The Food and Drug Administration (FDA) has approved Imjudo (tremelimumab-actl) in combination with Imfinzi (durvalumab) and platinum-based chemotherapy for the treatment of adults with metastatic non-small cell lung cancer (NSCLC) with no sensitizing epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) genomic tumor aberrations.
Imjudo is a human monoclonal antibody that targets the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). The approval was based on data from the randomized, multicenter, active-controlled, open-label phase 3 POSEIDON study (ClinicalTrials.gov Identifier: NCT03164616), which evaluated the efficacy and safety of tremelimumab plus durvalumab, a programmed death-ligand 1 (PD-L1) blocking antibody, and platinum-based chemotherapy in 675 patients with metastatic NSCLC who had not received prior systemic therapy.
Patients were randomly assigned 1:1:1 to receive 1 of the 3 treatment arms: (1) tremelimumab plus durvalumab and platinum-based chemotherapy; (2) durvalumab plus platinum-based chemotherapy; or (3) platinum-based chemotherapy. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Key secondary endpoints included overall response rate (ORR) and duration of response (DoR).
Results showed that treatment with tremelimumab plus durvalumab and platinum-based chemotherapy demonstrated a statistically significant and clinically meaningful improvement in OS compared with platinum-based chemotherapy (hazard ratio [HR], 0.77 [95% CI, 0.65-0.92]; 2-sided P =.00304). Median OS was 14 months and 11.7 months for treatment arms 1 and 3, respectively.
Additionally, a statistically significant and clinically meaningful improvement in PFS was observed with tremelimumab plus durvalumab and platinum-based chemotherapy compared with platinum-based chemotherapy (HR, 0.72 [95% CI, 0.60-0.86]; 2-sided P =.00031). Median PFS was 6.2 months and 4.8 months for treatment arms 1 and 3, respectively.
The ORR was 39% (95% CI, 34-44) in the combination arm and 24% (95% CI, 20-29) in the chemotherapy arm. Median DoR was 9.5 months (95% CI, 7.2-not reached) and 5.1 months (95% CI, 4.4-6.0) for treatment arms 1 and 3, respectively.
The most common adverse reactions reported were nausea, fatigue, decreased appetite, musculoskeletal pain, rash, and diarrhea. The most common grade 3 or 4 laboratory abnormalities were neutropenia, anemia, leukopenia, lymphocytopenia, increased lipase, hyponatremia, and thrombocytopenia.
“Metastatic non-small cell lung cancer remains a significant treatment challenge because many patients’ tumors do not respond well to standard therapies, including checkpoint inhibitors,” said Melissa Johnson, MD, Director of Lung Cancer Research, Sarah Cannon Research Institute at Tennessee Oncology in Nashville, Tennessee, and a lead investigator in the POSEIDON phase 3 trial. “The approval of this dual immunotherapy regimen with chemotherapy introduces a new, generally well-tolerated treatment option for patients with this devastating disease and gives them the chance to benefit from the long-term survival advantage seen with CTLA-4 inhibition.”
Recently announced results from the POSEIDON trial showed the combination improved overall survival by 25% when compared with chemotherapy alone (HR, 0.75; 95% CI, 0.63-0.88). An estimated 25% of patients treated with tremelimumab plus durvalumab and platinum-based chemotherapy were alive at 3 years vs 13.6% of those treated with chemotherapy alone.
Imjudo is also indicated in combination with Imfinzi for the treatment of adults with unresectable hepatocellular carcinoma.
- FDA approves tremelimumab in combination with durvalumab and platinum-based chemotherapy for metastatic non-small cell lung cancer. News release. US Food and Drug Administration. Accessed November 10, 2022. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tremelimumab-combination-durvalumab-and-platinum-based-chemotherapy-metastatic-non
- Imfinzi and Imjudo with chemotherapy approved in the US for patients with metastatic non-small cell lung cancer. News release. November 11, 2022. https://www.businesswire.com/news/home/20221111005248/en/IMFINZI-and-IMJUDO-with-chemotherapy-approved-in-the-US-for-patients-with-metastatic-non-small-cell-lung-cancer
- Imjudo. Package insert. AstraZeneca; 2022. Accessed November 10, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761270s000lbl.pdf