Tremelimumab
- Generic Name
- Tremelimumab
- Brand Names
- Imjudo, Tremelimumab AstraZeneca
- Drug Type
- Biotech
- CAS Number
- 745013-59-6
- Unique Ingredient Identifier
- QEN1X95CIX
- Background
Tremelimumab, formerly known as ticilimumab, is a fully human IgG2 monoclonal antibody directed against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4). CTLA-4 is a cell surface receptor expressed on activated T cells to act as a negative regulator for T cells. By binding to CTLA-4, tremelimumab enhances T cell-mediated killing of tumours and reduces tumour growth. Because CTLA-4 is an immune checkpoint that plays a vital role in regulating T cell-mediated immune response, tremelimumab is considered an immune checkpoint inhibitor, which is an emerging cancer immunotherapy drug class.
Tremelimumab was first approved by the FDA in October 2022 to be used in combination with durvalumab to treat hepatocellular carcinoma. It is also being investigated in other cancers, such as colon cancer, pancreatic cancer, non-small cell lung cancer (NSCLC), and malignant melanoma. After receiving an EMA Committee for Medicinal Products for Human Use (CHMP) recommendation in December 2022, tremelimumab was approved for combined use with durvalumab.
- Indication
Tremelimumab is indicated for the treatment of adult patients with unresectable hepatocellular carcinoma in combination with durvalumab. It is also indicated in combination with durvalumab and platinum-based chemotherapy for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with no sensitizing epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) genomic tumor aberrations.
- Associated Conditions
- Metastatic Non-Small Cell Lung Cancer, Unresectable Hepatocellular Carcinoma (HCC)
CDSCO Approves AstraZeneca's Protocol Amendments for Durvalumab-Tremelimumab Combination in Advanced Liver Cancer
• India's CDSCO expert committee has approved AstraZeneca's protocol amendment for a Phase III trial evaluating durvalumab and tremelimumab combination as first-line treatment for advanced hepatocellular carcinoma.
• The approval follows AstraZeneca's presentation of protocol amendment version 8.0 dated June 17, 2024, allowing the company to proceed with modifications to their ongoing clinical investigation.
• This development comes alongside CDSCO's separate approval of AstraZeneca's protocol amendment for AZD0901, an antibody-drug conjugate being studied in advanced gastric cancer expressing claudin18.2.
FDA Approves BMS's Opdivo/Yervoy Combination for First-Line Treatment of Advanced Liver Cancer
• Bristol-Myers Squibb's Opdivo (nivolumab) and Yervoy (ipilimumab) combination has received FDA approval for first-line treatment of unresectable or metastatic hepatocellular carcinoma, demonstrating a 21% reduced risk of death compared to standard therapies.
• The CheckMate-9DW trial showed significant survival benefits with a median overall survival of 23.7 months for the immunotherapy combination versus 20.6 months for tyrosine kinase inhibitors, potentially establishing a new standard of care.
• This approval marks a significant advancement for HCC patients, addressing an unmet need in a disease whose incidence has tripled over four decades, though treatment decisions may be influenced by the combination's known toxicity profile.
AstraZeneca Invests $2.5 Billion in Beijing to Establish Sixth Global R&D Center
• AstraZeneca has announced a $2.5 billion investment in Beijing over the next five years to establish its sixth global strategic R&D center, despite ongoing investigations into alleged illegal activities in China.
• The new R&D hub will focus on early-stage research and clinical development enabled by AI and data science, with plans to expand the Beijing workforce from 600 to 1,700 employees.
• As part of the investment, AstraZeneca is forming strategic partnerships with Beijing Cancer Hospital and three Chinese biotech companies—Harbour BioMed, Syneron Bio, and BioKangtai—including its first vaccine manufacturing facility in China.
Study Reveals Factors Influencing Immune Checkpoint Inhibitor Efficacy in Metastatic Colorectal Cancer
• Cleveland Clinic and Moffitt Cancer Center researchers analyzed data from nearly 19,000 metastatic colorectal cancer patients, confirming immune checkpoint inhibitors significantly improve survival in MSI-H tumors compared to chemotherapy alone.
• The study identified specific factors that may enhance immune checkpoint inhibitor efficacy in traditionally unresponsive MSS tumors, including high albumin levels and recent antibiotic use, potentially expanding treatment options.
• Approximately 12.3% of patients with MSS tumors achieved durable responses to immune checkpoint inhibitors, suggesting the need for further research to identify biomarkers that could predict treatment success in this population.
Bladder-Preserving Treatment Shows Promise: Radiation Plus Dual Immunotherapy Achieves 93% Complete Response in MIBC
• A novel combination of radiation therapy with durvalumab and tremelimumab immunotherapy achieved a 93% complete response rate in muscle-invasive bladder cancer patients, offering a promising bladder-preserving alternative.
• The IMMUNOPRESERVE trial demonstrated strong efficacy with 30 out of 32 patients maintaining their bladders after a median follow-up of 27 months, with 84% two-year overall survival rate.
• The treatment regimen showed manageable safety profile with 31% grade 3-4 adverse events, presenting a potential alternative to radical cystectomy for eligible patients.
PADCEV-KEYTRUDA Combination Shows Sustained Survival Benefit in Advanced Urothelial Cancer Trial
• Phase 3 EV-302 trial demonstrates PADCEV plus KEYTRUDA reduces mortality risk by 49% compared to chemotherapy in advanced urothelial cancer patients, with median overall survival of 33.8 months versus 15.9 months.
• The combination therapy showed significant progression-free survival benefit of 12.5 months compared to 6.3 months with chemotherapy, representing a 52% reduction in disease progression risk.
• Extended 12-month follow-up data confirms sustained efficacy across all patient subgroups, including both cisplatin eligible and ineligible patients, with no new safety concerns identified.
CHMP Backs Durvalumab for Limited-Stage SCLC Following Chemoradiation Success
The European Medicines Agency's CHMP has recommended approval of durvalumab (Imfinzi) as monotherapy for limited-stage small cell lung cancer patients whose disease hasn't progressed after chemoradiation therapy. The recommendation is based on the phase 3 ADRIATIC trial results, which demonstrated a 27% reduction in death risk and significant improvement in progression-free survival compared to placebo.
Trump Administration's Foreign Aid Pause Halts Dozens of Global Clinical Trials
• The Trump administration's 90-day pause on foreign aid has led to the shutdown of numerous health initiatives and medical research projects globally.
• Clinical trials in South Asia, Africa, and Latin America have been suspended, leaving thousands without access to ongoing treatment and supervision.
• USAID-funded programs, including malaria control in Uganda and medical supply distribution in Zambia, have been disrupted, impacting vulnerable populations.
• Scientists face difficult choices between violating stop-work orders to care for trial participants and leaving them to face potential harm.
Nivolumab Plus Ipilimumab Shows Promise in Advanced Hepatocellular Carcinoma
• The combination of nivolumab and ipilimumab has shown significantly improved overall survival in patients with unresectable hepatocellular carcinoma (HCC).
• The CheckMate 9DW trial demonstrated a median overall survival of 23.7 months with nivolumab/ipilimumab compared to 20.6 months with lenvatinib or sorafenib.
• The combination therapy also resulted in a higher objective response rate of 36% versus 13% with lenvatinib/sorafenib, indicating better tumor control.
• The FDA has accepted the application for nivolumab plus ipilimumab as a first-line treatment for unresectable HCC, with a decision expected by April 2025.
Durvalumab Shifts Decades Long SOC as First FDA-Approved Immunotherapy Regimen in LS-SCLC
Durvalumab (Imfinzi) has been approved by the FDA as the first immunotherapy regimen for limited-stage small cell lung cancer (LS-SCLC), marking a significant advancement in treatment. The approval is based on the phase 3 ADRIATIC trial results, showing improved overall survival and progression-free survival compared to placebo, with manageable adverse effects.
BMS's Opdivo/Yervoy Combo Shows Survival Benefit in First-line Liver Cancer Treatment
Bristol-Myers Squibb's immunotherapy combination of Opdivo and Yervoy has demonstrated superior survival benefits in first-line hepatocellular carcinoma treatment, with FDA decision expected by April 2024. The therapy showed a 36% objective response rate compared to 13% for standard treatments, potentially offering a new option for patients with unresectable liver cancer.
Luspatercept Plus Lenalidomide Shows Promise in Non-del(5q) Myelodysplastic Syndrome
• A phase 1b trial combining luspatercept and lenalidomide demonstrates safety and preliminary efficacy in patients with non-del(5q) myelodysplastic syndrome (MDS).
• The combination therapy showed a 50% hematologic improvement rate among evaluable patients, with notable red blood cell transfusion independence.
• The study established a recommended phase 2 dose (RP2D) of lenalidomide at 10 mg daily and luspatercept at 1.0 mg/kg every 21 days.
• These findings support further investigation of this combination to improve outcomes for lower-risk MDS patients lacking the del(5q) abnormality.
Lenvatinib Shows Promise as Second-Line Treatment for Advanced Liver Cancer After Immunotherapy
A phase 2 study reveals that lenvatinib (Lenvima) demonstrates efficacy as a second-line treatment for advanced hepatocellular carcinoma patients who progressed after atezolizumab-bevacizumab therapy. The trial met its primary endpoint with a median progression-free survival of 5.4 months and showed a disease control rate of 84%, establishing lenvatinib as a potential standard treatment option in this setting.
AstraZeneca and Daiichi Sankyo Withdraw EU Application for Lung Cancer Drug Datopotamab Deruxtecan
• AstraZeneca and Daiichi Sankyo withdrew their EU marketing application for datopotamab deruxtecan (Dato-DXd) for advanced non-small cell lung cancer following EMA feedback.
• The decision was based on the Phase III TROPION-Lung01 trial results, where Dato-DXd showed improved PFS but not statistically significant overall survival.
• The companies remain committed to developing Dato-DXd for lung cancer, with ongoing trials exploring its potential in various settings.
• A separate application for Dato-DXd for HER2-negative metastatic breast cancer remains under review by the EMA.
BioNTech's Bispecific Antibody BNT-327 Shows Promise in Triple-Negative Breast Cancer
• BioNTech's BNT-327, a bispecific antibody targeting PD-L1 and VEGF, has demonstrated positive early results in patients with triple-negative breast cancer.
• The bispecific antibody builds on the success of checkpoint inhibitors like Keytruda, potentially representing the next generation of immunotherapy drugs.
• Early trial data, presented at the San Antonio Breast Cancer Symposium, suggest BNT-327 could become a critical component in treating triple-negative breast cancer.
• The development of BNT-327 aligns with a broader interest in PD1/PD-L1 and anti-VEGF bispecifics, following promising results from Summit Therapeutics in lung cancer.
Durvalumab Gains Priority Review for Muscle-Invasive Bladder Cancer Treatment
• The FDA has granted priority review to durvalumab (Imfinzi) for muscle-invasive bladder cancer (MIBC), potentially expediting its approval.
• Phase 3 NIAGARA trial data supports the application, showing a 32% reduction in disease progression or recurrence with perioperative durvalumab.
• The Imfinzi regimen also demonstrated a 25% reduction in the risk of death, offering a significant survival benefit.
• Regulatory decisions are anticipated in the second quarter of 2025, with potential implications for MIBC treatment standards.
Imfinzi Approved for Limited-Stage Small Cell Lung Cancer, Redefining Treatment
• The FDA has approved AstraZeneca's Imfinzi (durvalumab) for treating adults with limited-stage small cell lung cancer (LS-SCLC) after platinum-based chemotherapy and radiation therapy.
• The approval was based on the ADRIATIC Phase III trial, which showed a 27% reduction in the risk of death compared to placebo, marking a significant breakthrough.
• Median overall survival improved to 55.9 months with Imfinzi versus 33.4 months with placebo, establishing a new benchmark for LS-SCLC treatment.
• Imfinzi is now the only immunotherapy approved for both limited and extensive-stage small cell lung cancer, underscoring its potential to improve survival rates.
Tagrisso Recommended for EU Approval in Unresectable EGFR-Mutated NSCLC
• The CHMP has recommended Tagrisso (osimertinib) for EU approval in patients with unresectable Stage III EGFR-mutated NSCLC after platinum-based chemoradiotherapy.
• The recommendation is based on the LAURA Phase III trial, which demonstrated a significant improvement in progression-free survival with Tagrisso.
• Tagrisso, a third-generation EGFR-TKI, has shown clinical activity against CNS metastases and is already used in earlier and later stages of EGFR-mutated NSCLC.
• This approval aims to address the unmet need for effective treatments in this specific lung cancer patient population, potentially improving outcomes.
FDA Filing for Datopotamab Deruxtecan in EGFR-Mutated NSCLC
• AstraZeneca and Daiichi Sankyo submitted a BLA to the FDA for accelerated approval of datopotamab deruxtecan in EGFR-mutated NSCLC.
• The submission is based on Phase II TROPION-Lung05 trial data and supported by Phase III TROPION-Lung01 and Phase I TROPION-PanTumor01 trials.
• The companies voluntarily withdrew a previous BLA for nonsquamous NSCLC following FDA feedback.
• Datopotamab deruxtecan, a TROP2-directed antibody-drug conjugate, could offer renewed hope for patients with this challenging disease.
AstraZeneca's China President Detained Amid Widening Investigation into Drug-Related Violations
• AstraZeneca confirms the detention of its China president Leon Wang and investigation of four other executives, causing a 15% drop in company shares and £15 billion market value loss.
• Investigations encompass multiple potential violations, including falsification of genetic test results for Tagrisso eligibility and unauthorized imports of cancer drugs Enhertu, Imfinzi, and Imjudo.
• The probe into AstraZeneca, which recorded $5.9 billion in China sales in 2023, occurs amid broader scrutiny of the healthcare sector by Chinese authorities.
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