Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Dostarlimab (TSR-042)
Dostarlimab · 21 trials · 56 indications
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.
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).
The proportion of patients with an objective response at the completion of their follow-up (truncated at 24 months), among all eligible patients. An objective response will be defined as the best overall response of complete response (CR) or partial response (PR) assessed by investigators using validated criteria (i.e. RECIST 1.1)
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.
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.
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.
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 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.
Second primary invasive cancer must be centrally histologically confirmed
Overall response rate is defined as the number of patients with best overall response of complete response or partial response divided by total number of participants by immune Response Evaluation Criteria in Solid Tumors (iRECIST) 1.1.
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.
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.
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.
Number of participants with dose modifications (missed doses, dose delays and infusion interruptions) is summarized.
Number of participants with dose modifications (missed doses, dose delays and infusion interruptions) is summarized.
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.
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
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.
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.
Number of participants who received Concomitant medications is summarized.
Number of participants who received Concomitant medications is summarized.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
OS is defined as the time from date of randomization to the date of death, irrespective of the cause of death.
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).
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.
Will be defined as a complete response (CR) or partial response (PR), confirmed and unconfirmed, as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 using investigator's review.
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.
Participants with immune related AEs of interest will be assessed.
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).
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.
Number of participants will be assessed.
Number of participants will be assessed.
Participants will be supine or in a semi-recumbent position and rested for approximately 2 minutes before ECGs are recorded.
Concomitant medications will be recorded.
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.
Participants with immune related AEs of interest will be assessed.
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.
Blood samples will be collected to assess the following chemistry parameters: sodium, potassium, calcium, magnesium, creatinine, bilirubin, AST, ALT, and albumin.
Participants will be supine or in a semi-recumbent position and rested for approximately 2 minutes before ECGs are recorded.
Concomitant medications will be recorded.
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.
Participants with immune related AEs of interest will be assessed.
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.
Blood samples will be collected to assess the following chemistry parameters: sodium, potassium, calcium, magnesium, creatinine, bilirubin, AST, ALT, and albumin.
Participants will be supine or in a semi-recumbent position and rested for approximately 2 minutes before ECGs are recorded.
Concomitant medications will be recorded.
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.
ORR is defined as the proportion of participants achieving CR or PR as evaluated by independent blinded central review using 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.
ORR is defined as the proportion of participants achieving CR or PR as evaluated by independent blinded central review using RECIST version 1.1.
ORR is defined as the proportion of participants achieving CR or PR as assessed by investigator per irRECIST will be evaluated.
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.
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.
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.
| Arm | Type | Description |
|---|---|---|
| Dostarlimab | EXPERIMENTAL | - |
| Dostarlimab plus belrestotug | EXPERIMENTAL | - |
| Pembrolizumab plus placebo | ACTIVE_COMPARATOR | - |
| Arm A: Dostarlimab | EXPERIMENTAL | - |
| Arm B: Placebo | PLACEBO_COMPARATOR | - |
| Standard of Care (SOC) | ACTIVE_COMPARATOR | Participants will receive SOC (FOLFOX/CAPEOX) or undergo expectant observation post surgery. |
| Arm 1: Participants receiving dostarlimab + Carboplatin-paclitaxel followed by dostarlimab | ACTIVE_COMPARATOR | - |
| Arm 2: Participants receiving placebo + carboplatin-paclitaxel followed by placebo | PLACEBO_COMPARATOR | - |
| Arm 3: Participants receiving dostarlimab + carboplatin-paclitaxel followed by dostarlimab+niraparib | ACTIVE_COMPARATOR | - |
| Arm 4: Participants receiving placebo + carboplatin-paclitaxel followed by placebo | PLACEBO_COMPARATOR | - |
| Dostarlimab-Carboplatin-Paclitaxel followed by Dostarlimab Monotherapy | EXPERIMENTAL | - |
| Combination of mFOLFIRINOX plus dostarlimab and oral vitamin D3 | EXPERIMENTAL | Patients will be included and treated according to the following treatment regimen: * Intra-venous (i.v) dostarlimab: day1 - d21: 500mg IV q3Weeks (cycle 1 to cycle 4) then 1000 mg IV q6Weeks (from cycle 5 onwards) * Oral vitamin D3 8000 IU/d for 14 days, then 4000IU/d * mFOLFIRINOX d1, d15, d29 is administered as follow: oxaliplatin 85 mg/m2 on day1, IV infusion over 2 h, immediately followed by folinic acid 400 mg/m2 or calcium levofolinate 200 mg/m2 given as a 2-h IV infusion, with the addition of irinotecan 180 mg/m2 as per dose-level given as a 90-min intravenous infusion through a Y-connector immediately followed by 5- fluorouracil 2400 mg/m2 over 46 h continuous infusion (cycle 1 to cycle 4). From cycle 5, the mFolfirinox will be substituted by LV5FU D1, D15 and D29. |
| Dostarlimab plus CAPEOX | EXPERIMENTAL | Participants will receive dostarlimab plus CAPEOX (chemotherapy). |
| CAPEOX | ACTIVE_COMPARATOR | Participants will receive CAPEOX (chemotherapy). |
| Dostarlimab monotherapy | EXPERIMENTAL | Participants will receive dostarlimab as monotherapy. |
| Standard of care | ACTIVE_COMPARATOR | Patients will receive the standard of care chemotherapy |
| Dostarlimab- Carboplatin-Paclitaxel followed by Dostarlimab Monotherapy | EXPERIMENTAL | - |
| Group A | EXPERIMENTAL | Dostarlimab monotherapy |
| Group B | EXPERIMENTAL | Dostarlimab + Bevacizumab combination therapy |
| Group C | ACTIVE_COMPARATOR | General chemotherapy (one of Pegylated liposomal doxorubicin, Doxorubicin, Paclitaxel, and Gemcitabine) |
| Sub study 1: Dostarlimab and Belrestotug | EXPERIMENTAL | - |
| Sub study 2: Dostarlimab and nelistotug | EXPERIMENTAL | - |
| Sub study 3: Dosarlimab and Belrestotug and nelistotug | EXPERIMENTAL | - |
| Sub study 4: Dostarlimab and remzistotug | EXPERIMENTAL | - |
| No treatment | NO_INTERVENTION | - |
| Dostarlimab and Niraparib treatment | EXPERIMENTAL | Participants will be given 500 mg Dostarlimab IV every 3 weeks for 4 cycles followed by 1000 mg every 6 weeks, along with 200 mg Niraparib by mouth once daily days 1-21 of all cycles. |
| Dostarlimab plus Belrestotug plus Nelistotug | EXPERIMENTAL | - |
| Cohort A (Dostarlimab + Bevacizumab + Niraparib) | EXPERIMENTAL | - |
| Cohort A | EXPERIMENTAL | Three 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 B | EXPERIMENTAL | Three 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. |
| Treatment (niraparib, dostarlimab) | EXPERIMENTAL | Patients receive niraparib PO QD on days 1-28 of cycle 1. Beginning cycle 2, patients receive niraparib PO QD on days 1-21 and dostarlimab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 6, patients receive niraparib PO QD on days 1-42 and dostarlimab IV over 30 minutes on day 1. Cycles repeat every 42 days for up to 24 months in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo biopsy, blood sample collection, and CT or MRI throughout the study. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| Name | Type | Description |
|---|---|---|
| Dostarlimab | BIOLOGICAL | Dostarlimab will be administered. |
| Belrestotug | BIOLOGICAL | Belrestotug will be administered. |
| Pembrolizumab | BIOLOGICAL | Pembrolizumab will be administered. |
| Placebo | DRUG | Placebo will be administered. |
| CAPEOX | DRUG | CAPEOX will be administered. |
| FOLFOX | DRUG | FOLFOX will be administered. |
| Placebo matching dostarlimab | DRUG | Participants will be administered placebo matching dostarlimab |
| Carboplatin | DRUG | Participants will be administered carboplatin |
| Paclitaxel | DRUG | Participants will be administered paclitaxel |
| Niraparib | DRUG | Participants will be administered niraparib |
| Placebo matching Niraparib | DRUG | Participants will be administered placebo matching Niraparib |
| Vitamin D3 (Cholecalciferol) | DRUG | Oral vitamin D3 8000 IU/d for 14 days, then 4000IU/d |
| mFOLFIRINOX Treatment Regimen | DRUG | mFOLFIRINOX d1, d15, d29 cycle 1 to cycle 4 is administered as follow: oxaliplatin 85 mg/m2 on day1, IV infusion over 2 h, immediately followed by folinic acid 400 mg/m2 or calcium levofolinate 200 mg/m2 given as a 2-h IV infusion, with the addition of irinotecan 180 mg/m2 as per dose-level given as a 90-min intravenous infusion through a Y-connector immediately followed by 5- fluorouracil 2400 mg/m2 over 46 h continuous infusion. |
| LV5FU2 | DRUG | folinic acid 400 mg/m2 Or calcium levofolinate 200 mg/m2 2-h IV infusion 5- fluoro-uracil 2400 mg/m2 Over 46 h continuous infusion. From cycle 5 onwards, D1=D43 |
| Chemotherapy | DRUG | * 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. |
| Bevacizumab | DRUG | Intravenous (IV) infusion |
| Doxorubicin | DRUG | Intravenous (IV) infusion |
| Gemcitabine | DRUG | Intravenous (IV) infusion |
| Pegylated liposomal doxorubicin | DRUG | Intravenous (IV) infusion |
| Nelistotug | DRUG | Nelistotug will be administered. |
| Remzistotug | DRUG | Remzistotug will be administered. |
| Belrestotug. | DRUG | Belrestotug will be administered |
| cisplatin plus radiotherapy | DRUG | In the concurrent phase |
| Biopsy | PROCEDURE | Undergo biopsy |
| Biospecimen Collection | PROCEDURE | Undergo blood sample collection |
| Computed Tomography | PROCEDURE | Undergo CT |
| Magnetic Resonance Imaging | PROCEDURE | Undergo MRI |
Inclusion Criteria: * Has histologically confirmed Stage II to III (T3-T4, N0, or T any, N+) locally advanced rectal adenocarcinoma. * Has radiologically and endoscopically evaluable disease. * Has a tumor demonstrating the presence of either: 1. dMMR status; MMR status must be assessed by immun...
Dostarlimab is an investigational monoclonal antibody being studied for several cancers, including ovarian neoplasms, rectal neoplasms, penile carcinoma, non-small cell lung cancer, and head and neck squamous cell carcinoma. It is also being evaluated in recurrent gynecological clear cell carcinoma and resectable colon cancer. Dostarlimab is not yet approved and remains in clinical development.
Dostarlimab targets PDCD1, also known as programmed cell death protein 1 (PD-1), and acts as an antagonist. By blocking PD-1, Dostarlimab is designed to enhance the immune system's ability to fight cancer cells. This mechanism is being investigated across multiple oncology indications.
Dostarlimab is developed by GSK plc, a global biopharma company listed on the stock exchange under the ticker GSK. GSK is conducting clinical trials to evaluate the safety and efficacy of Dostarlimab in various cancer types.
Dostarlimab is in Phase 1 clinical development, with ongoing trials at various stages. While some studies are in Phase 2 and Phase 3, the overall development program is at Phase 1. Dostarlimab is investigational and has not been approved by regulatory authorities.
Dostarlimab is being studied in several trials, including NCT05751629 for recurrent ovarian cancer, NCT05784012 for head and neck squamous cell carcinoma, NCT05855200 for resectable colon cancer, and NCT06023862 for recurrent gynecological clear cell carcinoma. These trials are actively recruiting participants.
Yes, Dostarlimab is also known as TSR-042. Both names refer to the same investigational monoclonal antibody developed by GSK plc. Researchers and clinical trial documents may use either name when referring to this drug.