Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Rilvegostomig · 12 trials · 11 indications
Overall Survival is defined as time from randomization until the date of death due to any cause.
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 or death due to any cause (in the absence of progression).
Defined as time from randomization until progression per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR), or death due to any cause.
PFS is defined as time from randomization until progression per RECIST v1.1, or death due to any cause.
Recurrence-free survival (RFS) is defined as the time from randomization until the date of radiological recurrence guided by RECIST 1.1 or death due to any cause, whichever occurs first.
To assess the safety and tolerability
ORR is defined as the proportion of participants who have a confirmed CR (complete response) or confirmed PR (partial response) per RECIST 1.1
the proportion of participants who have a confirmed complete response or confirmed partial response, as determined by the Investigator at local site per RECIST 1.1.
the proportion of participants alive and progression-free at 6 months.
Bioavailability based on AUCtau at first SC dose will be determined.
To assess the safety and tolerability and determine RP2D of the combination of novel anti-cancer agents.
To assess the safety and tolerability and determine RP2D of the combination of novel anti-cancer agents.
The OR is defined as a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR).
The localized activity of injected microdoses will be analyzed using the NanoString GeoMx Digital Spatial Profiler (DSP) and the GeoMx Cancer Transcriptome Atlas to comprehensively profile over 1800 genes simultaneously with spatial resolution to describe tumor biology, the TME, and the immune response signatures of each drug at an injection site. DSP outcomes may be validated via IHC, immunofluorescence, or ISH technique.
| Arm | Type | Description |
|---|---|---|
| Control Arm | ACTIVE_COMPARATOR | Durvalumab IV infusion + chemotherapy combination (Gemcitabine/Cisplatin) |
| Experimental Arm | EXPERIMENTAL | Rilvegostomig IV infusion + chemotherapy combination (Gemcitabine/Cisplatin) |
| Arm A | EXPERIMENTAL | Drug: rilvegostomig |
| Arm B | ACTIVE_COMPARATOR | Drug: Pembrolizumab |
| Arm A: T-DXd + Rilvegostomig | EXPERIMENTAL | T-DXd IV Q3W plus rilvegostomig IV Q3W. Treatment will continue until objective disease progression according to RECIST v1.1 as assessed by the Investigator and confirmed by BICR or until other discontinuation criteria is met, whichever occurs first. |
| Arm B: T-DXd + Pembrolizumab | EXPERIMENTAL | T-DXd IV Q3W plus pembrolizumab IV Q3W. Treatment will continue until objective disease progression according to RECIST v1.1 as assessed by the Investigator and confirmed by BICR or until other discontinuation criteria is met, whichever occurs first. |
| Arm C: Carboplatin + Paclitaxel + Pembrolizumab | ACTIVE_COMPARATOR | Carboplatin, paclitaxel and pembrolizumab administered Q3W during 6 cycles, followed by maintenance with pembrolizumab IV Q6W during 14 cycles. Treatment with pembrolizumab will continue for up to 20 total cycles (approximately 24 months, accounting for combination and maintenance phases) or until other discontinuation criteria is met, whichever occurs first. At the discretion of the investigator, participants may continue to receive carboplatin, paclitaxel and pembrolizumab Q3W for up to 10 cycles. Docetaxel can be used as an alternative to paclitaxel for participants who had a hypersensitivity reaction to paclitaxel with a failed rechallenge (or not amenable to rechallenge), according to the investigator's clinical judgment. |
| Arm C | ACTIVE_COMPARATOR | Rilvegostomig + Trastuzumab + FP (5-FU plus cisplatin) or CAPOX (capecitabine plus oxaliplatin) |
| Sub-study 1, investigate rilvegostomig± ramucirumab in 1L non-AGA NSCLC with PD-L1 ≥50% | EXPERIMENTAL | Participants will receive rilvegostomig ± ramucirumab until RECIST 1.1-defined radiological progression, unacceptable toxicity, withdrawal of consent, or other discontinuation criterion |
| Sub-study 2, investigate rilvegostomig + ramucirumab in 1L non-AGA NSCLC with PD-L1 1-49% | EXPERIMENTAL | Participants will receive rilvegostomig + ramucirumab until RECIST 1.1-defined radiological progression, unacceptable toxicity, withdrawal of consent, or other discontinuation criterion |
| Sub-study 3, investigate Dato-DXd + ramucirumab ± rilvegostomig in 2/3L AGA+ NSCLC | EXPERIMENTAL | Participants will receive Dato-DXd + ramucirumab ± rilvegostomig until RECIST 1.1-defined radiological progression, unacceptable toxicity, withdrawal of consent, or other discontinuation criterion |
| Substudy 1 | EXPERIMENTAL | Volrustomig plus XELOX (oxaliplatin and capecitabine) or FOLFOX (oxaliplatin and 5-FU/CF) |
| Substudy 2 | EXPERIMENTAL | Rilvegostomig plus XELOX (oxaliplatin and capecitabine) or FOLFOX (oxaliplatin and 5-FU/CF) |
| Substudy 3 | EXPERIMENTAL | AZD0901 plus volrustomig and 5-fluorouracil or capecitabine |
| Substudy 4, Cohort 4a1 | EXPERIMENTAL | Sonesitatug vedotin (AZD0901) plus rilvegostomig and 5-fluorouracil or capecitabine |
| Substudy 4, Cohort 4a2 | EXPERIMENTAL | Sonesitatug vedotin (AZD0901) plus rilvegostomig and 5-fluorouracil |
| Substudy 4, Cohort 4b | EXPERIMENTAL | Sonesitatug vedotin (AZD0901) plus capecitabine |
| Part 1 (dose finding): Cohort A - SC Rilvegostomig Dose Level 1 (DL1) and rHu | EXPERIMENTAL | Participants will receive IV rilvegostomig (Dose X) as their first dose of study treatment, followed by subsequent treatments with recombinant human hyaluronidase (rHu) and SC rilvegostomig (DL1) at predefined intervals. |
| Part 1 (dose finding): Cohort B - SC Rilvegostomig DL2 and rHu | EXPERIMENTAL | Participants will receive IV rilvegostomig (Dose X) as their first dose of study treatment, followed by subsequent treatments with rHu and SC rilvegostomig (DL2) at predefined intervals. |
| Part 2 (dose confirmation): SC Rilvegostomig and rHu | EXPERIMENTAL | Participants will receive SC rilvegostomig and rHu. |
| Sub study 2 Part A: Safety run-in | EXPERIMENTAL | Participants with squamous and non-squamous NSCLC will receive combination therapy of rilvegostomig, ramucirumab, and platinum-based chemotherapy to assess the safety and tolerability of this regimen. |
| Sub study 2 Part B: Dose expansion | EXPERIMENTAL | Participants will be randomised 1:1 into one of 2 treatment arms (rilvegostomig + chemotherapy + ramucirumab OR rilvegostomig + chemotherapy) in non-squamous histology cohorts and into a single arm (rilvegostomig + chemotherapy+ ramucirumab) in squamous histology cohorts. |
| Rilvegostomig, Volrustomig, Sabestomig, AZD9592, Pembrolizumab | EXPERIMENTAL | HNSCC patients presenting with a surface accessible lesion who are scheduled for tumor and/or regional node dissection as part of their standard treatment will be injected one to three days prior to surgery using the CIVO device. The planned injection scheme includes: vehicle control and microdoses of rilvegostomig, volrustomig, sabestomig, AZD9592, and pembrolizumab as single agents and AZD9592 drug combinations with the evaluated biologics. |
| Name | Type | Description |
|---|---|---|
| Rilvegostomig | DRUG | Rilvegostomig IV (intravenous) Q3W |
| Durvalumab | DRUG | Durvalumab 1500mg IV (intravenous) Q3W for up to 8 cycles (21days). Then Q4W. |
| Gemcitabine/Cisplatin | DRUG | Gemcitabine/Cisplatin IV (Intravenous) 1000 mg/m2 plus cisplatin 25 mg/m2 on Day 1 and Day 8 of each 21-day cycle |
| Pembrolizumab | BIOLOGICAL | Administered intravenously (IV) on Day 1 of each 21-day cycle |
| Trastuzumab deruxtecan | DRUG | Experimental therapy by intravenous infusion |
| Carboplatin | DRUG | Standard of Care (SoC) chemotherapy by intravenous infusion |
| Paclitaxel | DRUG | Standard of Care (SoC) chemotherapy by intravenous infusion |
| Docetaxel | DRUG | Standard of Care (SoC) chemotherapy by intravenous infusion |
| Trastuzumab | DRUG | Q3W, intravenous infusion |
| 5-fluorouracil | DRUG | Q3W, intravenous infusion |
| Capecitabine | DRUG | BID, oral administration |
| Cisplatin | DRUG | Q3W, intravenous infusion |
| Oxaliplatin | DRUG | Q3W, intravenous infusion |
| Pemetrexed | DRUG | Administered as one intravenously (IV) on Day 1 of each 21-day cycle |
| Nab-paclitaxel | DRUG | Administered intravenously (IV) on Days 1, 8, and 15 of each 21-day cycle up to 4 cycles |
| Placebo | DRUG | Placebo IV (intravenous) Q3W |
| S-1 [Tegafur/Oteracil/gimeracil] | DRUG | S-1 \[Tegafur/Oteracil/gimeracil\] (Oral) BSA (body surface area)-based (40, 50, or 60 mg) BID for 4 weeks on 2 weeks off in 42-day cycles |
| Ramucirumab | DRUG | Ramucirumab will be administered as IV infusion. |
| Dato-DXd | DRUG | Dato-DXd will be administered as IV infusion. |
| Volrustomig | DRUG | an anti PD-1 and anti CTLA-4 bispecific antibody; IV infusion |
| FOLFOX | DRUG | 5-fluorouracil oxaliplatin, leucovorin (levoleucovorin when locally preferred and available) |
| XELOX | DRUG | capecitabine and oxaliplatin |
| AZD0901 | DRUG | an anti Claudin18.2 ADC; IV infusion |
| IV Rilvegostomig | DRUG | Rilvegostomig administered IV. |
| Recombinant Human Hyaluronidase (rHu) | DRUG | rHu administered subcutaneously. |
| SC Rilvegostomig | DRUG | Rilvegostomig administered subcutaneously. |
| SC rilvegostomig + rHu | DRUG | SC rilvegostomig + rHu administered subcutaneously. |
| Sabestomig | BIOLOGICAL | Intratumoral microdose injection by the CIVO device. |
| AZD9592 | BIOLOGICAL | Intratumoral microdose injection by the CIVO device. |
| AZD9592 + Rilvegostomig | COMBINATION_PRODUCT | Intratumoral microdose injection by the CIVO device. |
| AZD9592 + Volrustomig | COMBINATION_PRODUCT | Intratumoral microdose injection by the CIVO device. |
| AZD9592 + Sabestomig | COMBINATION_PRODUCT | Intratumoral microdose injection by the CIVO device. |
| AZD9592 + Pembrolizumab | COMBINATION_PRODUCT | Intratumoral microdose injection by the CIVO device. |
Key inclusion Criteria: * Histologically confirmed adenocarcinoma of the biliary tract, including intra-hepatic or extra-hepatic cholangiocarcinoma (CCA) and gallbladder carcinoma (GBC). * Unresectable locally advanced or metastatic BTC, previously untreated in the advanced disease setting * Known ...