Imjudo (tremelimumab) plus Imfinzi (durvalumab) - 2 indications

Scroll down for additional information on each indication:

• Adult patients with unresectable hepatocellular carcinoma; approved October of 2022
• Adult patients with Stage IV (metastatic) non-small cell lung cancer (NSCLC); approved November of 2022

General Description

Imjudo (tremelimumab) is a cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) blocking antibody. Imfinzi (durvalumab) is a programmed death-ligand 1 (PD-L1) blocking antibody.

The combination is specifically indicated for:

• the treatment of adult patients with unresectable hepatocellular carcinoma
• use in combination with platinum-based chemotherapy for the treatment of adult patients with metastatic NSCLC with no sensitizing epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) genomic tumor aberrations

The combination of Imjudo/Imfinzi is supplied as an intravenous infusion administered over 60 minutes after dilution. Scroll down for specific dosing recommendations for each indication.

Mechanism of Action

Imjudo (tremelimumab) is a human monoclonal antibody that targets the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Imjudo blocks the activity of CTLA-4, contributing to T-cell activation, priming the immune response to cancer and fostering cancer cell death.

Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumor’s immune-evading tactics and releasing the inhibition of immune responses.

Side Effects

Adverse reactions may include, but are not limited to, the following:

• rash
• diarrhea
• fatigue
• pruritus
• musculoskeletal pain
• abdominal pain
• Laboratory abnormalities (≥ 40%) including:  AST increased, ALT increased, hemoglobin decreased, sodium decreased, bilirubin increased, alkaline phosphatase increased, and lymphocytes decreased

Indication 1 - unresectable hepatocellular carcinoma

approved October of 2022

Dosing/Administration

The recommended dose is based on weight:

• Weight 30 kg and more: Imjudo 300 mg as a single dose in combination with durvalumab 1,500 mg at Cycle 1/Day 1, followed by durvalumab as a single agent every 4 weeks
• Weight less than 30 kg: Imjudo 4 mg/kg as a single dose in combination with durvalumab 20 mg/kg at Cycle 1/Day 1, followed by durvalumab as a single agent every 4 week

Clinical Trial Results

The FDA approval Imjudo (tremelimumab) plus Imfinzi (durvalumab) was based on results from the phase 3 HIMALAYA trial. Patients treated with the combination of Imjudo and Imfinzi experienced a 22% reduction in the risk of death versus Bayer's Nexavar (sorafenib), a standard-of-care multi-kinase inhibitor. Approximately 31% of patients treated with the combination were still alive after three years, with 20% of patients treated with sorafenib still alive at the same duration of follow-up.

Indication 2 -  Stage IV (metastatic) NSCLC

approved November of 2022

Dosing/Administration

The recommended dose is based on weight:

Weight ≥ 30 kg: Imfinzi 1,500 mg every 3 weeks in combination with Imjudo (tremelimumab) 75 mg and platinum-based chemotherapy for 4 cycles, and then administer Imfinzi 1,500 mg every 4 weeks as a single agent with histology-based pemetrexed maintenance therapy every 4 weeks, and a fifth dose of Imjudo 75 mg in combination with Imfinzi dose 6 at week 16 

Weight < 30 kg: 20 mg/kg every 3 weeks in combination with Imjudo1 mg/kg and platinum-based chemotherapy, and then administer Imfinzi 20 mg/kg every 4 weeks as a single agent with histology-based pemetrexed therapy every 4 weeks, and a fifth dose of Imjudo 1 mg/kg in combination with Imfinzi dose 6 at week 1.

Clinical Trial Results

The approval was based on the results from the POSEIDON phase 3 trial. Patients treated with a limited course of five cycles of the anti-CTLA-4 antibody Imjudo added to Imfinzi plus four cycles of platinum-based chemotherapy experienced a 23% reduction in the risk of death versus a range of chemotherapy options. An estimated 33% of patients were alive at two years versus 22% for chemotherapy. This treatment combination also reduced the risk of disease progression or death by 28% compared to chemotherapy alone.