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Tremelimumab

Phase 3

Hepatocellular Carcinoma | Monoclonal antibody | Oncology |AstraZeneca PLC|Last Updated: Jul 15, 2026

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Trial Design
RandomizedCONTROLLEDDMC
Total Trials3
Total Enrollment2,413
FDA Designations
No designations recorded
Clinical trial landscape

Tremelimumab · 10 trials · 9 indications

Phase 3 2Phase 2 5Phase 1 3
NCT06921785Phase III Study of Rilvegostomig in Combination With Bevacizumab With or Without Tremelimumab as First-line Treatment of Hepatocellular CarcinomaHepatocellular Carcinoma
RECRUITING1,220 Analytics
NCT05301842Evaluate Durvalumab and Tremelimumab +/- Lenvatinib in Combination With TACE in Patients With Locoregional HCCHepatocellular Carcinoma
ACTIVE NOT_RECRUITING760 Analytics
PHASE3RECRUITING
Phase III Study of Rilvegostomig in Combination With Bevacizumab With or Without Tremelimumab as First-line Treatment of Hepatocellular Carcinoma
Hepatocellular CarcinomaUnlock trial analytics
PHASE3ACTIVE NOT_RECRUITING
Evaluate Durvalumab and Tremelimumab +/- Lenvatinib in Combination With TACE in Patients With Locoregional HCC
Hepatocellular CarcinomaUnlock trial analytics
Study Endpoints
Primary Endpoints
To demonstrate the efficacy of Arm A relative to Arm C by assessment of OS in participants with advanced HCC
Up to approximately 6 years

OS is defined as the time from randomisation until the date of death due to any cause.

Progression Free Survival (PFS) for Arm A vs Arm C
Approximately 5 years

PFS is defined as time from randomization until progression per RECIST 1.1 as assessed by BICR or death due to any cause

Objective Response Rate
Up to a maximum of 12 months

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.

Confirmed objective response rate (ORR)
24 months

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.

Overall Survival
24 months

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.

Number of Participants With Dose Limiting Toxicities (DLTs)
From Day 1 to Day 28 after first dose of study drug

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).

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)

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.

Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters
From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)

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.

Number of Participants With Abnormal Vital Signs Reported as TEAEs
From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)

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 Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events
From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)

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)
3 years.

Overall survival (OS) by treatment arm

Phase 1: Determine the recommended phase 2 dose (RP2D) from BCG-unresponsive non-muscle invasive bladder cancer (NMIBC)
6 months

Determine the recommended phase 2 dose (RP2D) from BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) patients treated with each of the following immunotherapy study regimens: Durvalumab (cohort 1) Durvalumab + intravesical BCG (cohort 2) Durvalumab + radiation (cohort 3) Durvalumab + intravesical Gemcitabine + intravesical Docetaxel (cohort 4) Durvalumab + Tremelimumab + intravesical Gemcitabine + intravesical Docetaxel (cohort 5) Intravesical NAI + intravesical Gemcitabine (cohort 6) Intravesical NAI + intravesical Gemcitabine + intravesical Docetaxel (cohort 7) Subcutaneous NAI + intravesical NAI + intravesical Gemcitabine + intravesical Docetaxel (cohort 8) The RP2D of each immunotherapy study arm is defined as the dose level at which \< 2 out of 6, \< 4 out of 9, or \< 5 out of 12 patients enrolled within an individual study arm experience dose-limiting toxicity.

Phase 2: Determine the complete response rate within individual phase 2 expansion cohorts of BCG-unresponsive, BCG-relapsing/persistent, and high-risk BCG-naïve NMIBC subjects treated with each study regimen
6 months

The complete response rate within each study arm is defined as the proportion of patients within each arm that demonstrate no evidence of recurrent or persistent high grade urothelial carcinoma of the bladder of any stage at any post-treatment disease assessment.

Adverse event
From time of informed consent to 90 days after the last dose

To investigate the safety and tolerability of tremelimumab and/ or MEDI4736 when given to Japanese patients

safety and tolerability of the association between Gefitinib (fixed dose) and Tremelimumab (dose escalation)
Up to 42 days

The primary objective of this phase 1 study is to determine the safety and tolerability of oral Gefitinib in combination with three escalating doses of Tremelimumab and to establish a recommended phase 2 dose. Overall safety profile will be characterized by type, frequency, severity (graded using the National Cancer Institute Common Terminology Criteria for Adverse Events \[NCICTCAE\] Version 4.03), timing of adverse events and laboratory abnormalities in the first and in the following cycles

Secondary Endpoints
To demonstrate the efficacy of Arm B relative to Arm C by assessment of OS in participants with advanced HCC
Up to approximately 6 years
To further demonstrate the efficacy of Arm A relative to Arm C and Arm B relative to Arm C in participants with advanced HCC
Up to approximately 6 years
To demonstrate the efficacy of Arm A relative to Arm B in participants with advanced HCC
Up to approximately 6 years
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Study Design & Arms
AllocationRANDOMIZED
MaskingSINGLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Arm AEXPERIMENTALTremelimumab , rilvegostomig and bevacizumab
Arm BEXPERIMENTALRilvegostomig, and bevacizumab
Arm CACTIVE_COMPARATORAtezolizumab, and bevacizumab
TremelimumabEXPERIMENTALTremelimumab 750 mg IV Day 1 of each 28 day cycle. Up to 7 cycles.
Single Tremelimumab with Regular Interval Durvalumab plus Gemcitabine and CisplatinEXPERIMENTALCycles 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 CareACTIVE_COMPARATORBest supportive care available
Durvalumab plus Tremelimumab and Best Supportive CareEXPERIMENTALTremelimumab 75mg IV 60 minutes Day 1, cycles 1-4 Durvalumab 1500mg IV 60 minutes Day 1 every 28 days. Plus best supportive care
Part 1: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kgEXPERIMENTALParticipants 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 mgEXPERIMENTALParticipants 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 mgEXPERIMENTALParticipants 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 mgEXPERIMENTALParticipants 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 mgEXPERIMENTALParticipants 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/kgEXPERIMENTALParticipants 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/kgEXPERIMENTALParticipants 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/kgEXPERIMENTALParticipants 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/kgEXPERIMENTALParticipants 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.
PlaceboPLACEBO_COMPARATORPlacebo
Phase 1: Cohort 1EXPERIMENTALDurvalumab monotherapy
Phase 1: Cohort 2EXPERIMENTALDurvalumab plus BCG
Phase 1: Cohort 3EXPERIMENTALDurvalumab plus External Beam Radiotherapy (EBRT) (BCG re-treatment) - Cross-over to Durvalumab Monotherapy
Phase 1: Cohort 4EXPERIMENTALDurvalumab + Gemcitabine/Intravesical Docetaxel (Gem/Doc) The sequence of administration is flexible to allow for scheduling of both the infusion and intravesical treatments.
Phase 1: Cohort 5EXPERIMENTALNOTE: Cohort 5 was abandoned prior to any patients enrolled. Durvalumab + Tremelimumab + Gem/Doc The sequence of administration is flexible to allow for scheduling of both the infusion and intravesical treatments. For the intravenous medications, durvalumab should be administered first followed by tremelimumab.
Phase 1: Cohort 6EXPERIMENTALIntravesical NAI plus Gemcitabine
Phase 2: Cohort 4 ExpansionEXPERIMENTALDurvalumab + Gemcitabine/Intravesical Docetaxel (Gem/Doc) The sequence of administration is flexible to allow for scheduling of both the infusion and intravesical treatments.
Phase 1: Cohort 7EXPERIMENTALIntravesical NAI plus Gemcitabine and Docetaxel
Phase 1: Cohort 8EXPERIMENTALSubcutaneous NAI plus Intravesical NAI plus Gemcitabine and Docetaxel
Phase 1: Cohort 9EXPERIMENTALAdditional Regimens TBD
Part AOTHERDose escalation of tremelimumab mono therapy for advanced solid malignancies
Part BOTHERCombination therapy of tremelimumab and MEDI4736 for advanced solid malignancies
Part COTHERFixed dose of tremelimumab for malignant mesothelioma
TreatmentEXPERIMENTAL* Cohort 1: Tremelimumab 3 mg/kg every 4 Weeks plus Gefitinib 250 mg/daily, 6 patients (+ 6 patients if 3 mg/kg is the MTD) * Cohort 2: Tremelimumab 6 mg/kg every 4 Weeks plus Gefitinib 250 mg/daily, 6 patients (+ 6 patients if 6 mg/kg is the MTD) * Cohort 3: Tremelimumab 10 mg/kg every 4 Weeks plus Gefitinib 250 mg/daily, 6 patients (+ 6 patients if 10 mg/kg is the MTD)
Interventions
NameTypeDescription
TremelimumabDRUGIV therapy
RilvegostomigDRUGIV therapy
BevacizumabDRUGIV therapy
AtezolizumabDRUGIV therapy
DurvalumabDRUGDurvalumab IV (intravenous)
Transarterial Chemoembolization (TACE)PROCEDURETACE (chemo and embolic agent injection into the hepatic artery)
LenvatinibDRUGLenvatinib (oral)
GemcitabineDRUGGemcitabine is administered at 1000mg/m\^2 intravenously on Day 1 and Day 8 of Cycles 1-8 only.
CisplatinDRUGCisplatin is administered at 25mg/m\^2 intravenously on Day 1 and Day 8 of Cycles 1-8 only.
Best Supportive CareOTHER -
PlaceboDRUGPlacebo is to be administered as an IV solution, followed by observation.
Durvalumab (Cohort 1-3)DRUGDurvalumab 1120 mg intravenously Day 1 every 21 days x 8 cycles.
External Beam Radiotherapy (EBRT)RADIATIONEBRT 6 Gy x 3; Cycle 1 Day 1, 3, and 5
Bacillus Calmette-Guérin (BCG)BIOLOGICALDose level 0 (starting dose) = Full-dose Dose level-1 = 1/3rd-dose BCG. Dose level -1 is expected to be utilized during the phase II portion of the study due to the ongoing and persistent shortage of BCG in the US.
DocetaxelDRUGDocetaxel 37.5 mg intravesical weekly (+/- 2 days) x 6 doses.
Durvalumab (Cohort 4/5)DRUGDurvalumab 1500 mg intravenously Day 1 (+/- 2 days) every 28 days x 6 cycles.
To be determinedOTHEROther regimens to be determined
Intravesical NAI (Cohorts 6-7)DRUGFor all cohorts containing intravesical NAI treatment, starting in Week 1, induction intravesical NAI 400 ug will be administered weekly x 6 doses via a foley catheter into an empty bladder and maintained in the bladder for 60 minutes.
Subcutaneous NAI (Cohort 8)DRUGFor all cohorts containing subcutaneous NAI treatment, starting in Week 1, NAI 10 ug/kg will be administered biweekly for 3 doses via subcutaneous injection.
MEDI4736DRUGMEDI4736 administered intravenously.
GefitinibDRUGOral tablet
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Eligibility Criteria
Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites220

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...

Countries:United StatesAustraliaBrazilCanadaChinaFranceGermanyHong KongIndiaItalyJapanNetherlandsPolandSouth KoreaSpainTaiwanThailandTurkey (Türkiye)United KingdomVietnamBelgiumEgyptMalaysiaMexicoPhilippinesPortugalPuerto RicoSaudi ArabiaSingaporeDenmarkHungaryIsraelRomaniaRussiaSouth AfricaSweden
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Recent Changes (Last 90 Days)
MEDIUMJul 15, 2026NCT03317158Status: RECRUITING → ACTIVE_NOT_RECRUITING
MEDIUMJul 15, 2026NCT03317158Status: RECRUITING → ACTIVE_NOT_RECRUITING
LOWJul 14, 2026NCT06921785lastUpdatePostDate: changed
LOWJul 14, 2026NCT06921785lastUpdatePostDate: changed
LOWJul 13, 2026NCT05301842lastUpdatePostDate: changed
LOWJul 13, 2026NCT05301842lastUpdatePostDate: changed
LOWJun 16, 2026NCT06921785lastUpdatePostDate: changed
LOWJun 16, 2026NCT06921785lastUpdatePostDate: changed
LOWJun 16, 2026NCT06921785lastUpdatePostDate: changed
LOWJun 16, 2026NCT06921785lastUpdatePostDate: changed
LOWJun 11, 2026NCT06921785lastUpdatePostDate: changed
LOWJun 11, 2026NCT06921785lastUpdatePostDate: changed
MEDIUMJun 4, 2026NCT02519348Completion: 2026-04-01 → 2026-12-18
MEDIUMJun 4, 2026NCT02519348Completion: 2026-04-01 → 2026-12-18