Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Volrustomig · 10 trials · 14 indications
Number of participants who received at least one dose of study treatment will be assessed.
The PFS is defined as the time from randomization until radiological progression or death due to any cause (in the absence of progression).
The OS is defined as the time from randomization until the date of death due to any cause.
PFS is defined as time from randomization until first objective radiological progression per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR), or death due to any cause (in the absence of progression). The analysis will include all randomized participants with PD-L1 expressing tumors.
OS is defined as the time from randomization until the date of death due to any cause.
PFS is defined as the time from randomization until radiological progression per RECIST 1.1 as assessed by BICR, or death due to any cause (in the absence of progression), in PD-L1-negative participants.
OS is defined as the time from randomization until the date of death due to any cause, in PD-L1-negative participants.
PFS is defined as the time from date of randomization until RECIST 1.1- defined radiological progression or histopathologically confirmed progression as assessed by the Investigator or death due to any cause, whichever occurs earlier.
PFS24 is defined as the Kaplan-Meier estimate of PFS at 24 months per RECIST 1.1 or histopathologically confirmed progression as assessed by the Investigator or death due to any cause, whichever occurs earlier.
PFS is defined as the time from randomization until progression per Response Evaluation Criteria in Solid Tumours, Version 1.1 (RECIST 1.1) or death due to any cause.
Number of participants who received at least one dose of study treatment will be assessed.
The safety and tolerability of volrustomig in combination with other anticancer drugs in participants with specified solid tumors will be assessed.
ORR is defined as the percentage of participants who have a confirmed complete response (CR) or confirmed partial response (PR), as per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1).
Confirmed ORR is defined as the proportion of participants who have a confirmed CR or confirmed PR, as determined by Investigator per RECIST 1.1.
Number of participants with adverse events and with serious adverse events including abnormal clinical observations, abnormal Electrocardiogram (ECG) parameters, abnormal laboratory assessments and abnormal vital signs that changed from baseline.
| Arm | Type | Description |
|---|---|---|
| Arm 1A (Volrustomig Dose 1 + Casdatifan) | EXPERIMENTAL | Participants will receive dose 1 of volrustomig in combination with casdatifan. |
| Arm 1B (Volrustomig Dose 2 + Casdatifan) | EXPERIMENTAL | Participants will receive dose 2 of volrustomig in combination with casdatifan. |
| Arm 3A (Volrustomig Dose X + Casdatifan) | EXPERIMENTAL | Participants will receive Volrustomig at the dose to be determined in the Phase Ib part of the study, in combination with casdatifan. |
| Arm 3B (Volrustomig Dose 1) | EXPERIMENTAL | Participants will receive dose 1 of volrustomig. |
| Arm 3C (Nivolumab + Ipilimumab) | ACTIVE_COMPARATOR | Participants will receive nivolumab plus ipilimumab as standard of care treatment. |
| Study Arm | EXPERIMENTAL | Participants in this arm will receive volrustomig. |
| Observation Arm | NO_INTERVENTION | Patients in this arm will undergo observation. |
| Volrustomig + Carboplatin + pemetrexed | EXPERIMENTAL | Volrustomig in combination with carboplatin plus pemetrexed |
| Investigator's choice of standard care | ACTIVE_COMPARATOR | The investigator's choice of nivolumab plus ipilimumab or platinum plus pemetrexed chemotherapy for participants with epithelioid histology, and nivolumab plus ipilumab for participants with non-epithelioid histology. |
| Arm 1 | EXPERIMENTAL | Volrustomig plus histology-specific chemotherapy (carboplatin plus either pemetrexed or paclitaxel) via iv infusion |
| Arm 2 | ACTIVE_COMPARATOR | Pembrolizumab plus histology-specific chemotherapy (carboplatin plus either pemetrexed or paclitaxel) via iv infusion |
| Volrustomig | EXPERIMENTAL | Volrustomig |
| Placebo | PLACEBO_COMPARATOR | Placebo |
| Volrustomig + FOLFIRI+ Bevacizumab group (Arm A) | EXPERIMENTAL | Participants will receive FOLFIRI and bevacizumab together with volrustomig. |
| FOLFIRI+ BEVACIZUMAB group (Arm B) | ACTIVE_COMPARATOR | Partcipants will receive FOLFIRI and bevacizumab. |
| Substudy 1: Arm 1A: Volrustomig dose regimen 1 + Carboplatin and Pemetrexed | EXPERIMENTAL | Volrustomig priming dose followed by volrustomig dosing regimen 1 in combination with carboplatin and pemetrexed. |
| Substudy 1: Arm 1B: Volrustomig dose regimen 2 + Carboplatin and Pemetrexed | EXPERIMENTAL | Volrustomig priming dose followed by volrustomig dosing regimen 2 in combination with carboplatin and pemetrexed. |
| Substudy 2: Arm 2A: Volrustomig dose regimen 2 +Ramucirumab + Carboplatin + Pemetrexed or Paclitaxel | EXPERIMENTAL | Volrustomig priming dose followed by volrustomig dosing regimen 2 in combination with ramucirumab and histology-specific chemotherapy (carboplatin+ either pemetrexed or paclitaxel). |
| Sub-study 1 | EXPERIMENTAL | Volrustomig monotherapy |
| Sub-study 2 | EXPERIMENTAL | Volrustomig monotherapy |
| Sub-study 3 Arm A | EXPERIMENTAL | Volrustomig in combination with carboplatin plus paclitaxel |
| Sub-study 3 Arm B | EXPERIMENTAL | Volrustomig in combination with carboplatin plus paclitaxel |
| Sub-study 3 Arm C | EXPERIMENTAL | Volrustomig in combination with 5-FU plus platinum |
| Sub-study 4 Arm A | EXPERIMENTAL | Volrustomig in combination with cisplatin + 5-FU |
| Sub-study 4 Arm B | EXPERIMENTAL | Volrustomig in combination with cisplatin + paclitaxel |
| Sub-study 5 | EXPERIMENTAL | Volrustomig monotherapy |
| Cohort 1A | EXPERIMENTAL | Volrustomig monotherapy |
| Cohort 1B | EXPERIMENTAL | Volrustomig combination with bevacizumab |
| Cohort 1C | EXPERIMENTAL | Volrustomig combination with lenvatinib |
| Cohort 2A | EXPERIMENTAL | Rilvegostomig combination with Gemcitabine and Cisplatin |
| Cohort 2B | EXPERIMENTAL | Volrustomig combination with Gemcitabine and Cisplatin |
| Cohort 1D | EXPERIMENTAL | Volrustomig combination with rilvegostomig and bevacizumab |
| Cohort 1E | EXPERIMENTAL | Rilvegostomig combination with bevacizumab |
| Name | Type | Description |
|---|---|---|
| Volrustomig | DRUG | Volrustomig will be administered as an intravenous (IV) infusion. |
| Casdatifan | DRUG | Casdatifan will be administered orally. |
| Nivolumab | DRUG | Nivolumab will be administered as an IV infusion. |
| Ipilimumab | DRUG | Ipilimumab will be administered as an IV infusion. |
| Pemetrexed | DRUG | Alimta: Administered as IV infusion |
| Carboplatin | DRUG | Paraplatin: Administered as IV infusion |
| Cisplatin | DRUG | Platinol: Administered as IV infusion |
| Pembrolizumab | DRUG | Pembrolizumab |
| Paclitaxel | DRUG | Paclitaxel |
| Placebo | OTHER | IV Infusion |
| FOLFIRI (Fluorouracil (5-FU), leucovorin, irinotecan) | DRUG | FOLFIRI will be administered as IV infusion. |
| Bevacizumab | DRUG | Bevacizumab will be administered as IV infusion. |
| Ramucirumab | DRUG | Participants will receive ramucirumab via IV infusion. |
| 5-FU | DRUG | IV Infusion |
| Lenvatinib | DRUG | Daily use per oral (8 mg capsules/day for participants \< 60 kg or 12 mg/day for participants ≥ 60 kg) of 21 day cycle. Number of Cycles: until disease progression or unacceptable toxicity develops. |
| Rilvegostomig | DRUG | anti- PD-1 and TIGIT bispecific antibody |
| Gemcitabine | DRUG | 1000 mg/m2, IV infusion |
Inclusion Criteria: * Histologically or cytologically confirmed RCC with clear cell component. * Advanced/metastatic RCC or recurrent disease that has not previously been treated with systemic therapy in the 1L setting. * Karnofsky Performance Status ≥ 70%. * Provision of acceptable tumor sample. *...