFR) mutation must have received a chemotherapy regimen and an EGFR tyrosine-kinase inhibitor (TKI) (e.g., erlotinib, gefitinib, afatinib, or experimental)

• Participants with a known anaplastic lymphoma kinase (ALK) translocation must have received a chemotherapy regimen and an ALK inhibitor (e.g., crizotinib, ceritinib or experimental)

• Cohort F - Participants with recurrent or advanced dMMR/MSI-H solid tumors except endometrial cancers and gastrointestinal cancers, who have received prior systemic therapy and who have no alternative treatment options. Prior treatment with hormone therapies alone given for recurrent or advanced disease is acceptable and does not count towards the number of anti-cancer therapies.

• Measurable lesion by RECIST 1.1 Radiology on baseline scan will be confirmed by central radiology review prior to first dose of dostarlimab. Patients with primary CNS tumor should provide brain MRI at baseline.

• a. Presence of deficient mismatch repair (dMMR) and/or microsatellite instability (MSI-H) in the tumor defined by either:

• b. deficient DNA mismatch repair (dMMR); MMR status must be assessed by immunohistochemistry (IHC) for MMR protein expression (MLH1, MSH2, MSH6, PMS2) where loss of one or more proteins indicates dMMR; dMMR may be determined either locally or by the central reference lab; OR

• c. Microsatelillite instability (MSI-H); MSI-H as determined by polymerase chain reaction (PCR) or by tissue Next generation sequencing (NGS); MSI-H may be determined locally

• Cohort G: Participants must have recurrent high-grade serous, endometrioid, or clear cell ovarian, fallopian tube, or primary peritoneal cancer. Participants must have presence of at least 1 measurable lesion on Baseline scan that will be confirmed by central radiology review.

• Participants must be considered resistant to the last administered platinum therapy, that is, the time from the last administered platinum dose until the initial documented progression (as evidenced by radiographic progression per RECIST version 1.1) must be less than 6 months.

• Participants must have completed at least 1 but no more than 3 prior lines of therapy for advanced or metastatic ovarian cancer. Neoadjuvant, adjuvant, and the combination of both will be considered as 1 line of therapy. Treatment with single-agent bevacizumab given as maintenance is not counted as a separate line of therapy. If a therapeutic regimen is modified or changed for a reason other than lack of response or PD (such as allergic reaction, toxicity, or drug availability), this is not counted as a separate line of therapy. The use of single-agent hormonal therapy given for reasons other than PD per RECIST version v1.1 (i.e., hormonal therapy given for increasing Cancer antigen [CA]-125 levels) is not counted as a separate line of therapy.

• Participants must have been previously treated with platinum-based regimen, taxane agent(s), and bevacizumab (bevacizumab could be used as a single agent or in combination with another agent, in frontline therapy, as maintenance, or for treatment of recurrent disease).

• Part 2B: Participants must have archival tumor tissue available that is formalin-fixed and paraffin-embedded (FFPE).

• For participants who do not have archival tissue, a new biopsy must be performed to obtain a tissue sample prior to study treatment initiation. For participants without available archival tissue, the biopsy should be taken from the tumor lesions (either primary or metastatic) that have easy accessibility and low biopsy-associated risks and will exclude biopsies of the liver, brain, lung/mediastinum, pancreas, or endoscopic procedures extending beyond the esophagus, stomach or bowel.

• For Cohort F an FFPE tissue sample must be submitted to the central laboratory for testing. For patients with available local MMR/MSI-H results, tumor samples have to be submitted to a central laboratory and its quality has to be checked and cleared prior to C1D1

• For Cohort G, participant must provide formalin fixed paraffin embedded (FFPE) tumor tissue block(s) with sufficient tumor content (as confirmed by the Sponsor's designated central laboratory) during screening to enable, for example, measures of homologous recombination pathway defects and PD-L1 status. The use of slides created from paraffin-embedded tissue as opposed to FFPE blocks must be approved by the Sponsor.

• Female participants must have a negative serum pregnancy test within 72 hours prior to the date of the first dose of study medication: unless they are of non-child bearing potential.

• Non child bearing potential is defined as: >= 45 years of age and has not had menses for > 1 year; Amenorrheic for < 2 years without a hysterectomy and oophorectomy and have a follicle- stimulating hormone (FSH) value in the postmenopausal range upon pre-study (screening) evaluation. Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound, magnetic resonance imaging (MRI) or computed tomography (CT) scan. Tubal ligation must be confirmed with medical records of the actual procedure.

• Female participants of childbearing potential must agree to use 1 highly effective form of contraception with their partner starting with the screening visit through 150 days after the last dose of study therapy.

• Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of <= 2 for Part 1 and <= 1 for Part 2.

• Participant has an adequate organ function.

Exclusion Criteria

• Participant has received prior therapy with an anti- programmed death receptor 1 (anti-PD-1), anti-PD-1- ligand-1 (anti-PD-L1), or anti-PD-1 ligand-2 (anti-PD- L2) agent.

• Participant has a known uncontrolled central nervous system (CNS) metastases and/or carcinomatous meningitis.

• Participant has a known additional malignancy that progressed or required active treatment within the last 2 years. Exceptions include basal cell carcinoma of the skin, squamous cell cancer (SqCC) of the skin that has undergone potentially curative therapy, or in situ cervical cancer, or other neoplastic condition which has undergone curative therapy and is considered cured by the investigator.

• Participant is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease or active infection requiring systemic therapy. Specific examples include, but are not limited to, active, non-infectious pneumonitis; uncontrolled ventricular arrhythmia; recent (within 90 days) myocardial infarction; uncontrolled major seizure disorder; unstable spinal cord compression; superior vena cava syndrome; or any psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study (including obtaining informed consent).

• Participant is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study, starting with the Screening Visit through 150 days after the last dose of study treatment.

• Participant has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.

• Participant has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).

• Participant has a known active hepatitis B (eg, hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (eg, hepatitis C virus ribonucleic acid (HCV RNA) (qualitative) is detected).

• Participant has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease- modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Use of inhaled steroids, local injection of steroids, and steroid eye drops are allowed.

• Participant has as history of interstitial lung disease.

• Participant has not recovered (i.e., to <= Grade 1 or to Baseline) from radiation- and chemotherapy-induced AEs or received transfusion of blood products (including platelets or red blood cells) or administration of colony-stimulating factors (including granulocyte-colony stimulating factor [G-CSF], granulocyte macrophage colony-stimulating factor [GM-CSF] or recombinant erythropoietin) within 3 weeks prior to the first dose of study drug.

• Participant has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to the first dose of study drug.

• Participant has received prior anti-cancer therapy (chemotherapy, targeted therapies, radiotherapy, or immunotherapy) within 21 days, or less than 5 times the half-life of the most recent therapy prior to study Day 1, whichever is shorter.

• Participant has not recovered adequately (<= Grade 1) from AEs and/or complications from any major surgery prior to starting therapy.

• Participant has received a live vaccine within 14 days of planned start of study therapy.

• Participant has a known hypersensitivity to dostarlimab components or excipients.

• For Cohort G, participants will not be eligible if they meet the following criteria:

Participants who experienced disease progression within 3 months (as evidenced by radiographic progression per RECIST) of first-line platinum therapy.

• Participants with known deleterious or suspicious deleterious mutation in BRCA1 or BRCA2 genes (local testing permitted).

• Participants has received prior therapy with a poly(adenosine diphosphate-ribose) polymerase (PARP)-1/PARP-2 inhibitor.

• Participant has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, might interfere with the participant's participation for the full duration of the study treatment, or is not in the best interest of the participant to participate.

• Participant is immunocompromised. Participants with splenectomy are allowed.

Related Conditions & MeSH terms

• Neoplasms

Intervention

Biological:
• Dostarlimab
Dostarlimab (160 mg, 20 mg/mL; or 500 mg, 50 mg/mL) is a humanized monoclonal antibody that binds with high affinity to PD-1 resulting in inhibition of binding to programmed death receptor ligands 1 and 2 (PD-L1 and PD-L2). Dostarlimab will be administered via a 30 minute IV infusion on Day 1 and Day 15 of each cycle in Part 1. For additional patients enrolled specifically to better characterize the PK/PDy profile in Part 1, dostarlimab administration during Cycle 1 will only occur on Day 1 with the second dose administered on Cycle 2/Day 1 and Q2W thereafter. For Part 2A and 2B, dostarlimab will be administered on Day 1 of each treatment cycle. Cycle duration for Q3W dosing is 21 days and Q6W dosing is 42 days.

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Ciudad de Córdoba	Córdova
Argentina	GSK Investigational Site	Córdoba	Córdova
Argentina	GSK Investigational Site	Florida	Buenos Aires
Brazil	GSK Investigational Site	Barretos	São Paulo
Brazil	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul
Brazil	GSK Investigational Site	Ribeirao Preto	São Paulo
Brazil	GSK Investigational Site	Rio de Janeiro
Brazil	GSK Investigational Site	Sao Jose Do Rio Preto	São Paulo
Brazil	GSK Investigational Site	Sao Paulo
Brazil	GSK Investigational Site	São Paulo
Canada	GSK Investigational Site	Calgary	Alberta
Canada	GSK Investigational Site	Edmonton	Alberta
Canada	GSK Investigational Site	Hamilton	Ontario
Canada	GSK Investigational Site	Kelowna	British Columbia
Canada	GSK Investigational Site	London	Ontario
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Vancouver	British Columbia
Czechia	GSK Investigational Site	Horovice
Czechia	GSK Investigational Site	Zlin
Denmark	GSK Investigational Site	Copenhagen
Denmark	GSK Investigational Site	Odense
France	GSK Investigational Site	Bordeaux Cedex
France	GSK Investigational Site	Caen Cedex 05
France	GSK Investigational Site	Dijon
France	GSK Investigational Site	Lille
France	GSK Investigational Site	Marseille Cedex 9
France	GSK Investigational Site	Paris cedex 12
France	GSK Investigational Site	Paris Cedex 15
France	GSK Investigational Site	Saint-Herblain
France	GSK Investigational Site	Villejuif Cedex
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	MIlano
Italy	GSK Investigational Site	Modena	Emilia-Romagna
Italy	GSK Investigational Site	Napoli	Campania
Italy	GSK Investigational Site	Roma	Lazio
Italy	GSK Investigational Site	Verona	Veneto
Korea, Republic of	GSK Investigational Site	Gwangju
Korea, Republic of	GSK Investigational Site	Incheon
Korea, Republic of	GSK Investigational Site	Seongnam
Korea, Republic of	GSK Investigational Site	Seongnam si
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Suwon
Mexico	GSK Investigational Site	Cordoba	Veracruz
Mexico	GSK Investigational Site	Mexico	Ciudad De Mexico
Mexico	GSK Investigational Site	Monterrey	Nuevo León
Mexico	GSK Investigational Site	Veracruz
Poland	GSK Investigational Site	Gdynia
Poland	GSK Investigational Site	Lublin
Poland	GSK Investigational Site	Lublin
Poland	GSK Investigational Site	Olsztyn
Poland	GSK Investigational Site	Olsztyn
Poland	GSK Investigational Site	Torun
Poland	GSK Investigational Site	Warszawa
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Córdoba
Spain	GSK Investigational Site	Girona
Spain	GSK Investigational Site	Hospitalet de Llobregat (Barcelona)
Spain	GSK Investigational Site	Jaén
Spain	GSK Investigational Site	Lerida
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Málaga
Spain	GSK Investigational Site	Murcia (El Palmar)
Spain	GSK Investigational Site	Pamplona
Spain	GSK Investigational Site	Santander
Spain	GSK Investigational Site	Santiago de Compostela
Spain	GSK Investigational Site	Sevilla
Spain	GSK Investigational Site	Valencia
Spain	GSK Investigational Site	Valencia
Spain	GSK Investigational Site	Zaragoza
United Kingdom	GSK Investigational Site	Aberdeen
United Kingdom	GSK Investigational Site	Headington, Oxford
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	Manchester
United Kingdom	GSK Investigational Site	Newcastle upon Tyne
United States	GSK Investigational Site	Albany	New York
United States	GSK Investigational Site	Atlanta	Georgia
United States	GSK Investigational Site	Augusta	Georgia
United States	GSK Investigational Site	Baltimore	Maryland
United States	GSK Investigational Site	Birmingham	Alabama
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Brooklyn	New York
United States	GSK Investigational Site	Charlotte	North Carolina
United States	GSK Investigational Site	Charlottesville	Virginia
United States	GSK Investigational Site	Chicago	Illinois
United States	GSK Investigational Site	Chicago	Illinois
United States	GSK Investigational Site	Cleveland	Ohio
United States	GSK Investigational Site	Columbus	Ohio
United States	GSK Investigational Site	Columbus	Ohio
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Detroit	Michigan
United States	GSK Investigational Site	Encinitas	California
United States	GSK Investigational Site	Farmington	New Mexico
United States	GSK Investigational Site	Fayetteville	Arkansas
United States	GSK Investigational Site	Goodyear	Arizona
United States	GSK Investigational Site	Hilliard	Ohio
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Jacksonville	Florida
United States	GSK Investigational Site	Jamaica	New York
United States	GSK Investigational Site	Kansas City	Missouri
United States	GSK Investigational Site	La Jolla	California
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Milwaukee	Wisconsin
United States	GSK Investigational Site	Morgantown	West Virginia
United States	GSK Investigational Site	Nashville	Tennessee
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	Newport Beach	California
United States	GSK Investigational Site	Oklahoma City	Oklahoma
United States	GSK Investigational Site	Orange	California
United States	GSK Investigational Site	Philadelphia	Pennsylvania
United States	GSK Investigational Site	Philadelphia	Pennsylvania
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	Portland	Oregon
United States	GSK Investigational Site	Providence	Rhode Island
United States	GSK Investigational Site	Rochester	Minnesota
United States	GSK Investigational Site	Salt Lake City	Utah
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Francisco	California
United States	GSK Investigational Site	San Marcos	California
United States	GSK Investigational Site	Santa Monica	California
United States	GSK Investigational Site	Scarborough	Maine
United States	GSK Investigational Site	Scottsdale	Arizona
United States	GSK Investigational Site	Seattle	Washington
United States	GSK Investigational Site	Seattle	Washington
United States	GSK Investigational Site	Spokane	Washington
United States	GSK Investigational Site	Spokane	Washington
United States	GSK Investigational Site	Spokane	Washington
United States	GSK Investigational Site	Tampa	Florida
United States	GSK Investigational Site	Washington	District of Columbia
United States	GSK Investigational Site	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Tesaro, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Canada,  Czechia,  Denmark,  France,  Italy,  Korea, Republic of,  Mexico,  Poland,  Spain,  United Kingdom, 

References & Publications (7)

Kristeleit R, Mathews C, Redondo A, Boklage S, Hanlon J, Im E, Brown J. Patient-reported outcomes in the GARNET trial in patients with advanced or recurrent mismatch repair-deficient/microsatellite instability-high endometrial cancer treated with dostarlimab. Int J Gynecol Cancer. 2022 Aug 16;32(10):1250-7. doi: 10.1136/ijgc-2022-003492. Online ahead of print. — View Citation

Kuchimanchi M, Dabrowski C, Lu S, Melhem M. Dostarlimab, an anti-programmed death-1 monoclonal antibody, does not cause QT prolongation in patients with solid tumours: A concentration-QT analysis. Br J Clin Pharmacol. 2023 Jul;89(7):2272-2282. doi: 10.1111/bcp.15700. Epub 2023 Mar 20. — View Citation

Kumar S, Ghosh S, Sharma G, Wang Z, Kehry MR, Marino MH, Neben TY, Lu S, Luo S, Roberts S, Ramaswamy S, Danaee H, Jenkins D. Preclinical characterization of dostarlimab, a therapeutic anti-PD-1 antibody with potent activity to enhance immune function in in vitro cellular assays and in vivo animal models. MAbs. 2021 Jan-Dec;13(1):1954136. doi: 10.1080/19420862.2021.1954136. — View Citation

Oaknin A, Gilbert L, Tinker AV, Brown J, Mathews C, Press J, Sabatier R, O'Malley DM, Samouelian V, Boni V, Duska L, Ghamande S, Ghatage P, Kristeleit R, Leath C III, Guo W, Im E, Zildjian S, Han X, Duan T, Veneris J, Pothuri B. Safety and antitumor activity of dostarlimab in patients with advanced or recurrent DNA mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) or proficient/stable (MMRp/MSS) endometrial cancer: interim results from GARNET-a phase I, single-arm study. J Immunother Cancer. 2022 Jan;10(1):e003777. doi: 10.1136/jitc-2021-003777. — View Citation

Patnaik A, Weiss GJ, Rasco DW, Blaydorn L, Mirabella A, Beeram M, Guo W, Lu S, Danaee H, McEachern K, Im E, Sachdev JC. Safety, antitumor activity, and pharmacokinetics of dostarlimab, an anti-PD-1, in patients with advanced solid tumors: a dose-escalation phase 1 trial. Cancer Chemother Pharmacol. 2022 Jan;89(1):93-103. doi: 10.1007/s00280-021-04358-3. Epub 2021 Nov 8. — View Citation

Patterson M, Beausang LA, Rup B, Bowsher R, Krug K, Gunn G, Melham M, Lu S.A Bridging Assay for Detection and Characterization of Anti-Drug Antibodies to Dostarlimab, a New Anti-PD-1 Therapeutic Monoclonal Antibody .2021;7(11) DOI: DOI 10.1186/s41120-021-00045-y

Zhang XT, Chen H, Shao W, Zhongping JL, Melham M, Lu S.A Competitive Ligand Binding Assay to Measure Antidrug Antibodies Against Dostarlimab (TSR-042).2021; DOI: 10.1186/s41120-021-00039-w

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Number of participants with treatment emergent AEs (TEAEs)	An adverse event (AE) is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including clinically significant abnormal laboratory findings), symptom, or disease temporally associated with the use of an investigational product, whether or not considered related to the product. TEAEs defined as any AE either reported for the first time or worsening of a pre-existing event after first dose of study treatment.	Up to 2 years
Primary	Part 1: Number of participants with immune related AEs of interest	Participants with immune related AEs of interest will be assessed.	Up to 2 years
Primary	Part 1: Number of participants with abnormal hematology parameters	Blood samples will be collected to assess the following hematology parameters: hemoglobin, Mean corpuscular (MCV), white blood cell count (WBC count), platelets, mean platelet volume, differential WBC count and coagulation factors including International normalized ratio (INR), activated partial thromboplastin time (aPTT) and prothrombin time (PT).	Up to 2 years
Primary	Part 1: Number of participants with abnormal clinical chemistry parameters	Blood samples will be collected to assess the following chemistry parameters: sodium, potassium, calcium, magnesium, chloride, glucose, creatinine, urea or blood urea nitrogen (BUN), amylase, bilirubin, alkaline phosphatase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total protein, albumin, lactate dehydrogenase.	Up to 2 years
Primary	Part 1: Number of participants with abnormal thyroid function	Blood samples will be collected to assess the levels of thyroid-stimulating hormone (TSH); triiodothyronine (T3), or free triiodothyronine (FT3) and free thyroxine (FT4).	Up to 2 years
Primary	Part 1: Number of participants with abnormal urine parameters	Urine samples will be collected to evaluate specific gravity, leucocyte esterase, nitrite, blood, protein, glucose, and ketones.	Up to 2 years
Primary	Part 1: Number of participants with abnormal vital signs	Blood pressure, pulse rate, respiratory rate and temperature will be assessed.	Up to 2 years
Primary	Part 1: Number of participants with abnormal electrocardiogram (ECG) parameters	Participants will be supine or in a semi-recumbent position and rested for approximately 2 minutes before ECGs are recorded.	Up to 2 years
Primary	Part 1: Number of participants with abnormal physical examination.	Physical examinations including weight will be assessed.	Up to 2 years
Primary	Part 1: Number of participants receiving concomitant medications	Concomitant medications will be recorded.	Up to 2 years
Primary	Part 2A: Number of participants with TEAEs	An AE is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including clinically significant abnormal laboratory findings), symptom, or disease temporally associated with the use of an investigational product, whether or not considered related to the product. TEAEs defined as any AE either reported for the first dose of study treatment.	Up to 2 years
Primary	Part 2A: Number of participants with immune related AEs of interest	Participants with immune related AEs of interest will be assessed.	Up to 2 years
Primary	Part 2A: Number of participants with abnormal hematology parameters	Blood samples will be collected to assess the following hematology parameters: hemoglobin, MCV, white WBC count, platelets, mean platelet volume, differential WBC count and coagulation factors including INR, aPTT and PT.	Up to 2 years
Primary	Part 2A: Number of participants with abnormal clinical chemistry parameters	Blood samples will be collected to assess the following chemistry parameters: sodium, potassium, calcium, magnesium, chloride, glucose, creatinine, urea or BUN, amylase, bilirubin, AST, ALT, total protein, albumin, lactate dehydrogenase.	Up to 2 years
Primary	Part 2A: Number of participants with abnormal thyroid function	Blood samples will be collected to assess the levels of TSH, T3, or FT3 and FT4.	Up to 2 years
Primary	Part 2A: Number of participants with abnormal urine parameters	Urine samples will be collected to evaluate specific gravity, leucocyte esterase, nitrite, blood, protein, glucose, and ketones.	Up to 2 years
Primary	Part 2A: Number of participants with abnormal vital signs	Blood pressure, pulse rate, respiratory rate and temperature will be assessed.	Up to 2 years
Primary	Part 2A: Number of participants with abnormal ECG	Participants will be supine or in a semi-recumbent position and rested for approximately 2 minutes before ECGs are recorded.	Up to 2 years
Primary	Part 2A: Number of participants with abnormal physical examination	Physical examination including weight will be assessed.	Up to 2 years
Primary	Part 2A: Number of participants receiving concomitant medications	Concomitant medications will be recorded.	Up to 2 years
Primary	Part 2B: Number of participants with TEAEs	An AE is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including clinically significant abnormal laboratory findings), symptom, or disease temporally associated with the use of an investigational product, whether or not considered related to the product. TEAEs defined as any AE either reported for the first dose of study treatment.	Up to 2 years
Primary	Part 2B: Number of participants with immune related AEs of interest	Participants with immune related AEs of interest will be assessed.	Up to 2 years
Primary	Part 2B: Number of participants with abnormal hematology parameters	Blood samples will be collected to assess the following hematology parameters: hemoglobin, MCV, white WBC count, platelets, mean platelet volume, differential WBC count and coagulation factors including INR, aPTT and PT.	Up to 2 years
Primary	Part 2B: Number of participants with abnormal clinical chemistry parameters	Blood samples will be collected to assess the following chemistry parameters: sodium, potassium, calcium, magnesium, chloride, glucose, creatinine, urea or BUN, amylase, bilirubin, AST, ALT, total protein, albumin, lactate dehydrogenase.	Up to 2 years
Primary	Part 2B: Number of participants with abnormal thyroid function	Blood samples will be collected to assess the levels of TSH, T3, or FT3 and FT4.	Up to 2 years
Primary	Part 2B: Number of participants with abnormal urine parameters	Urine samples will be collected to evaluate specific gravity, leucocyte esterase, nitrite, blood, protein, glucose, and ketones.	Up to 2 years
Primary	Part 2B: Number of participants with abnormal vital signs	Blood pressure, pulse rate, respiratory rate and temperature will be assessed.	Up to 2 years
Primary	Part 2B: Number of participants with abnormal ECG parameters	Participants will be supine or in a semi-recumbent position and rested for approximately 2 minutes before ECGs are recorded.	Up to 2 years
Primary	Part 2B: Number of participants with abnormal physical examination	Physical examinations including weight will be assessed.	Up to 2 years
Primary	Part 2B: Number of participants receiving concomitant medications	Concomitant medications will be recorded.	Up to 2 years
Primary	Part 2B: Cohort A1 Overall Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	ORR is defined as the proportion of participants achieving complete response (CR) or partial response (PR) as assessed by investigator per RECIST version 1.1 will be evaluated.	Up to 2 years
Primary	Part 2B: Cohort F ORR by RECIST version 1.1	ORR is defined as the proportion of participants achieving CR or PR as assessed by investigator per RECIST version 1.1 will be evaluated.	Up to 2 years
Primary	Part 2B: Cohort A2 ORR by RECIST version 1.1	ORR is defined as the proportion of participants achieving CR or PR as assessed by investigator per RECIST version 1.1 will be evaluated.	Up to 2 years
Primary	Part 2B: Cohort G ORR by RECIST version 1.1	ORR is defined as the proportion of participants achieving CR or PR as assessed by investigator per RECIST version 1.1 will be evaluated.	Up to 2 years
Primary	Part 2B: Cohort E ORR by immune related Response Evaluation Criteria in Solid Tumors per irRECIST	ORR is defined as the proportion of participants achieving CR or PR as assessed by investigator per irRECIST will be evaluated.	Up to 2 years
Primary	Part 2B: Cohort A1 Duration of response (DOR)	DOR is defined as the time from first documentation of CR or PR by RECIST version 1.1 until the time of first documentation of progressive disease (PD) evaluated using RECIST version 1.1 based on independent blinded central review, or death due to any cause.	Up to 2 years
Primary	Part 2B: Cohort F Duration of response (DOR)	DOR is defined as the time from first documentation of CR or PR by RECIST version 1.1 until the time of first documentation of PD evaluated using RECIST version 1.1 based on independent blinded central review, or death due to any cause.	Up to 2 years
Primary	Part 2B: Cohort A2 Duration of response (DOR)	DOR is defined as the time from first documentation of CR or PR by RECIST version 1.1 until the time of first documentation of PD evaluated using RECIST version 1.1 based on independent blinded central review, or death due to any cause.	Up to 2 years
Secondary	Part 2B: Cohort A1 ORR by independent blinded central review using RECIST version 1.1	ORR is defined as the proportion of participants achieving CR or PR as assessed by investigator per RECIST version 1.1 will be evaluated.	Up to 2 years
Secondary	Part 2B: Cohort F ORR by independent blinded central review using RECIST version 1.1	ORR is defined as the proportion of participants achieving CR or PR as assessed by investigator per RECIST version 1.1 will be evaluated.	Up to 2 years
Secondary	Part 2B: Cohort A1 Immune-related objective response rate (irORR) by irRECIST	Immune related objective response rate will be evaluated.	Up to 2 years
Secondary	Part 2B: Cohort A2 irORR by irRECIST	Immune related objective response rate will be evaluated.	Up to 2 years
Secondary	Part 2B: Cohort F irORR by irRECIST	Immune related objective response rate will be evaluated.	Up to 2 years
Secondary	Part 2B: Cohort G irORR by irRECIST	Immune related objective response rate will be evaluated.	Up to 2 years
Secondary	Part 2B: Cohort A1 Duration of response (DOR) based on independent blinded central review using RECIST version 1.1	DOR is defined as the time from first documentation of CR or PR by RECIST version 1.1 until the time of first documentation of progressive disease (PD) evaluated using RECIST version 1.1 based on independent blinded central review, or death due to any cause.	Up to 2 years
Secondary	Part 2B: Cohort F DOR based on independent blinded central review using RECIST version 1.1	DOR is defined as the time from first documentation of CR or PR by RECIST version 1.1 until the time of first documentation of PD evaluated using RECIST version 1.1 based on independent blinded central review, or death due to any cause.	Up to 2 years
Secondary	Part 2B: Cohort G DOR based on independent blinded central review using RECIST version 1.1	DOR is defined as the time from first documentation of CR or PR by RECIST version 1.1 until the time of first documentation of PD evaluated using RECIST version 1.1 based on independent blinded central review, or death due to any cause.	Up to 2 years
Secondary	Part 2B: Cohort A1 Disease control rate	Disease control rate is the proportion of participants achieving CR, PR, or SD per RECIST v1.1 based on independent blinded central review.	Up to 2 years
Secondary	Part 2B: Cohort A2 Disease control rate	Disease control rate is the proportion of participants achieving CR, PR, or SD per RECIST v1.1 based on independent blinded central review.	Up to 2 years
Secondary	Part 2B: Cohort F Disease control rate	Disease control rate is the proportion of participants achieving CR, PR, or SD per RECIST v1.1 based on independent blinded central review.	Up to 2 years
Secondary	Part 2B: Cohort G Disease control rate	Disease control rate is the proportion of participants achieving CR, PR, or SD per RECIST v1.1 based on independent blinded central review.	Up to 2 years
Secondary	Part 2B: Immune related disease control rate	The proportion of participants achieving CR, PR, or SD per irRECIST based on Investigators' assessment.	Up to 2 years
Secondary	Part 2B: Immune related duration of response	The time from first documentation of CR or PR by irRECIST until the time of first documentation of PD (subsequently confirmed) per irRECIST based on Investigators' assessment.	Up to 2 years
Secondary	Part 2B: Progression free survival	The time from date of first dose to the earlier date of assessment of progression or death by any cause in the absence of progression based on: (1) the time of first documentation of PD per RECIST v1.1 (for Cohorts A1, A2, F, and G only); and (2) the time of first documentation of PD (subsequently confirmed) per irRECIST.	Up to 2 years
Secondary	Part 2B: Overall survival	The time from date of first dose of study treatment to the date of death by any cause.	Up to 2 years
Secondary	Part 1: Area under the concentration-time curve from time 0 to last (AUC,0-last) assessment of dostarlimab	Blood samples for determination of serum levels of dostarlimab will be collected.	Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504 and 672 hours post dose
Secondary	Part 1: Area under the concentration-time curve from time 0 to infinity (AUC, 0-infinity) of dostarlimab	Blood samples for determination of serum levels of dostarlimab will be collected.	Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504,672 hours post dose
Secondary	Part 1: Minimum concentration (Cmin) of dostarlimab	Blood samples for determination of serum levels of dostarlimab will be collected.	Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504,672 hours post dose
Secondary	Part 1: Maximum concentration (Cmax) of dostarlimab	Blood samples for determination of serum levels of dostarlimab will be collected.	Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504,672 hours post dose
Secondary	Part 1: Clearance (CL) of dostarlimab	Blood samples for determination of serum levels of dostarlimab will be collected.	Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504,672 hours post dose
Secondary	Part 1: Volume of distribution (Vz) of dostarlimab	Blood samples for determination of serum levels of dostarlimab will be collected.	Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504,672 hours post dose
Secondary	Part 1: Area under the concentration-time curve at steady state (AUC,ss) of dostarlimab	Blood samples for determination of serum levels of dostarlimab will be collected.	Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504,672 hours post dose
Secondary	Part 1: Minimum concentration at steady state (Cmin,ss) of dostarlimab	Blood samples for determination of serum levels of dostarlimab will be collected.	Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504,672 hours post dose.
Secondary	Part 1: Maximum concentration at steady state (Cmax,ss) of dostarlimab	Blood samples for determination of serum levels of dostarlimab will be collected.	Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504,672 hours post dose
Secondary	Part 2A : AUC,0-last assessment of dostarlimab	Blood samples for determination of serum levels of dostarlimab will be collected.	Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, and 504 hours post dose Q3W upto 2 years
Secondary	Part 2A: AUC, 0-infinity of dostarlimab	Blood samples for determination of serum levels of dostarlimab will be collected.	Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, and 504 hours post dose Q3W upto 2 years
Secondary	Part 2A: Cmin of dostarlimab	Blood samples for determination of serum levels of dostarlimab will be collected	Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, and 504,hours post dose Q3W upto 2 years
Secondary	Part 2A: Cmax of dostarlimab	Blood samples for determination of serum levels of dostarlimab will be collected.	Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, and 504,hours post dose Q3W upto 2 years
Secondary	Part 2A: CL of dostarlimab	Blood samples for determination of serum levels of dostarlimab will be collected.	Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, and 504,hours post dose Q3W upto 2 years
Secondary	Part 2A: Vz of dostarlimab	Blood samples for determination of serum levels of dostarlimab will be collected.	Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, and 504 hours post dose Q3W upto 2 years.
Secondary	Part 2A: AUC,ss of dostarlimab	Blood samples for determination of serum levels of dostarlimab will be collected.	Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, and 504 hours post dose Q3W upto 2 years
Secondary	Part 2A: Cmin,ss of dostarlimab	Blood samples for determination of serum levels of dostarlimab will be collected.	Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, and 504 hours post dose Q3W upto 2 years
Secondary	Part 2A: Cmax,ss of dostarlimab	Blood samples for determination of serum levels of dostarlimab will be collected.	Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, and 504 hours post dose Q3W upto 2 years
Secondary	Part 2A : AUC,0-last assessment of dostarlimab	Blood samples for determination of serum levels of dostarlimab will be collected.	Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504, 672, 840, and 1008 hours post dose Q6W upto 2 years
Secondary	Part 2A: AUC, 0-infinity of dostarlimab	Blood samples for determination of serum levels of dostarlimab will be collected.	Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504, 672, 840, and 1008 hours post dose Q6W upto 2 years
Secondary	Part 2A: Cmin of dostarlimab	Blood samples for determination of serum levels of dostarlimab will be collected.	Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504, 672, 840, and 1008 hours post dose Q6W upto 2 years
Secondary	Part 2A: Cmax of dostarlimab	Blood samples for determination of serum levels of dostarlimab will be collected.	Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504, 672, 840, and 1008 hours post dose Q6W upto 2 years
Secondary	Part 2A: CL of dostarlimab	Blood samples for determination of serum levels of dostarlimab will be collected.	Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504, 672, 840, and 1008 hours post dose Q6W upto 2 years
Secondary	Part 2A: Vz of dostarlimab	Blood samples for determination of serum levels of dostarlimab will be collected.	Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504, 672, 840, and 1008 hours post dose Q6W upto 2 years
Secondary	Part 2A: AUC,ss of dostarlimab	Blood samples for determination of serum levels of dostarlimab will be collected.	Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504, 672, 840, and 1008 hours post dose Q6W upto 2 years
Secondary	Part 2A: Cmin,ss of dostarlimab	Blood samples for determination of serum levels of dostarlimab will be collected.	Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504, 672, 840, and 1008 hours post dose Q6W upto 2 years
Secondary	Part 2A: Cmax,ss of dostarlimab	Blood samples for determination of serum levels of dostarlimab will be collected.	Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504, 672, 840 and 1008 hours post dose Q6W upto 2 years
Secondary	Part 2B : AUC,0-last assessment of dostarlimab	Blood samples for determination of serum levels of dostarlimab will be collected.	Predose, 0.5 and 1.5 hours post dose
Secondary	Part 2B: AUC, 0-infinity of dostarlimab	Blood samples for determination of serum levels of dostarlimab will be collected.	Predose, 0.5 and 1.5 hours post dose
Secondary	Part 2B: Cmin of dostarlimab	Blood samples for determination of serum levels of dostarlimab will be collected.	Predose, 0.5 and 1.5 hours post dose
Secondary	Part 2B: Cmax of dostarlimab	Blood samples for determination of serum levels of dostarlimab will be collected.	Predose, 0.5 and 1.5 hours post dose
Secondary	Part 2B: CL of dostarlimab	Blood samples for determination of serum levels of dostarlimab will be collected.	Predose, 0.5 and 1.5 hours post dose
Secondary	Part 2B: Vz of dostarlimab	Blood samples for determination of serum levels of dostarlimab will be collected.	Predose, 0.5 and 1.5 hours post dose
Secondary	Part 2B: AUC,ss of dostarlimab	Blood samples for determination of serum levels of dostarlimab will be collected.	Predose, 0.5 and 1.5 hours post dose
Secondary	Part 2B: Cmin,ss of dostarlimab	Blood samples for determination of serum levels of dostarlimab will be collected.	Predose, 0.5 and 1.5 hours post dose
Secondary	Part 2B: Cmax,ss of dostarlimab	Blood samples for determination of serum levels of dostarlimab will be collected.	Predose, 0.5 and 1.5 hours post dose