Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication IMJUDO is a cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) blocking antibody indicated: • in combination with durvalumab, for the treatment of adult patients with unresectable hepatocellular carcinoma (uHCC). FDA label
Also known as Tremelimumab (Regimen 1), tremelimumab (treme), Tremelimumab monotherapy, tremelimumab (anti-CTLA4), Imjudo, MEDI1123
Tremelimumab · 9 trials · 10 indications
OS is defined as the time from randomisation until the date of death due to any cause.
PFS is defined as time from randomization until progression per RECIST 1.1 as assessed by BICR or death due to any cause
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. ORR is defined as the proportion of all subjects with confirmed PR or CR according to RECIST 1.1.
ORR will include confirmed complete response (CR) + confirmed partial response (PR) and will be determined as per RECIST version 1.1. A confirmed response is defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart.
Time from randomization to death from any cause with patients who were alive at the time of the final analysis or who became lost to follow-up censored at their last date known to be alive.
Objective response rate (ORR) during the initial tremelimumab monotherapy phase was assessed by the site Investigator using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1) and was defined as the percentage of patients with a confirmed overall response of complete response (CR) or partial response (PR) and was based on all treated patients who had measurable disease at baseline (Day 1). 95% confidence intervals (CIs) were calculated using the Clopper Pearson method.
A DLT was defined as treatment-related toxicity that occurred during DLT evaluation period including: any Grade 4 immune-related adverse event (irAE), any Grade 3 colitis or any Grade 3 noninfectious pneumonitis irrespective of duration, any \>= Grade 2 pneumonitis that does not resolve to \<= Grade 1 within 7 days of initiation of maximal supportive care, any other Grade 3 irAE (excluding colitis or pneumonitis) that does not downgrade to Grade 2 within 7 days after onset of the event despite optimal medical management including systemic corticosteroids or does not downgrade to \<= Grade 1 or baseline within 14 days, liver transaminase elevation \> 8 × upper limit of normal (ULN) or total bilirubin \> 5 × ULN, aspartate aminotransferase or alanine aminotransferase \> 3 × ULN with concurrent increase in total bilirubin \> 2 × ULN without evidence of cholestasis or alternative explanations, and any \>= Grade 3 non-irAE (except for the protocol stated conditions).
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. There will be no updated results for this outcome measure at the time of end of study.
Participants with clinically important Common Terminology Criteria for Adverse Events (CTCAE) grade changes to 3 or 4 in hematology and chemistry parameters are reported. There will be no updated results for this outcome measure at the time of end of study.
Vital sign assessment included pulse rate, blood pressure, temperature, weight, and respiratory rate. Vital signs abnormalities recorded as TEAEs are reported. There will be no updated results for this outcome measure at the time of end of study.
Number of participants with ECG abnormalities recorded as TEAEs are reported. There will be no updated results for this outcome measure at the time of end of study.
Overall survival (OS) by treatment arm
To investigate the safety and tolerability of tremelimumab and/ or MEDI4736 when given to Japanese patients
| Arm | Type | Description |
|---|---|---|
| Arm A | EXPERIMENTAL | Tremelimumab , rilvegostomig and bevacizumab |
| Arm B | EXPERIMENTAL | Rilvegostomig, and bevacizumab |
| Arm C | ACTIVE_COMPARATOR | Atezolizumab, and bevacizumab |
| Tremelimumab | EXPERIMENTAL | Tremelimumab 750 mg IV Day 1 of each 28 day cycle. Up to 7 cycles. |
| Single Tremelimumab with Regular Interval Durvalumab plus Gemcitabine and Cisplatin | EXPERIMENTAL | Cycles 1 through 8 will be in 3-week intervals and Cycles 9+ will be in 4-week intervals. Tremelimumab is administered at 300mg intravenously once at Cycle 1. Durvalumab is administered at 1500mg intravenously every 3 weeks for Cycles 1-8, then every 4 weeks for Cycles 9+. Gemcitabine is administered at 1000mg/m\^2 intravenously on Day 1 and Day 8 of Cycles 1-8 only. Cisplatin is administered at 25mg/m\^2 intravenously on Day 1 and Day 8 of Cycles 1-8 only. |
| Best Supportive Care | ACTIVE_COMPARATOR | Best supportive care available |
| Durvalumab plus Tremelimumab and Best Supportive Care | EXPERIMENTAL | Tremelimumab 75mg IV 60 minutes Day 1, cycles 1-4 Durvalumab 1500mg IV 60 minutes Day 1 every 28 days. Plus best supportive care |
| treme mono to be sequenced to MEDI4736 mono or combination | EXPERIMENTAL | tremelimumab monotherapy, with the option for eligible patients to be sequenced to MEDI4736 monotherapy or MEDI4736 + tremelimumab combination therapy after progressive disease (PD) |
| Part 1: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | EXPERIMENTAL | Participants in Part 1A (safety run-in cohort) and Part 1 B (efficacy-gating cohort) will receive tremelimumab 1 mg/kg every 4 weeks (Q4W) 4 doses and durvalumab 20 mg/kg Q4W until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first. |
| Parts 2 and 3: Durvalumab 1500 mg | EXPERIMENTAL | Participants will receive durvalumab 1500 mg Q4W until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first. |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | EXPERIMENTAL | Participants will receive tremelimumab 300 mg 1 dose and durvalumab 1500 mg Q4W until confirmed progressive disease, withdrawal of consent, lost to follow, or development of other reason for treatment discontinuation, whichever occurs first. |
| Parts 2 and 3: Tremelimumab 750 mg | EXPERIMENTAL | Participants will receive tremelimumab 750 mg Q4W 7 doses followed by every 12 weeks (Q12W) until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first. |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | EXPERIMENTAL | Participants will receive tremelimumab 75 mg Q4W 4 doses and durvalumab 1500 mg Q4W until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first. Participant recruitment to this arm was closed following protocol amendment 5. |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | EXPERIMENTAL | Participants will receive durvalumab 1120 mg and bevacizumab 15 mg/kg every 3 weeks (Q3W) until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first |
| China Cohort: Durvalumab 20 mg/kg | EXPERIMENTAL | Participants will receive durvalumab 20 mg/kg Q4W until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first. |
| China Cohort: Tremelimumab 10 mg/kg | EXPERIMENTAL | Participants will receive tremelimumab 10 mg/kg Q4W 7 doses followed by Q12W until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first. |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | EXPERIMENTAL | Participants will receive tremelimumab 1 mg/kg Q4W 4 doses and durvalumab 20 mg/kg Q4W until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first. |
| Placebo | PLACEBO_COMPARATOR | Placebo |
| Part A | OTHER | Dose escalation of tremelimumab mono therapy for advanced solid malignancies |
| Part B | OTHER | Combination therapy of tremelimumab and MEDI4736 for advanced solid malignancies |
| Part C | OTHER | Fixed dose of tremelimumab for malignant mesothelioma |
| Name | Type | Description |
|---|---|---|
| Tremelimumab | DRUG | IV therapy |
| Rilvegostomig | DRUG | IV therapy |
| Bevacizumab | DRUG | IV therapy |
| Atezolizumab | DRUG | IV therapy |
| Durvalumab | DRUG | Durvalumab IV (intravenous) |
| Transarterial Chemoembolization (TACE) | PROCEDURE | TACE (chemo and embolic agent injection into the hepatic artery) |
| Lenvatinib | DRUG | Lenvatinib (oral) |
| Gemcitabine | DRUG | Gemcitabine is administered at 1000mg/m\^2 intravenously on Day 1 and Day 8 of Cycles 1-8 only. |
| Cisplatin | DRUG | Cisplatin is administered at 25mg/m\^2 intravenously on Day 1 and Day 8 of Cycles 1-8 only. |
| Best Supportive Care | OTHER | - |
| Tremelimumab monotherapy | BIOLOGICAL | IV infusion |
| MEDI4736 monotherapy | BIOLOGICAL | IV infusion |
| MEDI4736 + tremelimumab combination therapy | BIOLOGICAL | IV infusion |
| Placebo | DRUG | Placebo is to be administered as an IV solution, followed by observation. |
| MEDI4736 | DRUG | MEDI4736 administered intravenously. |
Inclusion Criteria: * Locally advanced or metastatic and/or unresectable HCC * WHO/ECOG performance status of 0 or 1 * BCLC stage B (that is not eligible for locoregional therapy) or stage C. * Child-Pugh Score class A * At least one measurable target lesion * Participants with active HBV infection...
Tremelimumab is an investigational monoclonal antibody being developed by AstraZeneca PLC (ticker AZN) for several cancer types, including hepatocellular carcinoma, colorectal cancer, urothelial bladder cancer, and malignant mesothelioma. It is designed to target CTLA4 and is being studied both as a monotherapy and in combination with durvalumab.
Tremelimumab is being studied in clinical trials for the treatment of multiple cancers, including colorectal cancer, combined hepatocellular and cholangiocarcinoma, hepatocellular carcinoma, advanced solid malignancies, unresectable pleural or peritoneal malignant mesothelioma, and urothelial bladder cancer. It is not yet approved for any indication and remains investigational.
Tremelimumab targets CTLA4, a protein that acts as an inhibitor of T cell activation. By binding to CTLA4, tremelimumab is designed to block its inhibitory signal and enhance the immune system's ability to attack cancer cells. It is classified as a CTLA4 inhibitor.
Tremelimumab is being developed by AstraZeneca PLC, which trades under the ticker symbol AZN. AstraZeneca is conducting multiple clinical trials of tremelimumab, both as a single agent and in combination with other therapies such as durvalumab.
Tremelimumab is in Phase 2 of clinical development. It is an investigational agent and has not been approved by the FDA for any indication. The Phase 2 program includes studies in urothelial carcinoma and combined hepatocellular-cholangiocarcinoma, among other cancers.
Tremelimumab is being evaluated in several clinical trials, including NCT06921785, a Phase 3 study in hepatocellular carcinoma; NCT06855225, a Phase 2 study in combined hepatocellular-cholangiocarcinoma; NCT05301842, a Phase 3 study in locoregional hepatocellular carcinoma; and NCT03557918, a completed Phase 2 trial in urothelial cancer.