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Dostarlimab

Phase 3

Neoplasms | Monoclonal antibody | Oncology |GSK plc|Last Updated: Jul 21, 2026

Success Probability
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Trial Design
RandomizedDouble-BlindCONTROLLEDDMC
Total Trials3
Total Enrollment1,577
FDA Designations
No designations recorded
Clinical trial landscape

Dostarlimab · 16 trials · 24 indications

Phase 3 4Phase 2 10Phase 1 2
NCT06472076A Study of Belrestotug Plus Dostarlimab Compared With Placebo Plus Pembrolizumab in Previously Untreated Participants With Programmed Death Ligand 1 (PD-L1) High Non-small-cell Lung Cancer (NSCLC)Lung Cancer, Non-Small Cell
ACTIVE NOT_RECRUITING88 Analytics
NCT06256588A Study of Dostarlimab vs Placebo After Chemoradiation in Adult Participants With Locally Advanced Unresected Head and Neck Squamous Cell CarcinomaNeoplasms, Head and Neck
RECRUITING864 Analytics
NCT05855200Study of Perioperative Dostarlimab in Participants With Untreated T4N0 or Stage III dMMR/MSI-H Resectable Colon CancerColonic Neoplasms
RECRUITING892 Analytics
NCT03981796A Study to Evaluate Dostarlimab Plus Carboplatin-paclitaxel Versus Placebo Plus Carboplatin-paclitaxel in Participants With Recurrent or Primary Advanced Endometrial CancerNeoplasms
ACTIVE NOT_RECRUITING785 Analytics
PHASE3ACTIVE NOT_RECRUITING
A Study of Belrestotug Plus Dostarlimab Compared With Placebo Plus Pembrolizumab in Previously Untreated Participants With Programmed Death Ligand 1 (PD-L1) High Non-small-cell Lung Cancer (NSCLC)
Lung Cancer, Non-Small CellUnlock trial analytics
PHASE3RECRUITING
A Study of Dostarlimab vs Placebo After Chemoradiation in Adult Participants With Locally Advanced Unresected Head and Neck Squamous Cell Carcinoma
Neoplasms, Head and NeckUnlock trial analytics
PHASE3RECRUITING
Study of Perioperative Dostarlimab in Participants With Untreated T4N0 or Stage III dMMR/MSI-H Resectable Colon Cancer
Colonic NeoplasmsUnlock trial analytics
PHASE3ACTIVE NOT_RECRUITING
A Study to Evaluate Dostarlimab Plus Carboplatin-paclitaxel Versus Placebo Plus Carboplatin-paclitaxel in Participants With Recurrent or Primary Advanced Endometrial Cancer
NeoplasmsUnlock trial analytics
Study Endpoints
Primary Endpoints
Number of Participants with Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Up to approximately 138 weeks
Number of Participants with TEAEs or SAEs leading to dose withdrawals or treatment discontinuation
Up to approximately 138 weeks
Event-free Survival (EFS) Assessed by Blinded Independent Central Review (BICR)
Up to approximately 5 years

Event Free Survival (EFS) is defined as the time from the date of randomization to the date of an event, where an event is defined as locoregional progression or recurrence, or distant metastasis per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as per BICR; Salvage surgery at the primary tumor site; Neck dissection or surgery performed \>20 weeks after completion of Concomitant Chemoradiotherapy (CRT) when invasive cancer is present or Death from any cause.

Parts 1 and 2: Progression-Free Survival (PFS) - investigator assessment
Up to 6 years
Part 1: Overall survival
Up to 6 years
Durable Response Rate for 12 months (DRR12) assessed by Blinded Independent Central Review (BICR)
Up to approximately 148 weeks

DRR12 is defined as the proportion of participants with confirmed Complete Response (CR) or Partial Response (PR), and Duration of Response (DOR) lasting greater than or equal to (≥) 12 months, per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1).

Major pathological response (mPR) rate
Up to approximately 18 weeks

mPR rate is defined as the proportion of participants with ≤10% residual viable tumor (RVT) value in the surgical resection sample as determined by local assessment.

Number of participants with adverse events (AEs), serious adverse events (SAEs), immune-mediated adverse events (imAEs), and AEs leading to death or discontinuation of study intervention
Up to approximately 105 weeks
Number of Participants with Sustained Complete Clinical Response for 12 Months (cCR12) as assessed by Independent Central Review (ICR)
18 months

cCR12 is achieved when a participant maintains complete clinical response (cCR) as assessed by Independent central review (ICR) for 12 months from the first disease assessment after last dose of study intervention. Timeframe calculation includes 6 months (9 cycles of dostarlimab, with each cycle lasting 21 days) plus an additional 12 months of assessment time, amounting to a total of 18 months.

Progression-free survival
From randomization until disease progression or death from any cause, up to 3 years.

The progression-free survival is the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse.

Progression Free Survival
Up to approximately 48 months

The time from the date of randomization until first documentation of disease progression, as determined by investigator assessment based on RECIST 1.1, or death due to any cause, whichever occurs first.

Confirmed Objective Response Rate (ORR) compared between Sub studies and Dostarlimab monotherapy
Up to approximately 24 months

Confirmed ORR is defined as the percentage of participants achieving confirmed Complete Response (CR) or Partial Response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator assessment.

Part 1: Number of Participants With Any Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) (Arm 4)
Up to approximately 97 weeks

An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose resulted in death, is life threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/ incapacity, is a congenital anomaly/ birth defect, other situations and is associated with liver injury or impaired liver function. SAEs are subset of AEs. A TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA) coding system.

Part 1: Number of Participants With Any TEAEs and SAEs (Arm 5)
Up to approximately 107 weeks

An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose resulted in death, is life threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/ incapacity, is a congenital anomaly/ birth defect, other situations and is associated with liver injury or impaired liver function. SAEs are subset of AEs. A TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA) coding system.

Part 1: Number of Participants With Dose Limiting Toxicity (DLT) (Arm 4 and Arm 5)
Up to 21 days

A DLT is an AE meeting criteria such as, hematologic toxicities of Grade (G) 4 neutropenia/anemia/thrombocytopenia (G3 if bleeding). Non-hematological toxicities include persistent G2 eye events, colitis/diarrhea (G2 unresolved to ≤ G1 within 7 days despite immunosuppressive therapy, G3 for ≥ 72 hours, any G4), G3 pneumonitis, rash (unresolved to ≤ G2 within 2 weeks despite treatment), hypersensitivity/IRR, liver events meeting Hy's Law criteria. G3 toxicity unresolved to ≤G1 or baseline within 3 days with supportive care, or any G4 toxicity. Exclusions include G3 events of electrolyte imbalances correctable within 72 hours without effects, nausea/vomiting/fatigue resolving within 7 days, lymphopenia, and enzyme elevations without pancreatitis. Considerations for DLTs include permanent treatment discontinuation, investigator/sponsor judgment-based events including post-observation period toxicities.

Part 1: Number of Participants Requiring Dose Modifications (Arm 4)
Up to approximately 97 weeks

Number of participants with dose modifications (missed doses, dose delays and infusion interruptions) is summarized.

Part 1: Number of Participants Requiring Dose Modifications (Arm 5)
Up to approximately 107 weeks

Number of participants with dose modifications (missed doses, dose delays and infusion interruptions) is summarized.

Part 1: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (Arm 4)
Up to approximately 97 weeks

Performance Status was assessed using the ECOG scale (Grades 0-5), where 0: Fully active, able to carry on all pre-disease performance without restriction. Grade 1: Restricted in physically strenuous activity but ambulatory \& able to carry out work of light or sedentary nature; Grade 2 - Ambulatory \& capable of all self-care but unable to carry out any work activities. Up and about more than (\>) 50% of waking hours; Grade 3 -Capable of only limited self-care, confined to bed or chair \> 50% of waking hours; Grade 4 -Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair; Grade 5 -Dead.

Part 1: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (Arm 5)
Up to approximately 107 weeks

Performance Status was assessed using the ECOG scale (Grades 0-5), where 0: Fully active, able to carry on all pre-disease performance without restriction. Grade 1: Restricted in physically strenuous activity but ambulatory \& able to carry out work of light or sedentary nature; Grade 2 - Ambulatory \& capable of all self-care but unable to carry out any work activities. Up and about more than (\>) 50% of waking hours; Grade 3 -Capable of only limited self-care, confined to bed or chair \> 50% of waking hours; Grade 4 -Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair; Grade 5 -Dead

Part 1: Number of Participants With Worst-case Post Baseline Increase From Baseline in Vital Signs (Arm 4)
Up to approximately 97 weeks

Vital signs including systolic blood pressure (SBP), diastolic BP (DBP), pulse rate (PR) and body temperature (BT) were measured for the participants. DBP: Grade 0 (\<80 millimeters of mercury \[mmHg\]), Grade 1 (80-89 mmHg), Grade 2 (90-99 mmHg), Grade 3 (\>=100 mmHg); SBP: Grade 0 (\<120 mmHg), Grade 1 (120-139 mmHg), Grade 2 (140-159 mmHg), Grade 3 (\>=160 mmHg); PR categories include: 'Decrease to \< 60 beats per minutes \[bpm\]', 'Change to Normal' or 'No Change', and 'Increase to \>100 bpm'; BT categories include 'Decrease to \<=35 degrees Celsius °C', 'Change to Normal' or 'No Change', and 'Increase to \>=38 °C'. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Worst Case Post-Baseline includes all scheduled and unscheduled visits post baseline.

Part 1: Number of Participants With Worst-case Post Baseline Increase From Baseline in Vital Signs (Arm 5)
Up to approximately 107 weeks

Vital signs including systolic blood pressure (SBP), diastolic BP (DBP), pulse rate (PR) and body temperature (BT) were measured for the participants. DBP: Grade 0 (\<80 millimeters of mercury \[mmHg\]), Grade 1 (80-89 mmHg), Grade 2 (90-99 mmHg), Grade 3 (\>=100 mmHg); SBP: Grade 0 (\<120 mmHg), Grade 1 (120-139 mmHg), Grade 2 (140-159 mmHg), Grade 3 (\>=160 mmHg); PR categories include: 'Decrease to \< 60 beats per minutes \[bpm\]', 'Change to Normal' or 'No Change', and 'Increase to \>100 bpm'; BT categories include 'Decrease to \<=35 degrees Celsius °C', 'Change to Normal' or 'No Change', and 'Increase to \>=38 °C'. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Worst Case Post-Baseline includes all scheduled and unscheduled visits post baseline.

Part 1: Number of Participants Who Received Concomitant Medications (Arm 4)
Up to approximately 97 weeks

Number of participants who received Concomitant medications is summarized.

Part 1: Number of Participants Who Received Concomitant Medications (Arm 5)
Up to approximately 107 weeks

Number of participants who received Concomitant medications is summarized.

Part 1: Number of Participants With Worst-case Post Baseline Relative to Baseline Electrocardiogram (ECG) Findings (Arm 4)
Up to approximately 97 weeks

Number of participants with worst-case post baseline (WCPB) from baseline ECG findings is summarized as clinically significant. Data is summarized as Normal, Abnormal - Not Clinically Significant (NCS) and Abnormal - Clinically Significant (CS). Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Worst Case Post-Baseline includes all scheduled and unscheduled visits post baseline.

Part 1: Number of Participants With Worst-case Post Baseline Relative to Baseline ECG Findings (Arm 5)
Up to approximately 107 weeks

Number of participants with worst-case post baseline (WCPB) from baseline ECG findings is summarized as clinically significant. Data is summarized as Normal, Abnormal - Not Clinically Significant (NCS) and Abnormal - Clinically Significant (CS). Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Worst Case Post-Baseline includes all scheduled and unscheduled visits post baseline.

Part 1: Number of Participants With Worst-case Post Baseline Relative to Baseline in QTcF Interval (Arm 4)
Up to approximately 97 weeks

The QTcF values based on Fridericia formula were rounded to the integer and the values are categorized into the following ranges, inclusively: Grade 0 (\<450 millisecond (msec)), Grade 1 (≥450-≤480 msec), Grade 2 (≥481-≤500 msec), and Grade 3 (≥501 msec). Missing baseline grades were assumed to be Grade 0. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Worst Case Post-Baseline includes all scheduled and unscheduled visits post baseline.

Part 1: Number of Participants With Worst-case Post Baseline Relative to Baseline in QTcF Interval (Arm 5)
Up to approximately 107 weeks

The QTcF values based on Fridericia formula were rounded to the integer and the values are categorized into the following ranges, inclusively: Grade 0 (\<450 millisecond (msec)), Grade 1 (≥450-≤480 msec), Grade 2 (≥481-≤500 msec), and Grade 3 (≥501 msec). Missing baseline grades were assumed to be Grade 0. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Worst Case Post-Baseline includes all scheduled and unscheduled visits post baseline.

Part 1: Number of Participants With Worst-case Post Baseline Relative to Baseline in Left Ventricular Ejection Fraction (LVEF) (Arm 4)
Up to approximately 97 weeks

Number of participants with worst case post-baseline in LVEF from baseline is summarized as 'any decrease (\>0%-\<10% Decrease, 10%-19% Decrease, \>=20% Decrease)', '\>=10% Decrease and \>= Lower limit of normal (LLN)', '\>=10% Decrease and \< LLN', '\>=20% Decrease and \>= LLN' and '\>=20% Decrease and \< LLN' . An increase is defined as an increase in grade relative to Baseline grade. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Worst Case Post-Baseline includes all scheduled and unscheduled visits post baseline.

Part 1: Number of Participants With Worst-case Post Baseline Relative to Baseline in Left Ventricular Ejection Fraction (LVEF) (Arm 5)
Up to approximately 107 weeks

Number of participants with worst case post-baseline in LVEF from baseline is summarized as 'any decrease (\>0%-\<10% Decrease, 10%-19% Decrease, \>=20% Decrease)', '\>=10% Decrease and \>= Lower limit of normal (LLN)', '\>=10% Decrease and \< LLN', '\>=20% Decrease and \>= LLN' and '\>=20% Decrease and \< LLN' . An increase is defined as an increase in grade relative to Baseline grade. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Worst Case Post-Baseline includes all scheduled and unscheduled visits post baseline.

Part 1: Number of Participants With Worst Case Hematology Results by Maximum Grade Increase Post-Baseline Relative to Baseline (Arm 4)
Up to approximately 97 weeks

Blood samples were collected for the analysis of hematology parameters and are categorized in alignment with Common Terminology Criteria for Adverse Events (CTCAE) version 5 as Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; and Grade 4: life-threatening consequences. Higher grade indicates greater severity. An increase in grade is defined relative to the Baseline grade. Participants with missing baseline values are assumed to have baseline value of grade 0. Any worst-case post baseline increase in grade along with any increase to a maximum grade of 3 and 4 is summarized. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Worst Case Post-Baseline includes all scheduled and unscheduled visits post baseline.

Part 1: Number of Participants With Worst Case Hematology Results by Maximum Grade Increase Post-Baseline Relative to Baseline (Arm 5)
Up to approximately 107 weeks

Blood samples were collected for the analysis of hematology parameters and are categorized in alignment with Common Terminology Criteria for Adverse Events (CTCAE) version 5 as Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; and Grade 4: life-threatening consequences. Higher grade indicates greater severity. An increase in grade is defined relative to the Baseline grade. Participants with missing baseline values are assumed to have baseline value of grade 0. Any worst-case post baseline increase in grade along with any increase to a maximum grade of 3 and 4 is summarized. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Worst Case Post-Baseline includes all scheduled and unscheduled visits post baseline.

Part 1: Number of Participants With Worst Case Clinical Chemistry Results by Maximum Grade Increase Post-Baseline Relative to Baseline (Arm 4)
Up to approximately 97 weeks

Blood samples were collected for the analysis of clinical chemistry parameters and are categorized in alignment with Common Terminology Criteria for Adverse Events (CTCAE) version 5 as Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; and Grade 4: life-threatening consequences. Higher grade indicates greater severity. An increase in grade is defined relative to the Baseline grade. Participants with missing baseline values are assumed to have baseline value of grade 0. Any worst-case post baseline increase in grade along with any increase to a maximum grade of 3 and 4 is summarized. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Worst Case Post-Baseline includes all scheduled and unscheduled visits post baseline.

Part 1: Number of Participants With Worst Case Clinical Chemistry Results by Maximum Grade Increase Post-Baseline Relative to Baseline (Arm 5)
Up to approximately 107 weeks

Blood samples were collected for the analysis of clinical chemistry parameters and are categorized in alignment with Common Terminology Criteria for Adverse Events (CTCAE) version 5 as Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; and Grade 4: life-threatening consequences. Higher grade indicates greater severity. An increase in grade is defined relative to the Baseline grade. Participants with missing baseline values are assumed to have baseline value of grade 0. Any worst-case post baseline increase in grade along with any increase to a maximum grade of 3 and 4 is summarized. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Worst Case Post-Baseline includes all scheduled and unscheduled visits post baseline.

Part 1: Number of Participants With Worst Case Change Post-baseline in Clinical Chemistry Parameters (Arm 4)
Up to approximately 97 weeks

Blood samples were collected for analysis of clinical chemistry. The summaries of worst-case post baseline (WCPB) from baseline (B) with respect to normal range was analyzed. Data is presented as "XXX B YYY, WCPB YYY", where XXX denotes lab parameter and YYY is high/normal/low. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Worst Case Post-Baseline includes all scheduled and unscheduled visits post baseline.

Part 1: Number of Participants With Worst Case Change Post-baseline in Clinical Chemistry Parameters (Arm 5)
Up to approximately 107 weeks

Blood samples were collected for analysis of clinical chemistry. The summaries of worst-case post baseline (WCPB) from baseline (B) with respect to normal range was analyzed. Data is presented as "XXX B YYY, WCPB YYY", where XXX denotes lab parameter and YYY is high/normal/low. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Worst Case Post-Baseline includes all scheduled and unscheduled visits post baseline.

Part 1: Number of Participants With Worst-Case Urinalysis Results Post-Baseline Relative to Baseline (Arm 4)
Up to approximately 97 weeks

Urinalysis was performed. Participants with missing value at baseline are assumed to be negative at baseline. All increases are from baseline. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

Part 1: Number of Participants With Worst-Case Urinalysis Results Post-Baseline Relative to Baseline (Arm 5)
Up to approximately 107 weeks

Urinalysis was performed. Participants with missing value at baseline are assumed to be negative at baseline. All increases are from baseline. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

Part 2: Overall Survival (OS)
Up to approximately 107 weeks

OS is defined as the time from date of randomization to the date of death, irrespective of the cause of death.

Confirmed Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment
Up to approximately 38 Months

ORR was defined as percentage of participants with a confirmed investigator-assessed Best Overall Response (BOR) of confirmed complete response (CR) or partial response (PR), evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. CR is defined as the disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 millimeters (mm).

1-year disease free survival
1 year after the start of the study treatment

Disease-free survival (DFS) is defined as the time from the date of study treatment initiation to the date of first record of any of the following events: Investigator determined: Locoregional progression or recurrence. Distant metastasis. Neck dissection or surgery performed for clinical or radiological disease progression (RECIST 1.1) \> 20 weeks from the end of radiation therapy with tumor present on final pathology. Death due to any cause. Patients not presenting any of the previous events will be censored at the date of last assessment.

Part 1: Number of participants with treatment emergent AEs (TEAEs)
Up to 2 years

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.

Part 1: Number of participants with immune mediated AEs of interest
Up to 2 years

Participants with immune related AEs of interest will be assessed.

Part 1: Number of participants with abnormal hematology parameters
Up to 2 years

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).

Part 1: Number of participants with abnormal clinical chemistry parameters
Up to 2 years

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.

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

Number of participants will be assessed.

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

Number of participants will be assessed.

Part 1: Number of participants with abnormal electrocardiogram (ECG) parameters
Up to 2 years

Participants will be supine or in a semi-recumbent position and rested for approximately 2 minutes before ECGs are recorded.

Part 1: Number of participants receiving concomitant medications
Up to 2 years

Concomitant medications will be recorded.

Part 2A: Number of participants with TEAEs
Up to 2 years

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.

Part 2A: Number of participants with immune mediated AEs of interest
Up to 2 years

Participants with immune related AEs of interest will be assessed.

Part 2A: Number of participants with abnormal hematology parameters
Up to 2 years

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.

Part 2A: Number of participants with abnormal clinical chemistry parameters
Up to 2 years

Blood samples will be collected to assess the following chemistry parameters: sodium, potassium, calcium, magnesium, creatinine, bilirubin, AST, ALT, and albumin.

Part 2A: Number of participants with abnormal ECG
Up to 2 years

Participants will be supine or in a semi-recumbent position and rested for approximately 2 minutes before ECGs are recorded.

Part 2A: Number of participants receiving concomitant medications
Up to 2 years

Concomitant medications will be recorded.

Part 2B: Number of participants with TEAEs
Up to 2 years

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.

Part 2B: Number of participants with immune related AEs of interest
Up to 2 years

Participants with immune related AEs of interest will be assessed.

Part 2B: Number of participants with abnormal hematology parameters
Up to 2 years

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.

Part 2B: Number of participants with abnormal clinical chemistry parameters
Up to 2 years

Blood samples will be collected to assess the following chemistry parameters: sodium, potassium, calcium, magnesium, creatinine, bilirubin, AST, ALT, and albumin.

Part 2B: Number of participants with abnormal ECG parameters
Up to 2 years

Participants will be supine or in a semi-recumbent position and rested for approximately 2 minutes before ECGs are recorded.

Part 2B: Number of participants receiving concomitant medications
Up to 2 years

Concomitant medications will be recorded.

Part 2B: Cohort A1 Overall Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Up to 2 years

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.

Part 2B: Cohort F ORR by RECIST version 1.1
Up to 2 years

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

Part 2B: Cohort A2 ORR by RECIST version 1.1
Up to 2 years

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

Part 2B: Cohort G ORR by RECIST version 1.1
Up to 2 years

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

Part 2B: Cohort E ORR by immune related Response Evaluation Criteria in Solid Tumors per irRECIST
Up to 2 years

ORR is defined as the proportion of participants achieving CR or PR as assessed by investigator per irRECIST will be evaluated.

Part 2B: Cohort A1 Duration of response (DOR)
Up to 2 years

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.

Part 2B: Cohort F Duration of response (DOR)
Up to 2 years

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.

Part 2B: Cohort A2 Duration of response (DOR)
Up to 2 years

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.

Secondary Endpoints
Overall Survival (OS)
Up to approximately 5 years
Event-free Survival (EFS) assessed by investigator
Up to approximately 5 years
Number of Participants with treatment emergent adverse events (TEAEs), Immune-mediated TEAEs, and serious adverse events (SAEs) by severity
Up to approximately 5 years
Unlock Study Endpoints
Study Design & Arms
AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Dostarlimab plus belrestotugEXPERIMENTAL -
Pembrolizumab plus placeboACTIVE_COMPARATOR -
Arm A: DostarlimabEXPERIMENTAL -
Arm B: PlaceboPLACEBO_COMPARATOR -
DostarlimabEXPERIMENTALParticipants will receive Dostarlimab pre and post surgery
Standard of Care (SOC)ACTIVE_COMPARATORParticipants will receive SOC (FOLFOX/CAPEOX) or undergo expectant observation post surgery.
Arm 1: Participants receiving dostarlimab + Carboplatin-paclitaxel followed by dostarlimabACTIVE_COMPARATOR -
Arm 2: Participants receiving placebo + carboplatin-paclitaxel followed by placeboPLACEBO_COMPARATOR -
Arm 3: Participants receiving dostarlimab + carboplatin-paclitaxel followed by dostarlimab+niraparibACTIVE_COMPARATOR -
Arm 4: Participants receiving placebo + carboplatin-paclitaxel followed by placeboPLACEBO_COMPARATOR -
Dostarlimab-Carboplatin-Paclitaxel followed by Dostarlimab MonotherapyEXPERIMENTAL -
Dostarlimab plus CAPEOXEXPERIMENTALParticipants will receive dostarlimab plus CAPEOX (chemotherapy).
CAPEOXACTIVE_COMPARATORParticipants will receive CAPEOX (chemotherapy).
Dostarlimab monotherapyEXPERIMENTALParticipants will receive dostarlimab as monotherapy.
Standard of careACTIVE_COMPARATORPatients will receive the standard of care chemotherapy
Dostarlimab- Carboplatin-Paclitaxel followed by Dostarlimab MonotherapyEXPERIMENTAL -
Group AEXPERIMENTALDostarlimab monotherapy
Group BEXPERIMENTALDostarlimab + Bevacizumab combination therapy
Group CACTIVE_COMPARATORGeneral chemotherapy (one of Pegylated liposomal doxorubicin, Doxorubicin, Paclitaxel, and Gemcitabine)
Sub study 1: Dostarlimab and BelrestotugEXPERIMENTAL -
Sub study 2: Dostarlimab and nelistotugEXPERIMENTAL -
Sub study 3: Dosarlimab and Belrestotug and nelistotugEXPERIMENTAL -
Sub study 4: Dostarlimab and remzistotugEXPERIMENTAL -
Dostarlimab plus Belrestotug plus NelistotugEXPERIMENTAL -
Cohort A (Dostarlimab + Bevacizumab + Niraparib)EXPERIMENTAL -
Cohort AEXPERIMENTALThree stages: Neoadjuvant: single dose of dostarlimab 500 mg intravenously on day -21 and niraparib 200 or 300 mg orally once daily starting on day -14 until 48 hours prior to the start of definitive radiotherapy (day 0). Concurrent: definitive radiotherapy (70 Gy in 35 fractions, 1 fraction per day from Monday to Friday) with concurrent Cisplatin at a dose of 100 mg/m2 intravenously on day 1 of week 1, week 4 and week 7. Maintenance: dostarlimab to be administered as a single infusion dose of 500 mg on day 1 every 21 days from week 11 to week 48. Niraparib will be given once daily at a dose of 200 or 300 mg in cycles of 21 days.
Cohort BEXPERIMENTALThree stages: Neoadjuvant: single dose of dostarlimab 500 mg intravenously on day -21 and niraparib 200 or 300 mg orally once daily starting on day -14 until the start of definitive radiotherapy (day 0). Concurrent: definitive radiotherapy (70 Gy in 35 fractions, 1 fraction per day from Monday to Friday). Niraparib is to be given once daily on a continous basis (200 to 300 mg), from w1 d1 until end of w10 in cycles of 21 days. Maintenance: dostarlimab to be administered as a single infusion dose of 500 mg on day 1 every 21 days from week 11 to week 48. Niraparib will be given once daily on a continous basis at a dose of 200 or 300 mg in cycles of 21 days.
Part 1: Participants receiving dostarlimabEXPERIMENTALPart 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.
Part 2A: Participants receiving dostarlimabEXPERIMENTALIn 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.
Part 2B: Cohort A1 dMMR/MSI-H endometrial cancerEXPERIMENTALPart 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.
Part 2B: Cohort A2 MMR-proficient/MSS endometrial cancerEXPERIMENTALPart 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.
Part 2B: Cohort E NSCLCEXPERIMENTALPart 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.
Part 2B: Cohort F non-endometrial dMMR/MSI-H or POLE-Mut cancersEXPERIMENTALParticipants 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.
Part 2B: Cohort G PROC without known BRCAEXPERIMENTALParticipants 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.
Interventions
NameTypeDescription
DostarlimabBIOLOGICALDostarlimab will be administered.
BelrestotugBIOLOGICALBelrestotug will be administered.
PembrolizumabBIOLOGICALPembrolizumab will be administered.
PlaceboDRUGPlacebo will be administered.
CAPEOXDRUGCAPEOX will be administered.
FOLFOXDRUGFOLFOX will be administered.
Placebo matching dostarlimabDRUGParticipants will be administered placebo matching dostarlimab
CarboplatinDRUGParticipants will be administered carboplatin
PaclitaxelDRUGParticipants will be administered paclitaxel
NiraparibDRUGParticipants will be administered niraparib
Placebo matching NiraparibDRUGParticipants will be administered placebo matching Niraparib
ChemotherapyDRUG* mFOLFOX6 or FOLFIRI or XELOX regimen * FOLFOX or XELOX or TFOX regimen * FOLFIRINOX or gemcitabine-nab-paclitaxel or gemcitabine monotherapy. * Cisplatin and gemcitabine cisplatin or CAPOX or mFOLFOX6. * Etoposide-cisplatin-doxorubicin or mitotane * Cisplatin and gemcitabine or carboplatin and paclitaxel * Etoposide-cisplatin or etoposide-carboplatin * Doxorubicin and ifosfamide or doxorubicin monotherapy or doxorubicin and trabectedin.
BevacizumabDRUGIntravenous (IV) infusion
DoxorubicinDRUGIntravenous (IV) infusion
GemcitabineDRUGIntravenous (IV) infusion
Pegylated liposomal doxorubicinDRUGIntravenous (IV) infusion
NelistotugDRUGNelistotug will be administered.
RemzistotugDRUGRemzistotug will be administered.
Belrestotug.DRUGBelrestotug will be administered
cisplatin plus radiotherapyDRUGIn the concurrent phase
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Eligibility Criteria
Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites108

Inclusion Criteria: * Has a histologically or cytologically confirmed diagnosis of locally advanced, unresectable NSCLC (not eligible for curative surgery and/or definitive radiotherapy with or without chemotherapy), or Metastatic NSCLC * Has not received prior systemic therapy for their locally ad...

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