Tremelimumab Clinical Trials

Tremelimumab is an FDA-approved medication for unresectable hepatocellular carcinoma (HCC) in combination with durvalumab, known as the STRIDE regimen. It is an anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody. This type of drug works by blocking the CTLA-4 protein, which helps to activate the body's immune cells, called T cells, to recognize and fight cancer cells more effectively. By enhancing the immune response, tremelimumab aims to reduce tumor growth.

In addition to its approved use, tremelimumab is currently being investigated in clinical trials for various other cancers. These include colorectal cancer, bladder cancer, breast cancer, advanced solid tumors, melanoma, renal cell carcinoma, and esophageal adenocarcinoma. Many studies are exploring tremelimumab in combination with other immunotherapies, such as durvalumab, or with radiation therapy and chemotherapy, to improve treatment outcomes.

Uses and Conditions Under Study

Tremelimumab is being studied for its potential to treat a range of cancers, primarily by activating the immune system to target cancer cells. Clinical trials involving tremelimumab have enrolled a total of 36,358 participants across 234 trials, with the first trial starting in 2006 and the latest projected to conclude in 2026.

• Liver Cancers: Tremelimumab is extensively studied for liver cancers, including Hepatocellular Carcinoma (HCC), Unresectable Hepatocellular Carcinoma, and Stage IV Hepatocellular Carcinoma AJCC v8. These conditions are the focus of 34 trials. As an approved first-line therapy for unresectable HCC in combination with durvalumab, ongoing research aims to further enhance its effectiveness, often by combining it with radiation therapy or other systemic treatments.
• Gastrointestinal Cancers: This includes Colorectal Cancer, studied in 8 trials, and Esophageal Adenocarcinoma, investigated in 5 trials. For these cancers, tremelimumab is being explored to stimulate an immune response against tumor cells, potentially improving survival rates when used alone or in combination with other therapies.
• Genitourinary Cancers: Tremelimumab is under investigation for Bladder Cancer (6 trials) and Renal Cell Carcinoma (5 trials). In these studies, researchers are evaluating how tremelimumab can help the immune system combat these specific cancer types, often in combination with other checkpoint inhibitors or targeted treatments.
• Other Solid Tumors: The drug is also being studied in Breast Cancer (6 trials), Melanoma (5 trials), and broadly in Advanced Solid Tumors (5 trials). These trials aim to determine tremelimumab's safety and efficacy across different tumor types, often in patients whose cancers have progressed despite previous treatments.

Dosing

Tremelimumab is administered as an intravenous (IV) infusion. The specific dosage and regimen can vary depending on the condition being treated and whether it is used alone or in combination with other medications.

For its FDA-approved use in unresectable hepatocellular carcinoma, tremelimumab is typically given as a single dose of 300 mg intravenously at Cycle 1, as part of the STRIDE regimen with durvalumab. This regimen often involves regular interval dosing of durvalumab alongside the single tremelimumab dose.

In clinical trials, various doses of tremelimumab have been investigated, both as a single agent and in combination with other drugs like durvalumab, chemotherapy, or radiation therapy. Studied doses include 75 mg, 225 mg, 300 mg, and 750 mg. Some trials have also explored weight-based dosing, such as 1 mg/kg, 3 mg/kg, or 10 mg/kg, often in combination with different doses of durvalumab. These studies aim to identify the most effective and safest dosing strategies for various cancer types.

Side Effects

In clinical trials involving 642 patients treated with Tremelimumab, the most commonly reported side effect was diarrhea. 30.4% of patients taking Tremelimumab experienced diarrhea, compared to 12.6% on placebo. Other common side effects reported more frequently with Tremelimumab than with placebo included:

• Decreased appetite: 24.0% on Tremelimumab vs 17.4% on placebo
• Pruritus (itching): 21.3% on Tremelimumab vs 7.5% on placebo
• Nausea: 21.2% on Tremelimumab vs 14.8% on placebo
• Rash: 16.2% on Tremelimumab vs 6.6% on placebo
• Vomiting: 12.9% on Tremelimumab vs 7.3% on placebo

Some side effects were reported at similar or slightly lower rates with Tremelimumab compared to placebo. For instance, fatigue was reported by 19.0% of patients on Tremelimumab and 20.5% on placebo, and constipation was reported by 14.2% of patients on Tremelimumab and 17.4% on placebo.

Clinical Trial Results

Clinical trials have evaluated Tremelimumab as a single agent and in combination with other treatments across various cancer types.

Rollover Study (NCT00378482)

A rollover study allowed patients who had previously received Tremelimumab in other trials to continue accessing the medication. In this study, the median disease-free survival was 3.0 days. Regarding safety, 4 participants experienced Grade 3 or 4 Tremelimumab-related adverse events, 6 participants had hypersensitivity reactions, and 4 participants experienced serious adverse events.

Prostate Cancer (NCT00702923)

In a study of Tremelimumab (also known as CP-675,206) combined with short-term androgen deprivation for Stage D0 prostate cancer, 6 participants receiving 3 mg/kg of CP-675,206 and 5 participants receiving 6 mg/kg experienced PSA recurrence. Cancer antigen-specific immune responses were observed in 8 participants in the 3 mg/kg group and 6 participants in the 6 mg/kg group. An increase in PSA doubling time was noted in 2 participants in the 3 mg/kg group and 1 participant in the 6 mg/kg group.

Malignant Mesothelioma (NCT01843374)

A randomized, double-blind study compared Tremelimumab to placebo in patients with unresectable malignant mesothelioma. The overall response rate was 4.5% for patients on Tremelimumab, compared to 1.1% for those on placebo. The durable disease control rate was 16.8% for Tremelimumab, versus 11.6% for placebo. However, the overall survival rate at 18 months was 17.4% for Tremelimumab and 18.2% for placebo. The median progression-free survival was 2.69 months for Tremelimumab and 2.76 months for placebo, while the median duration of response was 4.8 months for Tremelimumab and 5.57 months for placebo.

Liver Cancer (NCT01853618)

This study investigated Tremelimumab in combination with chemoembolization or ablation for liver cancer across several arms. Median overall survival ranged from 6 months (Tremelimumab + RFA) to 13.1 months (Tremelimumab + TACE or Tremelimumab + Cryoablation). Median progression-free survival ranged from 3.4 months (Tremelimumab + RFA) to 8.6 months (Tremelimumab + Cryoablation).

Combination Therapy (NCT01975831)

A Phase 1 study evaluated durvalumab in combination with Tremelimumab across various doses and cancer types. Median overall survival ranged from approximately 7.3 months (3 mg/kg durvalumab + 1 mg/kg Tremelimumab) to 21.8 months (3 mg/kg durvalumab + 3 mg/kg Tremelimumab) in the escalation phase. In the expansion phase, median overall survival ranged from approximately 8.8 months (colorectal cancer, non-triple negative breast cancer) to 19.1 months (cervical cancer). Median progression-free survival (per irRC) ranged from approximately 1.4 months (3 mg/kg durvalumab + 1 mg/kg Tremelimumab) to 10.7 months (renal cell carcinoma).

Currently Recruiting Trials

Tremelimumab is currently being investigated in a range of clinical trials, often in combination with other therapies, to explore its potential in treating various cancers. These studies aim to improve treatment outcomes for patients with advanced or unresectable diseases.

• A Phase 2 study, NCT07175441, is evaluating RBS2418 in combination with Tremelimumab plus Durvalumab (known as STRIDE) for advanced unresectable hepatocellular carcinoma (liver cancer). RBS2418 is an immune modulator. This study plans to enroll 220 participants across three arms, testing different dosages of RBS2418 with STRIDE or STRIDE alone.
• The IMMUNO-BIOMAP Trial, NCT07288034, is a Phase 2 study focusing on non-small cell lung cancer (NSCLC) stages IIIB-IV. It aims to identify biomarkers that predict response to initial PD(L)1-based immunotherapy and guide second-line treatment. One arm includes Tremelimumab and Durvalumab. This trial is designed for 535 participants.
• For patients with hepatocellular carcinoma, NCT07489976 is a Phase 2 study investigating a combination of immunotherapy and a liver-directed tumor procedure. The goal is to shrink or control the cancer to potentially make more patients eligible for curative treatments. This study seeks to enroll 41 participants who are at least 18 years old, have HCC beyond UCSF criteria, an ECOG performance status of 2 or less, and Child-Pugh A or B7 liver function.
• A large Phase 3 study, NCT06921785, is comparing rilvegostomig in combination with bevacizumab, with or without Tremelimumab, against atezolizumab plus bevacizumab as a first-line treatment for hepatocellular carcinoma. This global study aims to enroll 1220 participants.
• In biliary tract cancers, a Phase 1 study (NCT06564623) is assessing the safety and immune response of a personalized mutant peptide vaccine (mBTCvax) combined with Durvalumab and Tremelimumab. This trial is enrolling 25 participants who have advanced stage biliary tract cancers after front-line treatment.
• Another study, NCT05932199, is a Phase 1/2 trial for mesothelioma, exploring neoadjuvant Durvalumab and Tremelimumab, either alone or with chemotherapy. The study plans to enroll 52 participants to determine if these combinations improve efficacy for malignant pleural mesothelioma.
• The SERPENTINE trial, NCT06680739, is a Phase 2 study evaluating Durvalumab and Tremelimumab, alone or in combination, for patients with colorectal or endometrial cancer. It specifically targets patients with microsatellite instability-high (MSI-H) tumors and those with microsatellite stable (MSS) tumors. This study aims to enroll 60 participants.

Where to Participate

Clinical trials for Tremelimumab are accessible across a wide geographic area, with studies being conducted at 188 sites in 153 cities across 34 states. This broad reach allows many patients to potentially find a study site near them.

Top participating locations include:

• Atlanta, Georgia (11 sites)
• St Louis, Missouri (8 sites)
• New York, New York (6 sites)
• Baltimore, Maryland (6 sites)
• Des Moines, Iowa (4 sites)
• Dallas, Texas (4 sites)
• Chicago, Illinois (4 sites)
• Pittsburgh, Pennsylvania (4 sites)
• New Haven, Connecticut (4 sites)
• Tampa, Florida (3 sites)

Eligibility for these trials generally includes individuals aged 18 years and older, of all genders. While the focus is on patients with specific medical conditions, some studies may also include healthy volunteers, though children are typically not eligible.

Development Timeline

The journey of Tremelimumab began with its first clinical trial on September 20, 2006. Initially, the drug was explored for conditions such as irritable bowel syndrome with constipation (IBS-C) and hyperphosphatemia, indicating a broad early research scope.

Over time, the development focus for Tremelimumab significantly shifted towards oncology. It has since been investigated across a wide array of cancers, including hepatocellular carcinoma, non-small cell lung cancer, renal cell carcinoma, and biliary tract cancers, among many others. This expansion reflects the growing understanding of its potential as an immunotherapy.

To date, Tremelimumab has been studied in 234 trials, enrolling a total of 36,358 participants. The development pipeline spans various phases:

• Phase 2 studies: 122 trials
• Phase 1 studies: 48 trials
• Phase 1/2 studies: 31 trials
• Phase 3 studies: 20 trials

AstraZeneca has been the primary sponsor, leading 35 trials, with other significant contributions from MedImmune LLC, Canadian Cancer Trials Group, and the National Cancer Institute (NCI). The latest trial is projected to conclude on April 6, 2026, demonstrating ongoing commitment to exploring Tremelimumab's therapeutic applications.