Cell Phone To The Death And ThereAfter

Cell Phone To The Death And ThereAfter

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In the extrinsic pathway (left), apoptosis is triggered by binding of a ligand to a cell surface death receptor with subsequent formation of a cytoplasmic death-inducing signaling complex that activates an initiator caspase (e.g., caspase-8). The intrinsic pathway (right) of apoptosis is triggered by DNA damage or various cell stressors, especially those that result in permeabilization of the mitochondrial outer membrane, and leads to formation of the caspase-activating complex or apoptosome. The initiator caspase in the intrinsic pathway is usually caspase-9. In both the extrinsic and the intrinsic pathways, initiator caspases activate effector (executioner) caspases, resulting in cell death with the characteristic morphologic features of apoptosis (shown at bottom).

The virus causes hepatocellular death, typically by oncotic necrosis, but sometimes by apoptosis. Note coagulative necrosis (lower left) with lytic necrosis (center left) and individual cells with features of apoptosis (arrows). H&E stain.

Layout table for study information Study Type : Interventional (Clinical Trial) EstimatedEnrollment : 740 participants Allocation: Non-Randomized Intervention Model: Sequential Assignment Masking: None (Open Label) Primary Purpose: Treatment Official Title: A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-042, an Anti-PD-1 Monoclonal Antibody, in Patients With Advanced Solid Tumors Actual Study Start Date : March 7, 2016 Estimated Primary Completion Date : May 15, 2026 Estimated Study Completion Date : October 27, 2027 Resource links provided by the National Library of Medicine MedlinePlus related topics: End of Life Issues Drug Information available for: Dostarlimab U.S. FDA Resources Arms and Interventions Go to Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information Arm Intervention/treatment Experimental: Part 1: Participants receiving dostarlimabPart 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: DostarlimabDostarlimab (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. Experimental: Part 2A: Participants receiving dostarlimabIn 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: DostarlimabDostarlimab (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. Experimental: Part 2B: Cohort A1 dMMR/MSI-H endometrial cancerPart 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: DostarlimabDostarlimab (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. Experimental: Part 2B: Cohort A2 MMR-proficient/MSS endometrial cancerPart 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: DostarlimabDostarlimab (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. Experimental: Part 2B: Cohort E NSCLCPart 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: DostarlimabDostarlimab (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. Experimental: Part 2B:Cohort F non-endometrial dMMR/MSI-H & POLE-Mut cancersParticipants 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: DostarlimabDostarlimab (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. Experimental: Part 2B: Cohort G PROC without known BRCAParticipants 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: DostarlimabDostarlimab (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. Outcome Measures Go to Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information Primary Outcome Measures : Part 1: Number of participants with treatment emergent AEs (TEAEs) [ Time Frame: 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 related AEs of interest [ Time Frame: Up to 2 years ]Participants with immune related AEs of interest will be assessed. Part 1: Number of participants with abnormal hematology parameters [ Time Frame: 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 [ Time Frame: Up to 2 years ]Blood samples will be collected to assess the following chemistry parameters: sodium, potassium, calcium, magnesium, chloride, glucose, creatinine, urea or blood urea nitrogen (BUN), amylase, bilirubin, alkaline phosphatase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total protein, albumin, lactate dehydrogenase. Part 1: Number of participants with abnormal thyroid function [ Time Frame: Up to 2 years ]Blood samples will be collected to assess the levels of thyroid-stimulating hormone (TSH); triiodothyronine (T3), or free triiodothyronine (FT3) and free thyroxine (FT4). Part 1: Number of participants with abnormal urine parameters [ Time Frame: Up to 2 years ]Urine samples will be collected to evaluate specific gravity, leucocyte esterase, nitrite, blood, protein, glucose, and ketones. Part 1: Number of participants with abnormal vital signs [ Time Frame: Up to 2 years ]Blood pressure, pulse rate, respiratory rate and temperature will be assessed. Part 1: Number of participants with abnormal electrocardiogram (ECG) parameters [ Time Frame: 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 with abnormal physical examination. [ Time Frame: Up to 2 years ]Physical examinations including weight will be assessed. Part 1: Number of participants receiving concomitant medications [ Time Frame: Up to 2 years ]Concomitant medications will be recorded. Part 2A: Number of participants with TEAEs [ Time Frame: 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 related AEs of interest [ Time Frame: Up to 2 years ]Participants with immune related AEs of interest will be assessed. Part 2A: Number of participants with abnormal hematology parameters [ Time Frame: 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 [ Time Frame: Up to 2 years ]Blood samples will be collected to assess the following chemistry parameters: sodium, potassium, calcium, magnesium, chloride, glucose, creatinine, urea or BUN, amylase, bilirubin, AST, ALT, total protein, albumin, lactate dehydrogenase. Part 2A: Number of participants with abnormal thyroid function [ Time Frame: Up to 2 years ]Blood samples will be collected to assess the levels of TSH, T3, or FT3 and FT4. Part 2A: Number of participants with abnormal urine parameters [ Time Frame: Up to 2 years ]Urine samples will be collected to evaluate specific gravity, leucocyte esterase, nitrite, blood, protein, glucose, and ketones. Part 2A: Number of participants with abnormal vital signs [ Time Frame: Up to 2 years ]Blood pressure, pulse rate, respiratory rate and temperature will be assessed. Part 2A: Number of participants with abnormal ECG [ Time Frame: 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 with abnormal physical examination [ Time Frame: Up to 2 years ]Physical examination including weight will be assessed. Part 2A: Number of participants receiving concomitant medications [ Time Frame: Up to 2 years ]Concomitant medications will be recorded. Part 2B: Number of participants with TEAEs [ Time Frame: 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 [ Time Frame: Up to 2 years ]Participants with immune related AEs of interest will be assessed. Part 2B: Number of participants with abnormal hematology parameters [ Time Frame: 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 [ Time Frame: Up to 2 years ]Blood samples will be collected to assess the following chemistry parameters: sodium, potassium, calcium, magnesium, chloride, glucose, creatinine, urea or BUN, amylase, bilirubin, AST, ALT, total protein, albumin, lactate dehydrogenase. Part 2B: Number of participants with abnormal thyroid function [ Time Frame: Up to 2 years ]Blood samples will be collected to assess the levels of TSH, T3, or FT3 and FT4. Part 2B: Number of participants with abnormal urine parameters [ Time Frame: Up to 2 years ]Urine samples will be collected to evaluate specific gravity, leucocyte esterase, nitrite, blood, protein, glucose, and ketones. Part 2B: Number of participants with abnormal vital signs [ Time Frame: Up to 2 years ]Blood pressure, pulse rate, respiratory rate and temperature will be assessed. Part 2B: Number of participants with abnormal ECG parameters [ Time Frame: 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 with abnormal physical examination [ Time Frame: Up to 2 years ]Physical examinations including weight will be assessed. Part 2B: Number of participants receiving concomitant medications [ Time Frame: 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 [ Time Frame: Up to 2 years ]ORR is defined as the proportion of participants achieving complete response (CR) or partial response (PR) as assessed by investigator per RECIST version 1.1 will be evaluated. Part 2B: Cohort F ORR by RECIST version 1.1 [ Time Frame: Up to 2 years ]ORR is defined as the proportion of participants achieving CR or PR as assessed by investigator per RECIST version 1.1 will be evaluated. Part 2B: Cohort A2 ORR by RECIST version 1.1 [ Time Frame: Up to 2 years ]ORR is defined as the proportion of participants achieving CR or PR as assessed by investigator per RECIST version 1.1 will be evaluated. Part 2B: Cohort G ORR by RECIST version 1.1 [ Time Frame: Up to 2 years ]ORR is defined as the proportion of participants achieving CR or PR as assessed by investigator per RECIST version 1.1 will be evaluated. Part 2B: Cohort E ORR by immune related Response Evaluation Criteria in Solid Tumors per irRECIST [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 Outcome Measures : Part 2B: Cohort A1 ORR by independent blinded central review using RECIST version 1.1 [ Time Frame: Up to 2 years ]ORR is defined as the proportion of participants achieving CR or PR as assessed by investigator per RECIST version 1.1 will be evaluated. Part 2B: Cohort F ORR by independent blinded central review using RECIST version 1.1 [ Time Frame: Up to 2 years ]ORR is defined as the proportion of participants achieving CR or PR as assessed by investigator per RECIST version 1.1 will be evaluated. Part 2B: Cohort A1 Immune-related objective response rate (irORR) by irRECIST [ Time Frame: Up to 2 years ]Immune related objective response rate will be evaluated. Part 2B: Cohort A2 irORR by irRECIST [ Time Frame: Up to 2 years ]Immune related objective response rate will be evaluated. Part 2B: Cohort F irORR by irRECIST [ Time Frame: Up to 2 years ]Immune related objective response rate will be evaluated. Part 2B: Cohort G irORR by irRECIST [ Time Frame: Up to 2 years ]Immune related objective response rate will be evaluated. Part 2B: Cohort A1 Duration of response (DOR) based on independent blinded central review using RECIST version 1.1 [ Time Frame: 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 DOR based on independent blinded central review using RECIST version 1.1 [ Time Frame: 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 G DOR based on independent blinded central review using RECIST version 1.1 [ Time Frame: 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 A1 Disease control rate [ Time Frame: Up to 2 years ]Disease control rate is the proportion of participants achieving CR, PR, or SD per RECIST v1.1 based on independent blinded central review. Part 2B: Cohort A2 Disease control rate [ Time Frame: Up to 2 years ]Disease control rate is the proportion of participants achieving CR, PR, or SD per RECIST v1.1 based on independent blinded central review. Part 2B: Cohort F Disease control rate [ Time Frame: Up to 2 years ]Disease control rate is the proportion of participants achieving CR, PR, or SD per RECIST v1.1 based on independent blinded central review. Part 2B: Cohort G Disease control rate [ Time Frame: Up to 2 years ]Disease control rate is the proportion of participants achieving CR, PR, or SD per RECIST v1.1 based on independent blinded central review. Part 2B: Immune related disease control rate [ Time Frame: Up to 2 years ]The proportion of participants achieving CR, PR, or SD per irRECIST based on Investigators' assessment. Part 2B: Immune related duration of response [ Time Frame: Up to 2 years ]The time from first documentation of CR or PR by irRECIST until the time of first documentation of PD (subsequently confirmed) per irRECIST based on Investigators' assessment. Part 2B: Progression free survival [ Time Frame: Up to 2 years ]The time from date of first dose to the earlier date of assessment of progression or death by any cause in the absence of progression based on: (1) the time of first documentation of PD per RECIST v1.1 (for Cohorts A1, A2, F, and G only); and (2) the time of first documentation of PD (subsequently confirmed) per irRECIST. Part 2B: Overall survival [ Time Frame: Up to 2 years ]The time from date of first dose of study treatment to the date of death by any cause. Part 1: Area under the concentration-time curve from time 0 to last (AUC,0-last) assessment of dostarlimab [ Time Frame: Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504 and 672 hours post dose ]Blood samples for determination of serum levels of dostarlimab will be collected. Part 1: Area under the concentration-time curve from time 0 to infinity (AUC, 0-infinity) of dostarlimab [ Time Frame: Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504,672 hours post dose ]Blood samples for determination of serum levels of dostarlimab will be collected. Part 1: Minimum concentration (Cmin) of dostarlimab [ Time Frame: Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504,672 hours post dose ]Blood samples for determination of serum levels of dostarlimab will be collected. Part 1: Maximum concentration (Cmax) of dostarlimab [ Time Frame: Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504,672 hours post dose ]Blood samples for determination of serum levels of dostarlimab will be collected. Part 1: Clearance (CL) of dostarlimab [ Time Frame: Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504,672 hours post dose ]Blood samples for determination of serum levels of dostarlimab will be collected. Part 1: Volume of distribution (Vz) of dostarlimab [ Time Frame: Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504,672 hours post dose ]Blood samples for determination of serum levels of dostarlimab will be collected. Part 1: Area under the concentration-time curve at steady state (AUC,ss) of dostarlimab [ Time Frame: Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504,672 hours post dose ]Blood samples for determination of serum levels of dostarlimab will be collected. Part 1: Minimum concentration at steady state (Cmin,ss) of dostarlimab [ Time Frame: Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504,672 hours post dose. ]Blood samples for determination of serum levels of dostarlimab will be collected. Part 1: Maximum concentration at steady state (Cmax,ss) of dostarlimab [ Time Frame: Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504,672 hours post dose ]Blood samples for determination of serum levels of dostarlimab will be collected. Part 2A : AUC,0-last assessment of dostarlimab [ Time Frame: Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, and 504 hours post dose Q3W upto 2 years ]Blood samples for determination of serum levels of dostarlimab will be collected. Part 2A: AUC, 0-infinity of dostarlimab [ Time Frame: Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, and 504 hours post dose Q3W upto 2 years ]Blood samples for determination of serum levels of dostarlimab will be collected. Part 2A: Cmin of dostarlimab [ Time Frame: Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, and 504,hours post dose Q3W upto 2 years ]Blood samples for determination of serum levels of dostarlimab will be collected Part 2A: Cmax of dostarlimab [ Time Frame: Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, and 504,hours post dose Q3W upto 2 years ]Blood samples for determination of serum levels of dostarlimab will be collected. Part 2A: CL of dostarlimab [ Time Frame: Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, and 504,hours post dose Q3W upto 2 years ]Blood samples for determination of serum levels of dostarlimab will be collected. Part 2A: Vz of dostarlimab [ Time Frame: Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, and 504 hours post dose Q3W upto 2 years. ]Blood samples for determination of serum levels of dostarlimab will be collected. Part 2A: AUC,ss of dostarlimab [ Time Frame: Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, and 504 hours post dose Q3W upto 2 years ]Blood samples for determination of serum levels of dostarlimab will be collected. Part 2A: Cmin,ss of dostarlimab [ Time Frame: Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, and 504 hours post dose Q3W upto 2 years ]Blood samples for determination of serum levels of dostarlimab will be collected. Part 2A: Cmax,ss of dostarlimab [ Time Frame: Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, and 504 hours post dose Q3W upto 2 years ]Blood samples for determination of serum levels of dostarlimab will be collected. Part 2A : AUC,0-last assessment of dostarlimab [ Time Frame: Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504, 672, 840, and 1008 hours post dose Q6W upto 2 years ]Blood samples for determination of serum levels of dostarlimab will be collected. Part 2A: AUC, 0-infinity of dostarlimab [ Time Frame: Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504, 672, 840, and 1008 hours post dose Q6W upto 2 years ]Blood samples for determination of serum levels of dostarlimab will be collected. Part 2A: Cmin of dostarlimab [ Time Frame: Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504, 672, 840, and 1008 hours post dose Q6W upto 2 years ]Blood samples for determination of serum levels of dostarlimab will be collected. Part 2A: Cmax of dostarlimab [ Time Frame: Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504, 672, 840, and 1008 hours post dose Q6W upto 2 years ]Blood samples for determination of serum levels of dostarlimab will be collected. Part 2A: CL of dostarlimab [ Time Frame: Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504, 672, 840, and 1008 hours post dose Q6W upto 2 years ]Blood samples for determination of serum levels of dostarlimab will be collected. Part 2A: Vz of dostarlimab [ Time Frame: Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504, 672, 840, and 1008 hours post dose Q6W upto 2 years ]Blood samples for determination of serum levels of dostarlimab will be collected. Part 2A: AUC,ss of dostarlimab [ Time Frame: Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504, 672, 840, and 1008 hours post dose Q6W upto 2 years ]Blood samples for determination of serum levels of dostarlimab will be collected. Part 2A: Cmin,ss of dostarlimab [ Time Frame: Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504, 672, 840, and 1008 hours post dose Q6W upto 2 years ]Blood samples for determination of serum levels of dostarlimab will be collected. Part 2A: Cmax,ss of dostarlimab [ Time Frame: Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504, 672, 840 and 1008 hours post dose Q6W upto 2 years ]Blood samples for determination of serum levels of dostarlimab will be collected. Part 2B : AUC,0-last assessment of dostarlimab [ Time Frame: Predose, 0.5 and 1.5 hours post dose ]Blood samples for determination of serum levels of dostarlimab will be collected. Part 2B: AUC, 0-infinity of dostarlimab [ Time Frame: Predose, 0.5 and 1.5 hours post dose ]Blood samples for determination of serum levels of dostarlimab will be collected. Part 2B: Cmin of dostarlimab [ Time Frame: Predose, 0.5 and 1.5 hours post dose ]Blood samples for determination of serum levels of dostarlimab will be collected. Part 2B: Cmax of dostarlimab [ Time Frame: Predose, 0.5 and 1.5 hours post dose ]Blood samples for determination of serum levels of dostarlimab will be collected. Part 2B: CL of dostarlimab [ Time Frame: Predose, 0.5 and 1.5 hours post dose ]Blood samples for determination of serum levels of dostarlimab will be collected. Part 2B: Vz of dostarlimab [ Time Frame: Predose, 0.5 and 1.5 hours post dose ]Blood samples for determination of serum levels of dostarlimab will be collected. Part 2B: AUC,ss of dostarlimab [ Time Frame: Predose, 0.5 and 1.5 hours post dose ]Blood samples for determination of serum levels of dostarlimab will be collected. Part 2B: Cmin,ss of dostarlimab [ Time Frame: Predose, 0.5 and 1.5 hours post dose ]Blood samples for determination of serum levels of dostarlimab will be collected. Part 2B: Cmax,ss of dostarlimab [ Time Frame: Predose, 0.5 and 1.5 hours post dose ]Blood samples for determination of serum levels of dostarlimab will be collected. Eligibility CriteriaGo to Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information Information from the National Library of Medicine Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies. Layout table for eligibility information Ages Eligible for Study: 18 Years and older (Adult, Older Adult) Sexes Eligible for Study: All Accepts Healthy Volunteers: No Criteria Inclusion Criteria: 2b1af7f3a8