Study of Quavonlimab (MK-1308) in Combination With Pembrolizumab (MK-3475) in Advanced Solid Tumors (MK-1308-001)

Advanced Solid Tumors Clinical Trial

Official title:

A Phase 1 / 2 Open Label, Multi-Arm, Multicenter Study of MK-1308 in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03179436
• Other study ID #: 1308-001
• Secondary ID: MK-1308-00117382
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: July 2, 2017
• Est. completion date: April 8, 2024

Study information

• Verified date: April 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will assess the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of escalating doses of quavonlimab when used in combination with pembrolizumab in participants with advanced solid tumors.

Description:

After screening, participants will be assigned to the Dose Escalation, Dose Confirmation, Efficacy Expansion, or Coformulation Phase. The Dose Escalation Phase will evaluate available PK and safety data including dose limiting toxicities (DLTs). The Dose Confirmation Phase will gather additional safety, tolerability, PK, and preliminary efficacy data of quavonlimab in combination with pembrolizumab, and will include first-line advanced/metastatic non-small cell lung cancer (NSCLC) and second line (and beyond) advanced/metastatic small cell lung cancer (SCLC). The purpose of the Efficacy Expansion Phase is to gather preliminary anti-tumor efficacy data for quavonlimab in combination with pembrolizumab as well as for quavonlimab monotherapy in the specific target population of programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) refractory melanoma. The Coformulation Phase will evaluate the safety and PK of a coformulated product of pembrolizumab/quavonlimab (MK-1308A) in comparison to that of the single, co-administered products given at the same dose and schedule, and include participants with advanced solid tumors and participants from mainland China.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 413
• Est. completion date: April 8, 2024
• Est. primary completion date: April 8, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

For Dose Escalation Phase:

• Have any histologically- or cytologically-confirmed advanced/metastatic solid tumor (except NSCLC for Cohorts 2 and 3) by pathology report and have received, been intolerant to, been ineligible for, or refused all treatment known to confer clinical benefit

For Dose Confirmation Phase NSCLC Arms (A, B, C, and E):

• Have newly diagnosed histologically or cytologically-confirmed stage IIIB/stage IV NSCLC. Epidermal growth factor receptor (EGFR)-and anaplastic lymphoma kinase (ALK) translocation-directed therapy is not indicated as primary therapy. Participant must not have received prior systemic treatment for advanced NSCLC or must have received previous neoadjuvant and adjuvant chemotherapies =6 months before dosing of study drug if prior systemic treatment was given for early stage disease

For Dose Confirmation Phase SCLC Arm (Arm D):

• Have histologically- or cytologically-confirmed metastatic (Stage III/IV) SCLC with progressive disease after =1 platinum-based chemotherapy regimen. Participants with platinum-sensitive disease are eligible

• Have measurable disease by RECIST 1.1 as assessed by the local site investigator/radiology

• Have Eastern Cooperative Oncology Group (ECOG) Performance Scale status of 0 or 1

• A female participant is eligible to participate if she is not pregnant or breastfeeding and at least 1 of the following conditions applies:

• Is not a woman of child bearing potential (WOCBP) OR

• Is a WOCBP and using a contraceptive method that is highly effective during the intervention period and for at least 120 days after the last dose of pembrolizumab or pembrolizumab/quavonlimab, whichever comes last

• Female participants of childbearing potential must have negative urine or serum pregnancy test within 24 hours for urine and within 72 hours for serum prior to receiving the first dose of study treatment

• Male participants with a female partner(s) of child-bearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication and refrain from donating sperm during this period

• Must submit an evaluable baseline tumor sample for analysis (either a recent or archival tumor sample)

For Efficacy Expansion Phase Arms F and G:

• Have histologically/cytologically-confirmed unresectable Stage III or Stage IV melanoma per American Joint Committee on Cancer (AJCC) staging system version 8, not amenable to local therapy

• Have at least 1 measurable lesion by CT or MRI per RECIST 1.1 by BICR. Cutaneous lesions and other superficial lesions are not considered measurable lesions for the purposes of this protocol, but may be considered as non-target lesions

• Participants with unresectable Stage III or IV disease must have progressed on treatment with an anti-PD-1/L1 monoclonal antibody (mAb) administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies (combinations with anti-cytotoxic T-lymphocyte associated protein 4 [CTLA-4] agents will not be allowed)

• Participants who receive anti-PD-1 therapy as adjuvant treatment following complete resection of Stage III or IV melanoma and have disease recurrence (unresectable loco-regional disease or distant metastases) while on active treatment or within 6 months of stopping anti-PD-1 are eligible

• Have submitted pre-trial imaging and provided a baseline tumor sample

• Proto-oncogene B-raf (BRAF) V600 mutation-positive melanoma participants should have received targeted therapy for advanced or metastatic disease (eg, BRAF/MEK inhibitor, alone or in combination) prior to enrolling on this study; however, they are not required to progress on this treatment prior to enrollment

• BRAF V600E mutation-positive melanoma participants who have NOT received a BRAF inhibitor (either as adjuvant therapy or in the metastatic disease setting) with lactate dehydrogenase (LDH) < local upper limit of normal (ULN), no clinically significant tumor-related symptoms, and absence of rapidly progressing metastatic melanoma. Approximately 10 participants each from Arms F and G will have 2 mandatory biopsies

For Dose Coformulation Phase Arm I:

• Have any histologically- or cytologically-confirmed advanced/metastatic solid tumor by pathology report and have received, been intolerant to, been ineligible for or refused all treatment known to confer clinical benefit

• Meet all requirements for Dose Escalation Phase and Dose Confirmation Phase

For the Coformulation Phase - Arm K (China only):

• Have any histologically- or cytologically-confirmed advanced/metastatic solid tumor by pathology report and have received, been intolerant to, been ineligible for, or refused all treatment known to confer clinical benefit

• Be a Chinese participant residing in China.

Exclusion Criteria:

• For all phases of the study: Has received previous treatment with another agent targeting cytotoxic T lymphocyte leukocyte antigen (CTLA)-4

For Dose Confirmation Phase:

• Has received previous treatment with another agent targeting programmed cell death protein 1 (PD-1), programmed cell death ligand 1 (PD-L1), or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor

• Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) prior to the first dose of study therapy, or has not recovered to Common Toxicity Criteria for Adverse Events (CTCAE) Grade 1 or better from any AEs that were due to cancer therapeutics administered more than 4 weeks earlier

• Has received lung radiation therapy of >30 Gray (Gy) within 6 months before the first dose of study treatment

• Is currently participating and receiving study therapy in a study of an investigational agent or has participated and received study therapy in a study of an investigational agent or has used an investigational device within 28 days of administration of quavonlimab.

• Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years

For Dose Escalation Cohorts (1-3) and Dose Confirmation Arms (A-E):

• Has known untreated central nervous system (CNS) metastases. Has known carcinomatous meningitis

• Has received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse events (irAE)

• Has had a severe hypersensitivity reaction to treatment with any monoclonal antibody or components of the study drug

• Has any active infection requiring therapy

• Has a history of interstitial lung disease, history of noninfectious pneumonitis that required steroids (or has current pneumonitis), or history of inflammatory bowel disease

• Has an active autoimmune disease that has required systemic treatment in the past 2 years

• Has clinically significant cardiac disease

• Has received a live or live attenuated vaccine within 28 days of planned treatment start

• Has known history of human immunodeficiency virus (HIV) and/or known active Hepatitis B or C infections, and/or known to be positive for hepatitis B surface antigen (HBsAg)/ hepatitis B virus (HBV) DNA

• Has known psychiatric or substance abuse disorders that would interfere with the participant's ability to cooperate with the requirements of the trial

• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with screening and for up to 120 days following cessation of pembrolizumab or pembrolizumab/quavonlimab

• Has not fully recovered from any effects of major surgery without significant detectable infection

For Arm F and G (Efficacy Expansion Phase) and Arm K (Coformulation Phase) ONLY:

• Has known active CNS metastases and/or carcinomatous meningitis

• Has not had resolution of anti-PD-1 antibody-related AEs, including immune-mediated AEs back to Grade =1 or baseline (not applicable to Arm K)

• Has not discontinued steroid treatment for an irAE for at least 2 weeks prior to the first dose of study drug (not applicable to Arm K)

• Has ocular melanoma (not applicable to Arm K)

• Has mucosal melanoma (not applicable to Arm K)

• Has had an allogenic tissue/solid organ transplant

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Neoplasms

Intervention

Biological:
• Quavonlimab
Quavonlimab is administered intravenously (IV) during the Dose Escalation Phase and Dose Confirmation Phase at either DL1 or DL2, and is administered IV during the Efficacy Expansion Phase at DL2.
• Pembrolizumab
Pembrolizumab is administered IV at PDL1 on Day 1 of each cycle starting Cycle 2 for the Dose Escalation Phase or starting Cycle 1 of the Dose Confirmation Phase. Pembrolizumab is administered IV at PDL2 on Day 1 of each cycle for the Efficacy Expansion Phase (Arm G).

Drug:
• Pembrolizumab/Quavonlimab
Pembrolizumab/Quavonlimab is a coformulated product composed of quavonlimab at DL1 in combination with pembrolizumab at dose level 2 (PDL2).

Locations

Country	Name	City	State
Australia	Ballarat Health Services ( Site 0022)	Ballarat	Victoria
Australia	Blacktown Hospital. Western Sydney local health district ( Site 0009)	Blacktown	New South Wales
Australia	Gallipoli Medical Research Foundation-GMRF CTU ( Site 0019)	Brisbane	Queensland
Australia	Cairns and Hinterland Hospital and Health Service ( Site 0020)	Cairns	Queensland
Australia	Ashford Cancer Centre Research ( Site 0012)	Kurralta Park	South Australia
Australia	Alfred Health ( Site 0018)	Melbourne	Victoria
Australia	Calvary Mater Newcastle ( Site 0025)	Waratah	New South Wales
Australia	Melanoma Institute Australia ( Site 0017)	Wollstonecraft	New South Wales
Canada	Centre Hospitalier de l Universite de Montreal - CHUM ( Site 1102)	Montreal	Quebec
Canada	Jewish General Hospital ( Site 1105)	Montreal	Quebec
Canada	McGill University Health Centre ( Site 1101)	Montreal	Quebec
Canada	Princess Margaret Cancer Centre ( Site 1104)	Toronto	Ontario
Canada	Sunnybrook Research Institute ( Site 1103)	Toronto	Ontario
Chile	Fundacion Arturo Lopez Perez ( Site 5601)	Santiago	Region M. De Santiago
China	Beijing Cancer hospital-Digestive Oncology ( Site 5001)	Beijing	Beijing
China	Chongqing Cancer Hospital-Phase 1 Unite ( Site 5004)	Chongqing	Chongqing
China	Sir Run Run Shaw Hospital-Medical Oncology ( Site 5003)	Hangzhou	Zhejiang
France	Institut Bergonie ( Site 3306)	Bordeaux	Gironde
France	CHRU Lille - Hopital Claude Huriez ( Site 3302)	Lille	Nord
France	Hopital La Timone ( Site 3303)	Marseille	Bouches-du-Rhone
France	CH Lyon Sud Hospices Civils de Lyon ( Site 3307)	Pierre Benite	Rhone
France	Gustave Roussy ( Site 3305)	Villejuif	Val-de-Marne
Greece	Regional General Hospital of Athens "Laiko" ( Site 3001)	Athens	Attiki
Israel	Rambam Medical Center ( Site 0003)	Haifa
Israel	Hadassah Ein Karem Hebrew University Medical Center ( Site 0021)	Jerusalem
Israel	Sheba Medical Center - Cancer Center ( Site 0002)	Ramat-Gan
Italy	Istituto Nazionale Tumori Fondazione Pascale ( Site 3903)	Napoli
Italy	IRCCS Istituto Oncologico Veneto ( Site 3905)	Padova
Italy	Policlinico Le Scotte - A.O. Senese ( Site 3907)	Siena
Japan	Hyogo Cancer Center ( Site 0015)	Akashi	Hyogo
Japan	National Cancer Center Hospital East ( Site 0014)	Kashiwa	Chiba
Korea, Republic of	Samsung Medical Center ( Site 0010)	Seoul
Korea, Republic of	Seoul National University Hospital ( Site 0007)	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System ( Site 0008)	Seoul
Korea, Republic of	Asan Medical Center ( Site 0006)	Seoul.	Seoul
New Zealand	Auckland City Hospital ( Site 0016)	Auckland
New Zealand	Canterbury District Health Board ( Site 0023)	Christchurch	Canterbury
Poland	Szpital Kliniczny im. Heliodora Swiecickiego Uniwers Medyczn ( Site 4803)	Poznan	Wielkopolskie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Oddzial Badan Wczesnych Faz ( Site 4801	Warszawa	Mazowieckie
South Africa	Sandton Oncology Medical Group PTY LTD ( Site 2701)	Johannesburg	Gauteng
South Africa	Cape Town Oncology Trials Pty Ltd ( Site 2704)	Kraaifontein	Western Cape
South Africa	Cancercare Rondebosch Oncology ( Site 2706)	Rondebosch	Western Cape
Spain	Hospital Clinic i Provincial de Barcelona ( Site 3401)	Barcelona
Spain	Instituto Catalan de Oncologia ICO - Hospital Duran i Reynals ( Site 3403)	Hospitalet de Llobregat	Barcelona
Spain	Onkologikoa - Instituto Oncologico de San Sebastian ( Site 3405)	San Sebastian	Gipuzkoa
Spain	Hospital Universitario Virgen de la Macarena ( Site 3402)	Sevilla
Spain	Hospital General Universitario de Valencia ( Site 3404)	Valencia	Valenciana, Comunitat
Sweden	Skanes Universitetssjukhus Lund. ( Site 4601)	Lund	Skane Lan
United States	Inova Schar Cancer Institute ( Site 1001)	Fairfax	Virginia
United States	Banner MD Anderson Cancer Center ( Site 0013)	Gilbert	Arizona
United States	John Theurer Cancer Center at Hackensack University Medical Center ( Site 0005)	Hackensack	New Jersey
United States	Tennessee Oncology Nashville ( Site 0004)	Nashville	Tennessee
United States	South Texas Accelerated Research Therapeutics, LLC (START) ( Site 0001)	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Chile,  China,  France,  Greece,  Israel,  Italy,  Japan,  Korea, Republic of,  New Zealand,  Poland,  South Africa,  Spain,  Sweden, 

References & Publications (2)

Cho BC, Yoh K, Perets R, Nagrial A, Spigel DR, Gutierrez M, Kim DW, Kotasek D, Rasco D, Niu J, Satouchi M, Ahn MJ, Lee DH, Maurice-Dror C, Siddiqi S, Ren Y, Altura RA, Bar J. Anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody quavonlimab — View Citation

Perets R, Bar J, Rasco DW, Ahn MJ, Yoh K, Kim DW, Nagrial A, Satouchi M, Lee DH, Spigel DR, Kotasek D, Gutierrez M, Niu J, Siddiqi S, Li X, Cyrus J, Chackerian A, Chain A, Altura RA, Cho BC. Safety and efficacy of quavonlimab, a novel anti-CTLA-4 antibody — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with a Dose Limiting Toxicity (DLT)	DLTs will be assessed during the first 6 weeks (2 cycles) of treatment for the Dose Escalation and the first 3 weeks (1 cycle) of treatment for the Dose Confirmation. DLT is defined as toxicity that is possibly, probably, or definitely related to study therapy and may result in a change in the given dose. DLTs include Grade (Gr)4 non-hematologic toxicity (not laboratory); Gr 4 hematologic toxicity lasting =7 days (except thrombocytopenia); most non-hematologic AEs = Gr 3 in severity; any Gr 3 or Gr 4 non-hematologic laboratory value that requires clinically significant medical intervention, leads to hospitalization, persists for >1 week, or results in a drug-induced liver injury; Gr 3 or Gr 4 febrile neutropenia; a prolonged delay in initiating Cycle 2 or 3 of Dose Escalation or Cycle 2 of Dose Confirmation due to treatment-related toxicity; any treatment-related toxicity that causes the participant to discontinue treatment during the DLT observation period, and Gr 5 toxicity.	Up to 6 weeks
Primary	Number of participants with =1 adverse event (AE)	An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment.	Up to ~2.5 years
Primary	Number of participants discontinuing study treatment due to an AE	An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment.	Up to ~2 years
Primary	Efficacy Expansion: Number of participants with =1 AE	An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment.	Up to ~2.5 years
Primary	Efficacy Expansion: Number of participants discontinuing study treatment due to an AE	An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment	Up to ~2 years
Primary	Coformulation: Number of participants with =1 DLT	DLTs will be assessed during the first 6 weeks of treatment for the Coformulation Phase (Arm I). A DLT is defined as toxicity that is possibly, probably, or definitely related to study therapy and may result in a change in the given dose. DLTs include Grade (Gr)4 non-hematologic toxicity (not laboratory); Gr 4 hematologic toxicity lasting =7 days (except thrombocytopenia); most non-hematologic AEs = Gr 3 in severity; any Gr 3 or Gr 4 non-hematologic laboratory value that requires clinically significant medical intervention, leads to hospitalization, persists for >1 week, or results in a drug-induced liver injury; Gr 3 or Gr 4 febrile neutropenia; a prolonged delay in initiating Cycle 2 of the Coformulation Phase due to treatment-related toxicity; any treatment-related toxicity that causes the participant to discontinue treatment during the DLT observation period, and Gr 5 toxicity.	Up to 6 weeks
Primary	Coformulation: Number of participants with =1 AE	An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment.	Up to ~2.5 years
Primary	Coformulation: Number of participants discontinuing study treatment due to an AE	An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment.	Up to ~2 years
Primary	Efficacy Expansion: Objective Response Rate (ORR) as assessed by blinded independent central review (BICR) based on adjusted Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)	ORR is defined as the percentage of participants in the analysis population whose best overall response (BOR) is confirmed complete response (CR) or partial response (PR) as assessed by BICR and based on imaging per adjusted RECIST 1.1. Tumor responses evaluated using adjusted RECIST 1.1 follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ and require confirmation per RECIST 1.1. According to adjusted RECIST 1.1, CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR according to adjusted RECIST 1.1 is at least a 30% decrease in the sum of diameters (SOD) of target lesions as assessed by the investigator, taking as reference the baseline SOD.	Up to ~4 years
Secondary	Area under the plasma concentration time curve (AUC) of pembrolizumab	AUC is the area under the plot of plasma concentration of drug against time after drug administration. Blood samples will be collected at multiple time points to assess the AUC of pembrolizumab.	At designated timepoints (up to ~6 months)
Secondary	Maximum concentration (Cmax) of pembrolizumab	Cmax is the maximum or "peak" concentration of a drug observed after its administration. Blood samples will be collected at multiple time points to assess the Cmax of pembrolizumab.	At designated timepoints (up to ~6 months)
Secondary	Minimum concentration (Cmin) of pembrolizumab	Cmin is the minimum or "trough" concentration of a drug observed after its administration and just prior to the administration of a subsequent dose. Blood samples will be collected at multiple time points (pre-dose) to assess the Cmin of pembrolizumab.	At designated timepoints (up to ~6 months)
Secondary	Number of participants with pembrolizumab anti-drug antibodies (ADAs)	Blood samples will be collected at designated time points for the determination of the presence or absence of pembrolizumab ADAs. The number of participants who develop pembrolizumab ADAs will be reported.	At designated timepoints (up to ~2 years)
Secondary	AUC of quavonlimab	AUC is the area under the plot of plasma concentration of drug against time after drug administration. Blood samples will be collected at multiple time points to assess the AUC of quavonlimab.	At designated timepoints (up to ~6 months)
Secondary	Cmax of quavonlimab	Cmax is the maximum or "peak" concentration of a drug observed after its administration. Blood samples will be collected at multiple time points to assess the Cmax of quavonlimab.	At designated timepoints (up to ~6 months)
Secondary	Cmin of quavonlimab	Cmin is the minimum or "trough" concentration of a drug observed after its administration and just prior to the administration of a subsequent dose. Blood samples will be collected at multiple time points (pre-dose) to assess the Cmin of quavonlimab.	At designated timepoints (up to ~6 months)
Secondary	Number of participants with quavonlimab ADAs	Blood samples will be collected at designated time points for the determination of the presence or absence of quavonlimab ADAs. The number of participants who develop quavonlimab ADAs will be reported.	At designated timepoints (up to ~2 years)
Secondary	Chinese Cohort: AUC of pembrolizumab	AUC is the area under the plot of plasma concentration of drug against time after drug administration. Blood samples will be collected at multiple time points to assess the AUC of pembrolizumab.	At designated timepoints (up to ~6 months)
Secondary	Chinese Cohort: Cmax of pembrolizumab	Cmax is the maximum or "peak" concentration of a drug observed after its administration. Blood samples will be collected at multiple time points to assess the Cmax of pembrolizumab.	At designated timepoints (up to ~6 months)
Secondary	Chinese Cohort: Cmin of pembrolizumab	Cmin is the minimum or "trough" concentration of a drug observed after its administration and just prior to the administration of a subsequent dose. Blood samples will be collected at multiple time points (pre-dose) to assess the Cmin of pembrolizumab.	At designated timepoints (up to ~6 months)
Secondary	Chinese Cohort: Number of participants with pembrolizumab ADAs	Blood samples will be collected at designated time points for the determination of the presence or absence of pembrolizumab ADAs. The number of participants who develop pembrolizumab ADAs will be reported.	At designated timepoints (up to ~2 years)
Secondary	Chinese Cohort: AUC of quavonlimab	AUC is the area under the plot of plasma concentration of drug against time after drug administration. Blood samples will be collected at multiple time points to assess the AUC of quavonlimab.	At designated timepoints (up to ~6 months)
Secondary	Chinese Cohort: Cmax of quavonlimab	Cmax is the maximum or "peak" concentration of a drug observed after its administration. Blood samples will be collected at multiple time points to assess the Cmax of quavonlimab.	At designated timepoints (up to ~6 months)
Secondary	Chinese Cohort: Cmin of quavonlimab	Cmin is the minimum or "trough" concentration of a drug observed after its administration and just prior to the administration of a subsequent dose. Blood samples will be collected at multiple time points (pre-dose) to assess the Cmin of quavonlimab.	At designated timepoints (up to ~6 months)
Secondary	Chinese Cohort: Number of participants with quavonlimab ADAs	Blood samples will be collected at designated time points for the determination of the presence or absence of quavonlimab ADAs. The number of participants who develop quavonlimab ADAs will be reported.	At designated timepoints (up to ~2 years)
Secondary	Dose Escalation, Dose Confirmation, Coformulation: ORR as assessed by investigator based on adjusted RECIST v1.1	ORR is defined as the percentage of participants in the analysis population whose BOR is confirmed CR or PR as assessed by investigator and based on imaging per adjusted RECIST 1.1. Tumor responses evaluated using adjusted RECIST 1.1 follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ and require confirmation per RECIST 1.1. According to adjusted RECIST 1.1, CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR according to adjusted RECIST 1.1 is at least a 30% decrease in the SOD of target lesions as assessed by the investigator, taking as reference the baseline SOD.	Up to ~4 years
Secondary	Efficacy Expansion: Duration of Response (DOR) as assessed by BICR based on adjusted RECIST v1.1	DOR is defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first (for responders only).	Up to ~4 years

External Links

•   Merck Clinical Trials Information