Imfinzi and Imjudo with Chemotherapy Approved in the US for Patients with Metastatic NSCLC

On November 10, 2022, the FDA approved tremelimumab (Imjudo, AstraZeneca) plus durvalumab (Imfinzi, AstraZeneca) and platinum-based chemotherapy for adult patients with Stage IV non–small cell lung cancer (NSCLC) without sensitizing EGFR mutation or ALK genomic tumor aberrations.

The efficacy was evaluated in the carried out trial named POSEIDON, a randomized (1:1:1), multicenter, active-controlled, open-label study in which patients (who had not previously received systemic treatment) with metastatic NSCLC participated.

Study participants were randomly assigned to one of the following three treatment arms:
1. tremelimumab (Imjudo), durvalumab (Imfinzi), and platinum-based chemo for four cycles, followed by durvalumab (Imfinzi) and maintenance chemo every four weeks. Patients were given fifth tremelimumab dose at week 16;
2. durvalumab (Imfinzi) plus platinum-based chemo for four cycles followed by durvalumab (Imfinzi) and maintenance chemo; or
3. platinum-based chemo for six cycles followed by maintenance chemo.

Treatment was continued until the disease was progressive or unacceptable toxicity occurred. This approval depends upon a comparison of treatment arm one and three (675 patients).

The major efficacy outcome measures were PFS assessed using blinded independent central review as per RECIST v1.1. and OS (overall survival). The drug Tremelimumab in combination with durvalumab and platinum-based chemo showed a statistically significant and clinically meaningful enhancement in overall survival compared to platinum-based chemotherapy.

Overall response rate (ORR) was 39 percent (95 percent CI: 34, 44) in and 24 percent (95 percent CI: 20, 29) in the treatment arm 1 & 3, respectively. Median duration of response was 9.5 months (95 percent CI: 7.2, not reached) and 5.1 months (95 percent CI: 4.4, 6.0) in a couple of treatment arms.

The most commonly reported side effects (≥ 20%) are decreased appetite, nausea, fatigue, rash, musculoskeletal pain, and diarrhea.
Reported laboratory abnormalities (grade 3/4) are lipase increased, lymphocytopenia, hyponatremia, neutropenia, leukopenia, anemia, and thrombocytopenia.

The proposed dose of tremelimumab for those weighing 30 kg or beyond is 75 mg IV every three weeks (21 days) with medicine durvalumab 1500 mg IV and platinum-based chemo for 4 cycles, then medicine durvalumab 1500 mg with maintenance chemotherapy every 4 weeks. A fifth dose of tremelimumab (75 mg) should be administered at week 16’th.

With the above schedule, for patients weighing 30 kg or less, the proposed tremelimumab dose is 1 mg per kg and the durvalumab dose is 20 mg per kg.

Stats:
In the United States, lung cancer is the second most commonly diagnosed cancer, with over 236,000 patients expected to be diagnosed in 2022. For patients with stage IV non-small cell lung cancer (NSCLC), prognosis is particularly low, as estimated only 8% will live beyond 5 (60 months) years after diagnosis.

Metastatic (Stage IV) NSCLC:
Worldwide, lung cancer is the second most common form of cancer, with more than 2 Million patients diagnosed in the year of 2020. Cancer of the lung is broadly split into non-small cell lung cancer (NSCLC) and squamous cell lung cancer (SCLC), with 80 to 85% classified as non-small cell lung cancer (NSCLC). Within NSCLC, patients are classified as squamous cell lung cancer, representing 25 to 30% of patients, or non-squamous, in approximately 70 to 75% of patients.

Reference:
https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tremelimumab-combination-durvalumab-and-platinum-based-chemotherapy-metastatic-non