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

NCT02715284 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2133464010-01-001
• Study Type: interventional
• Target: 730
• Locations: 10 countries
• Sites: 105

Brief 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.

Conditions

Neoplasms

Keywords

Metastatic solid tumors; Advanced solid tumors; Anti-PD-1; TSR-042; Immunotherapy; PD-1; Endometrial; Non-small cell lung cancer; NSCLC; MSI-High; Dostarlimab; dMMR

Outcome Measures

Primary Outcomes (28)

• 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

• Part 1: Number of participants with immune mediated AEs of interest

  Participants with immune related AEs of interest will be assessed.

  Up to 2 years

• 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

• 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, creatinine, bilirubin, alkaline phosphatase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and albumin.

  Up to 2 years

• Part 1, Part 2A, and Part 2B: Number of participants with a change from baseline in urinalysis parameters

  Number of participants will be assessed.

  Up to 2 years

• Part 1, Part 2A, and Part 2B: Number of participants with a change from baseline in vital signs

  Number of participants will be assessed.

  Up to 2 years

• 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

• Part 1: Number of participants receiving concomitant medications

  Concomitant medications will be recorded.

  Up to 2 years

• 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

• Part 2A: Number of participants with immune mediated AEs of interest

  Participants with immune related AEs of interest will be assessed.

  Up to 2 years

• 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

• 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, creatinine, bilirubin, AST, ALT, and albumin.

  Up to 2 years

• 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

• Part 2A: Number of participants receiving concomitant medications

  Concomitant medications will be recorded.

  Up to 2 years

• 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

• 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

• 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

• 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, creatinine, bilirubin, AST, ALT, and albumin.

  Up to 2 years

• 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

• Part 2B: Number of participants receiving concomitant medications

  Concomitant medications will be recorded.

  Up to 2 years

• 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 evaluated by independent blinded central review using RECIST version 1.1.

  Up to 2 years

• Part 2B: Cohort F ORR by RECIST version 1.1

  ORR is defined as the proportion of participants achieving CR or PR as evaluated by independent blinded central review using RECIST version 1.1.

  Up to 2 years

• Part 2B: Cohort A2 ORR by RECIST version 1.1

  ORR is defined as the proportion of participants achieving CR or PR as evaluated by independent blinded central review using RECIST version 1.1.

  Up to 2 years

• Part 2B: Cohort G ORR by RECIST version 1.1

  ORR is defined as the proportion of participants achieving CR or PR as evaluated by independent blinded central review using RECIST version 1.1.

  Up to 2 years

• 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

• 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

• 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

• 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 Outcomes (49)

• Part 1: Immune-related objective response rate (irORR) by irRECIST

  Up to 2 years

• Part 2B: Cohort A1 ORR by independent blinded central review using RECIST version 1.1

  Up to 2 years

• Part 2B: Cohort F ORR by independent blinded central review using RECIST version 1.1

  Up to 2 years

• Part 2B: Cohort A1 Immune-related objective response rate (irORR) by irRECIST

  Up to 2 years

• Part 2B: Cohort A2 irORR by irRECIST

  Up to 2 years

Study Arms (7)

Part 1: Participants receiving dostarlimab

EXPERIMENTAL

Part 1 will evaluate dostarlimab at ascending weight-based doses 1 mg/kg, 3 mg/kg and 10 mg/kg. Higher dose levels 15 mg/kg and/or 20 mg/kg may also be explored. Dostarlimab will be administered intravenously (IV) on Day 1 and Day 15 of each cycle; cycle length is 28 days. Cohorts will be enrolled sequentially and will initially follow a 3+3 design.

Biological: Dostarlimab

Part 2A: Participants receiving dostarlimab

EXPERIMENTAL

In Part 2A, participants will receive fixed dose of 500 mg administered Q3W or 1000 mg administered Q6W dose on Day 1 of each cycle. Cycle duration for Q3W dosing is 21 days and Q6W dosing is 42 days. Cohorts will enroll participants with advanced solid tumor using a modified 6+6 design and will follow a 6+6 design.

Biological: Dostarlimab

Part 2B: Cohort A1 dMMR/MSI-H endometrial cancer

EXPERIMENTAL

Part 2B: Cohort A1 will include participants with mismatch repair deficient microsatellite instability high (dMMR/MSI-H) endometrial cancer who have progressed on or after platinum doublet therapy. These participants will receive dostarlimab 500 mg for Q3W for the first 4 cycles followed by 1000 mg Q6W for all subsequent cycles. Participants have received no more than 2 lines of anti-cancer therapy for recurrent or advanced (Stage \>= IIIB) disease.

Biological: Dostarlimab

Part 2B: Cohort A2 MMR-proficient/MSS endometrial cancer

EXPERIMENTAL

Part 2B: Cohort A2 will include participants with MMR-proficient/MSS endometrial cancer who have progressed on or after platinum doublet therapy. These participants will receive dostarlimab 500 mg for Q3W for the first 4 cycles followed by 1000 mg Q6W for all subsequent cycles. Participants have received no more than 2 lines of anti-cancer therapy for recurrent or advanced (Stage \>=IIIB) disease.

Biological: Dostarlimab

Part 2B: Cohort E NSCLC

EXPERIMENTAL

Part 2B: Cohort E NSCLC will include participants with non-small cell lung cancer (NSCLC) who progressed after at least 1 prior platinum-based systemic chemotherapy regimen for recurrent or advanced disease. These participants will receive dostarlimab 500 mg for Q3W for the first 4 cycles followed by 1000 mg Q6W for all subsequent cycles.

Biological: Dostarlimab

Part 2B: Cohort F non-endometrial dMMR/MSI-H or POLE-Mut cancers

EXPERIMENTAL

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. These participants will receive dostarlimab 500 mg for Q3W for the first 4 cycles followed by 1000 mg Q6W for all subsequent cycles.

Biological: Dostarlimab

Part 2B: Cohort G PROC without known BRCA

EXPERIMENTAL

Participants with advanced, relapsed, high-grade serous, endometrioid, or clear cell ovarian, fallopian tube, or primary peritoneal cancer without known breast cancer susceptibility gene (BRCA) mutation who have platinum-resistant disease receiving dostarlimab and who have also been previously treated with bevacizumab. These participants will receive dostarlimab 500 mg for Q3W for the first 4 cycles followed by 1000 mg Q6W for all subsequent cycles.

Biological: Dostarlimab

Interventions

Dostarlimab BIOLOGICAL

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.

Part 1: Participants receiving dostarlimab; Part 2A: Participants receiving dostarlimab; Part 2B: Cohort A1 dMMR/MSI-H endometrial cancer; Part 2B: Cohort A2 MMR-proficient/MSS endometrial cancer; Part 2B: Cohort E NSCLC; Part 2B: Cohort F non-endometrial dMMR/MSI-H or POLE-Mut cancers; Part 2B: Cohort G PROC without known BRCA

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant is at least 18 years of age.
• Participant has proven recurrent or advanced solid tumor and has disease progression after treatment with available anticancer 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 or advanced solid tumor B. Part 2A: : Any histologically or cytologically proven recurrent or 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: 1) Cohort A1 (dMMR/MSI-H endometrial cancer) and 2) 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 anticancer therapy for recurrent or advanced (\>=Stage IIIB) disease. Prior treatment with hormone therapies is acceptable and does not count towards the number of anticancer 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 anticancer 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) 4) 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.

You may not qualify if:

• 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 CNS metastasis 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 documented presence of hepatitis B surface antigen \[HBsAg\] at screening or within 3 months prior to the first dose of study intervention. Participants with a negative HbsAg and positive hepatitis B virus core antibody (HBcAb) result are eligible only if HBV DNA is negative.
• 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 anticancer therapy (chemotherapy, targeted therapies, radiotherapy, or immunotherapy) within 21 days prior to study Day 1
• 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.

Sponsors & Collaborators

• Tesaro, Inc.: lead

Study Sites (105)

GSK Investigational Site

Birmingham, Alabama, 35233, United States

Location

GSK Investigational Site

Goodyear, Arizona, 85338, United States

Location

GSK Investigational Site

Scottsdale, Arizona, 85258, United States

Location

GSK Investigational Site

Fayetteville, Arkansas, 72703, United States

Location

GSK Investigational Site

Encinitas, California, 92024, United States

Location

GSK Investigational Site

La Jolla, California, 92093, United States

Location

GSK Investigational Site

Los Angeles, California, 90095, United States

Location

GSK Investigational Site

Newport Beach, California, 92663, United States

Location

GSK Investigational Site

San Francisco, California, 94115, United States

Location

GSK Investigational Site

San Marcos, California, 92069, United States

Location

GSK Investigational Site

Santa Monica, California, 90403, United States

Location

GSK Investigational Site

Washington D.C., District of Columbia, 20007, United States

Location

GSK Investigational Site

Miami, Florida, 33136, United States

Location

GSK Investigational Site

Tampa, Florida, 33612, United States

Location

GSK Investigational Site

Augusta, Georgia, 30912, United States

Location

GSK Investigational Site

Chicago, Illinois, 60637, United States

Location

GSK Investigational Site

Fairway, Kansas, 66205, United States

Location

GSK Investigational Site

Scarborough, Maine, 04074, United States

Location

GSK Investigational Site

Baltimore, Maryland, 21231, United States

Location

GSK Investigational Site

Boston, Massachusetts, 02114, United States

Location

GSK Investigational Site

Boston, Massachusetts, 02215, United States

Location

GSK Investigational Site

Detroit, Michigan, 48201, United States

Location

GSK Investigational Site

Kansas City, Missouri, 64111, United States

Location

GSK Investigational Site

Farmington, New Mexico, 87401, United States

Location

GSK Investigational Site

Albany, New York, 12208, United States

Location

GSK Investigational Site

Brooklyn, New York, 11203, United States

Location

GSK Investigational Site

Jamaica, New York, 11432, United States

Location

GSK Investigational Site

New York, New York, 10016, United States

Location

GSK Investigational Site

Charlotte, North Carolina, 28204, United States

Location

GSK Investigational Site

Cleveland, Ohio, 44106, United States

Location

GSK Investigational Site

Columbus, Ohio, 43210, United States

Location

GSK Investigational Site

Hilliard, Ohio, 43026, United States

Location

GSK Investigational Site

Hilliard, Ohio, 43210, United States

Location

GSK Investigational Site

Oklahoma City, Oklahoma, 73104, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19104, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19111, United States

Location

GSK Investigational Site

Providence, Rhode Island, 02905, United States

Location

GSK Investigational Site

Dallas, Texas, 75230, United States

Location

GSK Investigational Site

Dallas, Texas, 75290-9032, United States

Location

GSK Investigational Site

San Antonio, Texas, 78229, United States

Location

GSK Investigational Site

Salt Lake City, Utah, 84112, United States

Location

GSK Investigational Site

Charlottesville, Virginia, 22903, United States

Location

GSK Investigational Site

Seattle, Washington, 98104, United States

Location

GSK Investigational Site

Seattle, Washington, 98195, United States

Location

GSK Investigational Site

Spokane, Washington, 99202, United States

Location

GSK Investigational Site

Spokane, Washington, 99204, United States

Location

GSK Investigational Site

Milwaukee, Wisconsin, 53226, United States

Location

GSK Investigational Site

São Paulo, 01246-000, Brazil

Location

GSK Investigational Site

Calgary, Alberta, T2N 4N2, Canada

Location

GSK Investigational Site

Edmonton, Alberta, T6G 1Z2, Canada

Location

GSK Investigational Site

Kelowna, British Columbia, V1Y 5L3, Canada

Location

GSK Investigational Site

Vancouver, British Columbia, V5Z 4E6, Canada

Location

GSK Investigational Site

Hamilton, Ontario, L8V 5C2, Canada

Location

GSK Investigational Site

London, Ontario, N6A 4L6, Canada

Location

GSK Investigational Site

Toronto, Ontario, M5G 2M9, Canada

Location

GSK Investigational Site

Montreal, Quebec, H2L 4M1, Canada

Location

GSK Investigational Site

Montreal, Quebec, H4A 3J1, Canada

Location

GSK Investigational Site

Hořovice, 26831, Czechia

Location

GSK Investigational Site

Zlín, 762 75, Czechia

Location

GSK Investigational Site

Copenhagen, DK- 2100, Denmark

Location

GSK Investigational Site

Odense C, 5000, Denmark

Location

GSK Investigational Site

Caen, 14076, France

Location

GSK Investigational Site

Lille, 59000, France

Location

GSK Investigational Site

Marseille, 13273, France

Location

GSK Investigational Site

Paris, 75571, France

Location

GSK Investigational Site

Paris, 75908, France

Location

GSK Investigational Site

Saint-Herblain, 44805, France

Location

GSK Investigational Site

Villejuif, 94805, France

Location

GSK Investigational Site

Milan, 20132, Italy

Location

GSK Investigational Site

Milan, 20133, Italy

Location

GSK Investigational Site

Milan, 20141, Italy

Location

GSK Investigational Site

Modena, 41100, Italy

Location

GSK Investigational Site

Naples, 80131, Italy

Location

GSK Investigational Site

Roma, 00144, Italy

Location

GSK Investigational Site

Verona, 37134, Italy

Location

GSK Investigational Site

Gdynia, 81-519, Poland

Location

GSK Investigational Site

Lublin, 20-090, Poland

Location

GSK Investigational Site

Olsztyn, 10-513, Poland

Location

GSK Investigational Site

Olsztyn, 10-561, Poland

Location

GSK Investigational Site

Torun, 87-100, Poland

Location

GSK Investigational Site

Barcelona, 08036, Spain

Location

GSK Investigational Site

Barcelona, 08907, Spain

Location

GSK Investigational Site

Barcelona, 8035, Spain

Location

GSK Investigational Site

Girona, 08907, Spain

Location

GSK Investigational Site

Girona, 17007, Spain

Location

GSK Investigational Site

Madrid, 28027, Spain

Location

GSK Investigational Site

Madrid, 28040, Spain

Location

GSK Investigational Site

Madrid, 28046, Spain

Location

GSK Investigational Site

Madrid, 28050, Spain

Location

GSK Investigational Site

Málaga, 29010, Spain

Location

GSK Investigational Site

Pamplona, 31008, Spain

Location

GSK Investigational Site

Santiago de Compostela, 15706, Spain

Location

GSK Investigational Site

Seville, 41013, Spain

Location

GSK Investigational Site

Valencia, 46009, Spain

Location

GSK Investigational Site

Valencia, 46010, Spain

Location

GSK Investigational Site

Zaragoza, 50009, Spain

Location

GSK Investigational Site

Aberdeen, AB25 2ZN, United Kingdom

Location

GSK Investigational Site

London, SE1 9RT, United Kingdom

Location

GSK Investigational Site

London, SW3 6JJ, United Kingdom

Location

GSK Investigational Site

London, W1G 6AD, United Kingdom

Location

GSK Investigational Site

London, W1T 7HA, United Kingdom

Location

GSK Investigational Site

Manchester, M20 4BX, United Kingdom

Location

GSK Investigational Site

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

GSK Investigational Site

Oxford, OX3 7LE, United Kingdom

Location

GSK Investigational Site

Sutton, SW36JJ, United Kingdom

Location

Related Publications (13)

• 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.

  PMID: 34750637 BACKGROUND

• 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

  BACKGROUND

• 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

  BACKGROUND

• 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.

  PMID: 34313545 BACKGROUND

• 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.

  PMID: 35064011 BACKGROUND

• 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 Oct 3;32(10):1250-1257. doi: 10.1136/ijgc-2022-003492.

  PMID: 35973737 BACKGROUND

• 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.

  PMID: 36823349 BACKGROUND

• Andre T, Berton D, Curigliano G, Sabatier R, Tinker AV, Oaknin A, Ellard S, de Braud F, Arkenau HT, Trigo J, Gravina A, Kristeleit R, Moreno V, Abdeddaim C, Vano YA, Samouelian V, Miller R, Boni V, Torres AA, Gilbert L, Brown J, Dewal N, Dabrowski C, Antony G, Zografos E, Veneris J, Banerjee S. Antitumor Activity and Safety of Dostarlimab Monotherapy in Patients With Mismatch Repair Deficient Solid Tumors: A Nonrandomized Controlled Trial. JAMA Netw Open. 2023 Nov 1;6(11):e2341165. doi: 10.1001/jamanetworkopen.2023.41165.

  PMID: 37917058 DERIVED

• Rodrigues M, Eberst L, Follana P, Gauthier L, Jacquemin V, Tessier C, El Mouaddin N, Boudier P, Fiteni F, Angeli E, Roche S, Delanoy N, Sabatier R, Flippot R, de la Motte Rouge T. Real-world dostarlimab use in advanced/recurrent endometrial cancer in France. Bull Cancer. 2023 Oct;110(10):1041-1050. doi: 10.1016/j.bulcan.2023.06.009. Epub 2023 Aug 31.

  PMID: 37659907 DERIVED

• Oaknin A, Pothuri B, Gilbert L, Sabatier R, Brown J, Ghamande S, Mathews C, O'Malley DM, Kristeleit R, Boni V, Gravina A, Banerjee S, Miller R, Pikiel J, Mirza MR, Dewal N, Antony G, Dong Y, Zografos E, Veneris J, Tinker AV. Safety, Efficacy, and Biomarker Analyses of Dostarlimab in Patients with Endometrial Cancer: Interim Results of the Phase I GARNET Study. Clin Cancer Res. 2023 Nov 14;29(22):4564-4574. doi: 10.1158/1078-0432.CCR-22-3915.

  PMID: 37363992 DERIVED

• Moreno V, Roda D, Pikiel J, Trigo J, Bosch-Barrera J, Drew Y, Kristeleit R, Hiret S, Bajor DL, Cruz P, Beck JT, Ghosh S, Dabrowski C, Antony G, Duan T, Veneris J, Zografos E, Subramanian J. Safety and Efficacy of Dostarlimab in Patients With Recurrent/Advanced Non-small Cell Lung Cancer: Results from Cohort E of the Phase I GARNET Trial. Clin Lung Cancer. 2022 Nov;23(7):e415-e427. doi: 10.1016/j.cllc.2022.05.013. Epub 2022 May 23.

  PMID: 35729005 DERIVED

• Oaknin A, Tinker AV, Gilbert L, Samouelian V, Mathews C, Brown J, Barretina-Ginesta MP, Moreno V, Gravina A, Abdeddaim C, Banerjee S, Guo W, Danaee H, Im E, Sabatier R. Clinical activity and safety of the anti-PD-1 monoclonal antibody dostarlimab for patients with recurrent or advanced dMMR endometrial cancer. Future Oncol. 2021 Oct 1;17(29):3781-3785. doi: 10.2217/fon-2021-0598. Epub 2021 Aug 24.

  PMID: 34427115 DERIVED

• Oaknin A, Tinker AV, Gilbert L, Samouelian V, Mathews C, Brown J, Barretina-Ginesta MP, Moreno V, Gravina A, Abdeddaim C, Banerjee S, Guo W, Danaee H, Im E, Sabatier R. Clinical Activity and Safety of the Anti-Programmed Death 1 Monoclonal Antibody Dostarlimab for Patients With Recurrent or Advanced Mismatch Repair-Deficient Endometrial Cancer: A Nonrandomized Phase 1 Clinical Trial. JAMA Oncol. 2020 Nov 1;6(11):1766-1772. doi: 10.1001/jamaoncol.2020.4515.

  PMID: 33001143 DERIVED

MeSH Terms

Conditions

Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

dostarlimab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2016
• First Posted: March 22, 2016
• Study Start: March 7, 2016
• Primary Completion (Estimated): May 18, 2026
• Study Completion (Estimated): January 25, 2027
• Last Updated: January 13, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

CA (9); US (47); BR (1); GB (9); IT (7); PL (5); ES (16); FR (7); CZ (2); DK (2)