A Study of Dazostinag as Single Agent and Dazostinag in Combination With Pembrolizumab in Adults With Advanced or Metastatic Solid Tumors

Solid Neoplasms Clinical Trial

— iintune-1  

Official title:

An Open-label, Dose Escalation, Phase 1/2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of TAK-676 as a Single Agent and in Combination With Pembrolizumab in Adult Patients With Advanced or Metastatic Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04420884
• Other study ID #: TAK-676-1002
• Secondary ID: U1111-1241-44272
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: July 22, 2020
• Est. completion date: January 15, 2026

Study information

• Verified date: June 2024
• Source: Takeda
• Contact: Takeda Contact
• Phone: +1-877-825-3327
• Email: medinfoUS[@]takeda.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main aim of this study is to check if people with advanced solid tumors have side effects from dazostinag, and to check how much dazostinag they can receive without getting significant side effects from it when given alone and in combination with pembrolizumab. The study will be conducted in two phases including a dose escalation phase and a dose expansion phase. In the dose escalation phase, escalating doses of dazostinag are being tested alone and in combination with pembrolizumab to treat participants who have advanced or metastatic solid tumors. In the dose expansion phase, dazostinag will be studied with pembrolizumab with or without chemotherapy in participants with untreated metastatic or recurrent, unresectable squamous cell carcinoma of head and neck (SCCHN) and in combination with pembrolizumab in third-line or later recurrent locally advanced or metastatic microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) and third-line recurrent locally advanced or metastatic microsatellite stable/mismatch repair proficient (MSS/pMMR) colorectal cancer (CRC).

Description:

The drug being tested in this study is called dazostinag. Dazostinag is being tested to treat people who have advanced or metastatic solid tumors.

The study will enroll approximately 368 participants. Part 1 consists of an initial Safety Lead-in to Dose Escalation Phase; Part 2 and Part 3 compose the Expansion Phase in 2 specific indications namely, previously untreated metastatic or recurrent, unresectable SCCHN (Part 2) and third-line or later recurrent locally advanced or metastatic MSI-H/dMMR and third-line recurrent locally advanced or metastatic MSS/pMMR CRC (Part 3). Participants will be assigned to the following treatment groups in the respective Phases of the study:

• Part 1 (Dose Escalation Phase): Safety Lead-in + Dazostinag single agent (SA) [Part 1A] Dazostinag 0.1 milligram (mg) in the Safety Lead-in followed by Dazostinag as escalating doses (0.2 mg and above) in Part 1A

• Part 1B (Combination Dose Escalation Phase): Dazostinag as escalating doses (0.2 mg and above) + Pembrolizumab

• Japan Safety Lead-in: Dazostinag SA 5.0 mg in the Safety Lead-in+ Pembrolizumab. Additional dose levels of Dazostinag (such as 3.5 mg or 7.0 mg and higher) in combination with pembrolizumab may be explored during the Japan safety lead-in considering recommended dose for expansion (RDE1) as 5.0 mg and dose optimization.

Once a safe dose is recommended from Part 1, participants of select advanced or metastatic solid tumors will receive dazostinag in below defined cohorts in the expansion phase:

• Part 2A (SCCHN Combined Positive Score [CPS] ≥ 1 Dose Expansion Phase): Dazostinag + Pembrolizumab*

• Part 2B (SCCHN Dose Expansion Phase): Dazostinag + Pembrolizumab + Chemotherapy

• Part 3A (Expansion Phase in CRC): Dazostinag + Pembrolizumab in MSI-H/dMMR CRC

• Part 3B (Expansion Phase in CRC): Dazostinag + Pembrolizumab in MSS/pMMR CRC* *Dose optimization will be performed in either Part 2A SCCHN or Part 3B CRC.

This multi-center trial will be conducted worldwide. The overall time to participate in this study is 62.9 months. Participants will make multiple visits to the clinic, including 30 days after last dose of study drug for a follow-up assessment. Participants in Parts 2 and 3 will be followed for survival for up to 12 months after the last dose of study drug.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 368
• Est. completion date: January 15, 2026
• Est. primary completion date: January 15, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

2. Dazostinag SA (dose escalation Part 1A):

o With histologically confirmed (cytological diagnosis is acceptable) advanced or metastatic solid tumors that have no standard therapeutic options or are intolerant to these therapies.

3. Dazostinag in combination with pembrolizumab (dose escalation Parts 1B and Japan safety lead-in):

• With histologically confirmed (cytological diagnosis is acceptable) advanced or metastatic solid tumors that have no standard therapeutic options or are intolerant to them, including:

• Tumors that have relapsed or are refractory to anti-programmed cell death ligand protein 1 (anti PD-(L)-1) therapy.

• Tumors that are naive to anti-PD-(L)-1 therapy.

4. For expansion phase only:

• SCCHN (Part 2):

• Participants with histologically confirmed (cytological diagnosis is acceptable) metastatic or recurrent, unresectable SCCHN that is considered incurable by local therapies. Participants should not have had prior systemic therapy administered in the recurrent or metastatic setting. Systemic therapy which was completed more than 6 months before signing consent if given as part of multimodal treatment of locally advanced disease is allowed.

• Anatomic subsites to be included are oral cavity, oropharynx, hypopharynx, larynx, nasal cavity, and paranasal sinuses (maxillary, ethmoid, sphenoid, and frontal). The exception to this is nasopharyngeal cancer and salivary gland tumors, which will not be included.

• Participants with oropharyngeal cancer or tumors arising in the paranasal sinuses (maxillary, ethmoid, sphenoid, and frontal) must agree to provide archival tissue for human papilloma virus (HPV) testing or if known, HPV testing results (using CINtec® p16 Histology assay is preferred but not required) and a 70% cutoff point must be provided. Alternatively, archival tissue or a fresh excisional or core needle biopsy (>=2 cores) is required for the determination of HPV status. If HPV status was previously tested using this method (CINtec® p16 Histology assay is preferred but not required), no additional testing is required.

• For Part 2A, tumors must have a PD-L1 CPS =1. Participants must agree to provide fresh tumor biopsy for analysis from a core or excisional biopsy (fine needle aspirate is not sufficient) at screening for PD-L1 CPS assessment by a central laboratory. This specimen may be the diagnostic sample for participants with a new diagnosis of metastatic SCCHN. Participants for whom newly obtained samples cannot be obtained (eg, inaccessible or participant safety concern) may submit an archived specimen only upon agreement from the Sponsor. Archival tissue can be obtained up to 90 days prior to treatment initiation provided there was no other treatment from the time of biopsy until the start of study treatment. For Part 2B, any CPS is eligible but fresh or archival tissue is required for confirmation of CPS status.

• For Part 2B, participants must be eligible to receive treatment with either cisplatin or carboplatin in combination with 5-fluorouracil (5-FU) per the treating physician.

5. CRC (Part 3):

• Third-line or later MSI-H/dMMR CRC (Part 3A): Participants with histologically confirmed (cytological diagnosis is acceptable) recurrent locally advanced or metastatic MSI-H/dMMR CRC whose disease has progressed on or following therapy with 1) an anti-PD-1 or PD-L1 antibody (i.e., pembrolizumab) and 2) at least one line of combination chemotherapy including a fluoropyrimidine and irinotecan OR oxaliplatin with or without an anti-epidermal growth factor receptor (EGFR) or anti-vascular endothelial growth factor (VEGFR) monoclonal antibody (i.e., cetuximab or bevacizumab). MSI-H/dMMR CRC participants must have received at least 6 weeks of prior treatment with an anti-PD-(L)-1 antibody. Only one line of anti-PD-(L)-1 is permitted.

• Third-line MSS/pMMR CRC (Part 3B): Participants with histologically confirmed (cytological diagnosis is acceptable) recurrent locally advanced or metastatic MSS/pMMR CRC whose disease has progressed on or following therapy with 2 different lines of combination chemotherapy, including therapy with a fluoropyrimidine and irinotecan AND therapy with a fluoropyrimidine and oxaliplatin. Both lines of therapy may be given with or without an anti-EGFR or anti-VEGFR monoclonal antibody (i.e., cetuximab or bevacizumab).

Participants with MSS/pMMR CRC must have progressed on or after combination chemotherapy regimens containing BOTH irinotecan AND oxaliplatin.

• Participants with MSI-H/dMMR or MSS/pMMR CRC must have documented MSI/MMR status assessed by a Clinical Laboratory Improvements Amendment-certified (United States [US] Sites or an accredited (outside of the US) local laboratory using immunohistochemistry (IHC) and/or polymerase chain reaction (PCR) or next generation sequencing (NGS) assay.

• Adequate tumor tissue available for central laboratory confirmation of MSI/MMR status. Note: confirmation of central test positivity is not required before treatment.

• Participants with MSI-H/dMMR or MSS/pMMR CRC must have been treated with 2 prior lines of therapy in the recurrent locally advanced or metastatic setting.

6. Adequate bone marrow, renal, hepatic and cardiac functions.

7. Left ventricular ejection fraction (LVEF) >50%, as measured by echocardiogram or multiple-gated acquisition (MUGA) scan within 4 weeks before receiving the first dose of study drug.

8. Clinically significant toxic effects of previous therapy have recovered to Grade 1 (per NCI CTCAE Version 5.0) or baseline, except for alopecia, Grade 2 peripheral neuropathy, and/or autoimmune endocrinopathies with stable endocrine replacement therapy.

9. In dose escalation Part 1, (not applicable for the Japan safety lead-in) once peripheral evidence of dazostinag pharmacodynamic stimulation of the innate and/or adaptive immune system is observed in the blood and/or an imaging response/partial response (CR/PR) is observed in at least 1 participant, subsequent participants must:

• Have at least 1 lesion amenable for biopsy.

• Agree to have 2 tumor biopsies: 1 during the screening period and 1 while on dazostinag treatment.

10. Must have at least 1 RECIST version 1.1-evaluable (measurable) lesion. For the dose escalation phase (Part 1) only, nonmeasurable only disease is acceptable.

11. Pharmacokinetic (PK)/pharmacodynamic blood must be drawn on a peripherally-inserted catheter. Dazostinag is preferentially administered through a central line, but peripheral infusion is acceptable. If a peripheral line is used for dazostinag and/or pembrolizumab infusion, it must be separate than the one used for PK/pharmacodynamic collection.

Exclusion Criteria:

1. Corrected QT interval by Fredericia (QTcF) greater than (>) 450 milliseconds (men) or >475 milliseconds (women) on a 12-lead electrocardiogram (ECG) during the screening period.

2. Grade greater than or equal to (>=) 2 hypotension (that is, hypotension for which nonurgent intervention is required) at screening or during Cycle 1 Day 1 (C1D1) predose assessment.

3. Oxygen saturation less than (<) 92 percent (%) on room air at screening or during C1D1 predose assessment.

4. Treated with other STING agonists/antagonist and toll-like receptors agonists within the past 6 months.

5. Current history of pneumonitis, interstitial lung disease, severe chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, other restrictive lung diseases, acute pulmonary embolism, or Grade >=2 pleural effusion or ascites not controlled by tap or requiring indwelling catheters.

6. History of brain and leptomeningeal metastasis unless:

• Brain metastases are clinically and radiologically stable or improved (that is, >=6 weeks) following surgery, whole-brain radiation, or stereotactic radiosurgery, AND

• Off corticosteroids.

7. Ongoing Grade >= 2 infection or participants with Grade >=2 fever of malignant origin.

8. Chronic, active hepatitis (example: participants with known hepatitis B surface antigen seropositive and/or detectable hepatitis C virus [HCV]-RNA).

9. For participants in the dose escalation SA Part 1A only: refusal of standard therapeutic options.

10. For participants receiving pembrolizumab only: contraindication and/or intolerance to the administration of pembrolizumab.

11. For participants receiving chemotherapy in Part 2B: contraindication and/or intolerance to the administration of both platinum agents (cisplatin and carboplatin) and/or 5-FU.

12. Participant has had any other prior or concurrent malignancy within 2 years prior to enrollment with the following exceptions: adequately treated localized basal cell or squamous cell carcinoma, or curatively treated in situ carcinoma of the cervix or breast. Other exceptions may be considered upon sponsor consultation.

13. Concurrent chemotherapy (except for Part 2B), immunotherapy (except for pembrolizumab in Part 1B, Part 2, and Part 3), biologic, or hormonal therapy (except for adjuvant endocrine therapy for a history of breast cancer). Concurrent use of hormones for noncancer-related conditions is acceptable (except for corticosteroid hormones) unless allowed per exclusion criterion 16.

14. Radiation therapy within 14 days (42 days for radiation to the lungs) and/or systemic treatment with radionuclides within 42 days before C1D1 of study drug(s). Participants with clinically relevant ongoing pulmonary complications from prior radiation therapy are not eligible.

15. Use of systemic corticosteroids or other immunosuppressive therapy, concurrently or within 7 days of C1D1 of study drug(s), with the following exceptions:

• Topical, intranasal, inhaled, ocular, intra-articular, and/or other non-systemic corticosteroids.

• Premedications required for computed tomography (CT) or magnetic resonance imaging (MRI) scans.

• Physiological doses of replacement steroid therapy (example: for adrenal insufficiency).

• For participants enrolled in Part 2B, chemotherapy premedication with steroids can be administered according to local standards of care practice.

16. Use of medications that are known clinical organic anion-transporting polypeptide B1 (OATP1B1) and/or OATP1B3 inhibitors, concurrently or within 14 days of C1D1 of study drug(s).

17. Receipt of live attenuated vaccine (eg, tuberculosis Bacillus Calmette-Guerin vaccine, oral polio vaccine, measles, rotavirus, yellow fever) within 28 days of C1D1 of study drug(s).

18. Recipients of allogeneic or autologous stem cell transplantation or organ transplantation.

For Part 2 SCCHN only:

19. Has progressive disease (PD) within 6 months of completion of curatively intended systemic treatment for locoregionally advanced SCCHN.

20. Has a life expectancy of less than 3 months and/or has rapidly PD (eg, tumor bleeding, uncontrolled tumor pain) in the opinion of the treating investigator.

21. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 or anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) agent.

22. Participants with known dihydropyrimidine dehydrogenase (DPD) deficiency or thymidine phosphorylase gene (TYMP) mutations (Part 2B only).

Related Conditions & MeSH terms

• Solid Neoplasms

Intervention

Drug:
• Dazostinag
Dazostinag intravenous Infusion.
• Pembrolizumab
Pembrolizumab intravenous Infusion.
• Platinum
Carboplatin or Cisplatin intravenous infusion
• 5-fluorouracil
5-fluorouracil intravenous infusion

Locations

Country	Name	City	State
Austria	Landeskrankenhaus Salzburg	Salzburg
Austria	Klinikum Wels-Grieskirchen	Wels	Oberoesterreich
Austria	Landesklinikum Wiener Neustadt	Wiener Neustadt
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Belgium	Universitair Ziekenhuis Leuven - Campus Gasthuisberg	Leuven
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	McMaster University Medical Center	Hamilton	Ontario
Canada	Jewish General Hospital	Montreal	Quebec
Canada	McGill University Health Centre	Montreal	Quebec
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
China	Beijing Cancer Hospital	Beijing	Beijing Sheng
China	West China Hospital	Chengdu	Sichuan
China	West China School of Medicine - West China Hospital of Sichuan University	Chengdu	Sichuan Sheng
China	Sixth Affiliated Hospital of Sun Yat-Sen University/Guangdong Gastrointestinal Hospital	Guangzhou	Guangzhou Sheng
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai
China	Shanghai East Hospital	Shanghai	Shanghai
France	Centre Hospitalier Regional et Universitaire de Besancon - Hopital Jean-Minjoz	Besancon
France	Hopital Saint-Andre	Bordeaux
France	Centre Francois Baclesse	Caen
France	Centre Georges Francois Leclerc	Dijon
France	Centre de Lutte contre le Cancer - Centre Oscar Lambret	Lille
France	Centre Leon Berard	Lyon
France	Hopital de la Timone	Marseille
France	Hopital Saint-Antoine	Paris
France	Institut de Cancerologie de lOuest - Saint-Herblain - Site Rene Gauducheau	St Herblain
France	Hopital Foch	Suresnes	Ile-de-France
France	Institut de Cancerologie de Lorraine	Vandœuvre-les-Nancy	Meurthe-et-Moselle
France	Gustave Roussy	Villejuif
Israel	Soroka Medical Center	Beer Sheva
Israel	Hadassah University Hospital Ein Kerem	Jerusalem
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv-Yafo
Israel	The Chaim Sheba Medical Center	Tel Hashomer
Japan	National Cancer Center Hospital	Chuo-Ku	Tokyo
Poland	Centrum Onkologii Im. Prof. F. Lukaszczyka w Bydgoszczy	Bydgoszcz	Kujawsko-Pomorskie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy	Warsaw	Mazowieckie
Puerto Rico	Fundacion de Investigacion de Diego	San Juan
Puerto Rico	PanOncology Trials: Universidad de Puerto Rico - Centro Comprensivo de Cancer	San Juan
Puerto Rico	PRCCI Site: Puerto Rico Medical Research Center Torre Medica Hospital Auxilio Mutuo	San Juan
Switzerland	Inselspital Universitatsspital Bern	Bern
Switzerland	Hopitaux Universitaires de Geneve	Geneve
Switzerland	Centre Hospitalier Universitaire Vaudois Lausanne	Lausanne
Switzerland	Kantonsspital Sankt Gallen	St. Gallen	Saint Gallen
United Kingdom	Queen's University Belfast	Belfast	Northern Ireland
United Kingdom	Leeds Teaching Hospitals NHS Trust	Leeds
United Kingdom	The Royal Marsden NHS Foundation Trust	London
United Kingdom	University College London Hospitals NHS Foundation Trust	London
United Kingdom	Oxford University Hospitals NHS Foundation Trust	Oxford
United Kingdom	The Royal Marsden NHS Foundation Trust	Sutton	London
United States	University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center	Baltimore	Maryland
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Robert H. Lurie Comprehensive Cancer Center of Northwestern University	Chicago	Illinois
United States	University of Cincinnati Health Barrett Cancer Center	Cincinnati	Ohio
United States	University of Cincinnati Health Barrett Cancer Center	Cincinnati	Ohio
United States	Siteman Cancer Center - West County	Creve Coeur	Missouri
United States	Mary Crowley Cancer Research	Dallas	Texas
United States	SCRI - HealthOne Denver	Denver	Colorado
United States	Barbara Ann Karmanos Cancer Institute - Lawrence and Idell Weisberg Cancer Treatment Center	Detroit	Michigan
United States	Virginia Cancer Specialists, P.C. - Fairfax	Fairfax	Virginia
United States	Siteman Cancer Center - North County	Florissant	Missouri
United States	Memorial Cancer Institute at Memorial Hospital West - Cancer Institute/Radiology Oncology	Gainesville	Florida
United States	University of California San Diego Moores Cancer Center	La Jolla	California
United States	Norris Comprehensive Cancer Center	Los Angeles	California
United States	Sarah Cannon Research Institute (SCRI)	Nashville	Tennessee
United States	Yale Cancer Center	New Haven	Connecticut
United States	UCI Health - Chao Family Comprehensive Cancer Center	Orange	California
United States	Orlando Health Cancer Institute	Orlando	Florida
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Providence Portland Medical Center	Portland	Oregon
United States	Siteman Cancer Center - South County	Saint Louis	Missouri
United States	Washington University School of Medicine Siteman Cancer Center	Saint Louis	Missouri
United States	Siteman Cancer Center - St. Peters	Saint Peters	Missouri
United States	University of California Los Angeles - Jonsson Comprehensive Cancer Center	Santa Monica	California
United States	West Chester Hospital	West Chester	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  China,  France,  Israel,  Japan,  Poland,  Puerto Rico,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Reporting one or More Treatment-emergent Adverse Events (TEAEs) and Based on TEAEs Severity	A severity grade is defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0. Grade 1 scales as Mild (asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated); Grade 2 scales as Moderate (minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living [ADL]); Grade 3 scales as Severe (severe or medically significant but not immediately life threatening hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL); Grade 4 scales as Life-threatening consequences, urgent intervention indicated, and Grade 5 scales as Death related to Adverse Event (AE).	Up to approximately 54 months
Primary	Number of Participants with Dose-Limiting Toxicities (DLTs)	A DLT will be defined as any of the TEAEs, but not limited to, those that occur during Cycle 1 and are considered by the investigator to be at least possibly related to dazostinag as a single agent (SA) or in combination with pembrolizumab. TEAEs meeting DLT definitions occurring in Cycle 2 or later will be considered in the determination of the RDE of dazostinag, both in the dazostinag SA and the combination with pembrolizumab arms. Toxicity will be evaluated according to NCI CTCAE version 5.0.	Up to approximately 54 months
Primary	Number of Participants Reporting One or More Treatment Emergent Serious Adverse Event (SAEs)		Up to approximately 54 months
Primary	Number of Participants With one or More TEAEs Leading to Dose Modifications and Treatment Discontinuations		Up to approximately 54 months
Secondary	Dose Escalation, Japan Safety Lead-in, and Expansion Phases: Cmax: Maximum Observed Plasma Concentration for Dazostinag		Dose Escalation, Japan Safety Lead-in, and Expansion Phases: Cycle 1 Days 1, 8 and 15: pre-infusion and at multiple time points (up to 24 hours) post-infusion and at Day 1 for further cycles up to 54 months (Cycle length=21 days)
Secondary	Dose Escalation, Japan Safety Lead-in, and Expansion Phases: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Dazostinag		Dose Escalation, Japan Safety Lead-in, and Expansion Phases: Cycle 1 Days 1, 8 and 15: pre-infusion and at multiple time points (up to 24 hours) post-infusion and at Day 1 for further cycles up to 54 months (Cycle length=21 days)
Secondary	Dose Escalation, Japan Safety Lead-in, and Expansion Phases: AUCt: Area Under the Concentration-time Curve From Time 0 to Time t for Dazostinag		Dose Escalation, Japan Safety Lead-in, and Expansion Phases: Cycle 1 Days 1, 8 and 15: pre-infusion and at multiple time points (up to 24 hours) post-infusion and at Day 1 for further cycles up to 54 months (Cycle length=21 days)
Secondary	Dose Escalation, Japan Safety Lead-in, and Expansion Phases: AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity for Dazostinag		Dose Escalation, Japan Safety Lead-in, and Expansion Phases: Cycle 1 Days 1, 8 and 15: pre-infusion and at multiple time points (up to 24 hours) post-infusion and at Day 1 for further cycles up to 54 months (Cycle length=21 days)
Secondary	Dose Escalation, Japan Safety Lead-in, and Expansion Phases: t1/2z: Terminal Disposition Phase Half-life for Dazostinag		Dose Escalation, Japan Safety Lead-in, and Expansion Phases: Cycle 1 Days 1, 8 and 15: pre-infusion and at multiple time points (up to 24 hours) post-infusion and at Day 1 for further cycles up to 54 months (Cycle length=21 days)
Secondary	Dose Escalation, Japan Safety Lead-in, and Expansion Phases: CL: Total Clearance After Intravenous Administration for Dazostinag		Dose Escalation, Japan Safety Lead-in, and Expansion Phases: Cycle 1 Days 1, 8 and 15: pre-infusion and at multiple time points (up to 24 hours) post-infusion and at Day 1 for further cycles up to 54 months (Cycle length=21 days)
Secondary	Dose Escalation, Japan Safety Lead-in, and Expansion Phases: Vss: Volume of Distribution at Steady State After Intravenous Administration for Dazostinag		Dose Escalation, Japan Safety Lead-in, and Expansion Phases: Cycle 1 Days 1, 8 and 15: pre-infusion and at multiple time points (up to 24 hours) post-infusion and at Day 1 for further cycles up to 54 months (Cycle length=21 days)
Secondary	Dose Escalation, Japan Safety Lead-in, and Expansion Phases: CLR: Renal Clearance for Dazostinag		Dose Escalation, Japan Safety Lead-in, and Expansion Phases: Cycle 1 Days 1, 8 and 15: pre-infusion and at multiple time points (up to 24 hours) post-infusion and at Day 1 for further cycles up to 54 months (Cycle length=21 days)
Secondary	Dose Escalation, Japan Safety Lead-in, and Expansion Phases: Percentage of Dose Excreted in Urine During 24 Hours After Dosing		Dose Escalation, Japan Safety Lead-in, and Expansion Phases: Cycle 1 Days 1, 8 and 15: pre-infusion and at multiple time points (up to 24 hours) post-infusion and at Day 1 for further cycles up to 54 months (Cycle length=21 days)
Secondary	Dose Escalation, Japan Safety Lead-in, and Expansion Phases: CLR/CL%: Renal Clearance as Percentage of Total Clearance for Dazostinag		Dose Escalation, Japan Safety Lead-in, and Expansion Phases: Cycle 1 Days 1, 8 and 15: pre-infusion and at multiple time points (up to 24 hours) post-infusion and at Day 1 for further cycles up to 54 months (Cycle length=21 days)
Secondary	Dose Escalation Phase: Percentage of Dose Excreted in Feces During 24 Hours After Dosing		Dose Escalation Phase: Cycle 1 Day 1: from start of infusion and at multiple time points (up to 24 hours) post-infusion (Cycle length=21 days)
Secondary	Dose Escalation, Japan Safety Lead-in, and Expansion Phases: Overall Response Rate (ORR)	ORR is defined as the percentage of participants who achieve confirmed complete response (cCR) + confirmed partial response (cPR) during the study in response-evaluable population. ORR will be assessed based on Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1.	Up to approximately 54 months
Secondary	Dose Escalation, Japan Safety Lead-in, and Expansion Phases: Disease Control Rate (DCR)	DCR is defined as the percentage of participants who achieve cCR + cPR + stable disease (SD) greater than (>) 6 weeks during the study in response-evaluable population. The DCR will be assessed based on RECIST version 1.1.	Up to approximately 54 months
Secondary	Dose Escalation, Japan Safety Lead-in, and Expansion Phases: Duration of Response (DOR)	DOR is the time from the date of first documentation of a cPR or better to the date of first documentation of progressive disease for responders (cPR or better). Responders without documentation of progressive disease will be censored at the date of last response assessment that is SD or better. DOR will be assessed based on RECIST version 1.1.	Up to approximately 54 months
Secondary	Dose Escalation, Japan Safety Lead-in, and Expansion Phases: Time to Response (TTR)	TTR is defined as the time from the date of first dose administration to the date of first documented cPR or better by the investigator. TTR will be assessed based on RECIST version 1.1.	Up to approximately 54 months
Secondary	Dose Escalation, Japan Safety Lead-in, and Expansion Phases: Fold Change from Baseline in Upregulation of Dazostinag-induced Stimulator of Interferon Genes (STING)		Baseline up to Month 54
Secondary	Dose Escalation, Japan Safety Lead-in, and Expansion Phases: Fold Change from Baseline in T-cell Infiltration Upon Dazostinag Treatment		Baseline up to Month 54
Secondary	Dose Escalation, Japan Safety Lead-in, and Expansion Phases: Fold Change from Baseline of Genomic, Transcriptomic and Protein Expressions in Tumor Tissues		Baseline up to Month 54
Secondary	Expansion Phase Only: Progression-Free Survival (PFS)	PFS is defined as the time from the date of first dose administration to the date of first documented disease progression or death due to any cause, whichever occurs first.	Up to approximately 24 months
Secondary	Expansion Phase Only: Overall Survival (OS)	OS is defined as the time from the date of first dose administration to the date of death.	Up to approximately 24 months
Secondary	Expansion Phase Only: OS Rate at 12 Months	12-month OS rate is defined as the percentage of participants who are still alive at 12 months from their first dose administration.	Up to 24 months
Secondary	Expansion Phase Only: OS Rate at 6 Months	6-month OS rate is defined as the percentage of participants who are still alive at 6 months from their first dose administration.	Up to 24 months

External Links

•   To obtain more information on the study, click here/on this link