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 anti-CTLA4 human monoclonal antibody, Tremelimumab, Imjudo, Tremelimumab-actl, Ticilimumab, CP-675
CP-675,206 · 21 trials · 23 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.
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
The primary endpoint for evaluating progression-free survival (PFS) will be assessed through RECIST 1.1 evaluation.
Tumor evaluation will take place using CT-Chest and abdomen, based on the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) guidelines. The first evaluation will take place 12 weeks after initiating treatment. After this initial scan, tumor evaluation will take place every 8 weeks for the first year. After the first year, tumor evaluation will be done every 12 weeks.
Tumor evaluation will take place using CT-Chest and abdomen, based on the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) guidelines. The first evaluation will take place 12 weeks after initiating treatment. After this initial scan, tumor evaluation will take place every 8 weeks for the first year. After the first year, tumor evaluation will be done every 12 weeks.
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 |
| B | ACTIVE_COMPARATOR | Choice of one or the other Dacarbazine or Temozolomide(CP-675,206) (choice) |
| A | EXPERIMENTAL | - |
| 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 |
| 1 | EXPERIMENTAL | Drug: CP-675,206 (Tremelimumab) |
| 15 mg/kg CP-675,206 | EXPERIMENTAL | - |
| 10 mg/kg | EXPERIMENTAL | pts treated at 10 mg/kg dose level on a monthly regimen |
| 15 mg/kg | EXPERIMENTAL | pts treated at 15 mg/kg dose level on a quarterly regimen |
| Tremelimumab Plus Durvalumab (MEDI4736) in Combination with Concurrent Transarterial Chemoembolizati | EXPERIMENTAL | After the intravenous (IV) administration of 300 mg of tremelimumab and 1,500 mg of durvalumab, transarterial chemoembolization (TACE) will be performed in combination with 1,500 mg of durvalumab via IV infusion every 4 weeks (Q4W) until disease progression (PD) is confirmed. TACE will be carried out 1 to 2 weeks (7 to 14 days) after the administration of tremelimumab + durvalumab, and thereafter, it will be performed as needed at the discretion of the investigator during the treatment period. If additional TACE is performed, there must be at least a 1-week interval between the additional TACE and the administration of durvalumab. |
| Tremelimumab 75 (R1) | EXPERIMENTAL | Run-in phase-1 (R1): n=3 patients will be treated with: * paclitaxel 70 mg/m2 on day 1, 8, 15 of cycles 1-6 * tremelimumab 75 mg on day 1 of cycles 2-6 and then every 12 weeks until week 45 |
| Tremelimumab 225 (R2) | EXPERIMENTAL | Run-in phase-2 (R2): n=3 patients will be treated with: * paclitaxel 70 mg/m2 on day 1, 8, 15 of cycles 1-6 * tremelimumab 225 mg on day 1 of cycles 2-6 and then every 12 weeks until week 45 |
| Tremelimumab vs Tremelimumab+Durvalumab (R3) | EXPERIMENTAL | Run-in phase-3 (R3): n=2 x 3 patients will be randomized over 2 arms: * paclitaxel 70 mg/m2 on day 1, 8, 15 of cycles 1-6 * tremelimumab 750 mg on day 1 of cycles 2-6 and then every 12 weeks until week 45 OR * paclitaxel 70 mg/m2 on day 1, 8, 15 of cycles 1-6 * tremelimumab 75 mg on day 1 of cycles 2-5 * durvalumab 1500 mg on day 1 of cycles 2-12, every four weeks (until week 49) |
| Tremelimumab 300 (R4) | EXPERIMENTAL | Run-in phase-4 (R4): n=3 patients will be treated with: * paclitaxel 70 mg/m2 on day 1, 8, 15 of cycles 1-6 * tremelimumab 300 mg once on day 1 of cycle 2 * durvalumab 1500 mg on day 1 of cycles 2-12, every four weeks (until week 49) |
| Tremelimumab 750 (A) | EXPERIMENTAL | Arm A: * paclitaxel 70 mg/m2 on day 1, 8, 15 of cycles 1-6 * tremelimumab 750 mg on day 1 of cycles 2-6 and then every 12 weeks until week 45 |
| Tremelimumab+Durvalumab (B) | EXPERIMENTAL | Arm B: * paclitaxel 70 mg/m2 on day 1, 8, 15 of cycles 1-6 * tremelimumab 300 mg once on day 1 of cycle 2 * durvalumab 1500 mg on day 1 of cycles 2-12, every four weeks (until week 49) |
| Tremelimumab without paclitaxel (C) | EXPERIMENTAL | Arm C (control arm): • tremelimumab 750 mg on day 1 of cycles 1-5 and then every 12 weeks until week 41 |
| 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 |
| CP-675,206 and gemcitabine | EXPERIMENTAL | - |
| Commercial Formulation | EXPERIMENTAL | Commercial Formulation |
| Current Formulation | EXPERIMENTAL | Current Formulation |
| 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) |
| dacarbazine | DRUG | decarbazine 1000 mg/m2 IV Q 21 days x 12 |
| CP-675,206 | DRUG | CP-675,206 15 mg/kg IV Q 90 days x 4 |
| temozolomide | DRUG | temozolomide 200 mg/m2 orally on Days 1-5 every 28 days x 12 |
| 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. |
| CP-675,206 (Tremelimumab) | DRUG | 15 mg/kg IV every 3 months as long as required |
| Tremelimumab Plus Durvalumab (MEDI4736) | DRUG | Study subjects will receive 1,500 mg of durvalumab intravenously every 4 weeks until PD is observed. However, treatment will be discontinued if unacceptable toxicity, withdrawal of consent, or any other discontinuation criteria are met. Tremelimumab will be administered first, and durvalumab infusion will begin approximately 1 hour (up to 2 hours) after the completion of tremelimumab infusion. The standard infusion time for each drug is 1 hour, but if the infusion is temporarily interrupted, the total duration should not exceed 8 hours at room temperature. |
| Paclitaxel | DRUG | See experimental arm description for more details. |
| CP-675,206 and leuprolide acetate and bicalutamide | DRUG | - |
| leuprolide acetate and bicalutamide | DRUG | - |
| MEDI4736 | DRUG | MEDI4736 administered intravenously. |
| CP-675,206 and gemcitabine | DRUG | Escalating doses of CP-675,206 will be administered by IV infusion on day 1 of each 84-day treatment cycles (doses of 6, 10 and 15 mg/kg are planned). Gemcitabine will be administered by IV infusion, at a fixed dose of 1000 mg/m2 on days 1 (prior to CP-675,206) and again on days 8, 15, 29, 36, 43, 57, 64, and 71. Repeated cycles of gemcitabine and CP-675,206 will be administered until patients develop progressive disease or unacceptable toxicity, or for a maximum of 4 cycles, whichever occurs first. |
| SU011248 | DRUG | SU011248 administered at a dose of 37.5mg/day every day. |
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...
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CP-675,206 is an investigational oncology drug also known as tremelimumab. It is being developed by AstraZeneca PLC (ticker AZN) and has been studied in cancers including non-small-cell lung carcinoma, renal cell carcinoma, colorectal neoplasms, melanoma, and pancreatic cancer. It is in Phase 2 development.
CP-675,206 has been studied in several cancer types, including non-small-cell lung carcinoma, renal cell carcinoma, colorectal neoplasms, malignant melanoma, melanoma, and pancreatic cancer. It remains an investigational agent in Phase 2 development and is not described as approved for any indication.
AstraZeneca PLC, which trades under the ticker AZN, is the developer of CP-675,206. The company has sponsored clinical studies of the agent in pancreatic cancer, melanoma, renal cell carcinoma, and other tumor types.
CP-675,206 is in Phase 2 development. The program includes completed Phase 1 and Phase 2 studies, and no active trials are currently listed. It is an investigational agent and is not described as FDA approved.
Completed studies include NCT00556023, a Phase 1 trial of CP-675,206 with gemcitabine in advanced pancreatic cancer; NCT00431275, a Phase 1 comparison of two CP-675,206 formulations in melanoma; NCT00378482, a Phase 2 rollover study; and NCT00372853, a Phase 1 dose-finding study in metastatic renal cell carcinoma.
Yes, CP-675,206 is also known as tremelimumab. The names refer to the same agent, and combination regimens studied with it include CP-675,206 and gemcitabine, as well as CP-675,206 with leuprolide acetate and bicalutamide.