FDA Approves Tremelimumab Plus Durvalumab With Chemotherapy for Metastatic Non-Small Cell Lung Cancer


Tremelimumab-actl (Imjudo) plus durvalumab (Imfinzi) and platinum-based chemotherapy approved for the treatment of adults with metastatic non–small cell lung cancer without sensitizing EGFR mutation or ALK aberrations.

The FDA has approved tremelimumab-actl (Imjudo) plus durvalumab (Imfinzi) and platinum-based chemotherapy for the treatment of adults with metastatic non–small cell lung cancer (NSCLC) without sensitizing EGFR mutation or ALK aberrations.1-4 The approval was based on data from the randomized, open-label, multi-center, global, phase 3 POSEIDON trial (NCT03164616).

“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,” 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 trial, said in a press release.4 “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.”

Patient eligibility for POSEIDON required an ECOG performance status of 0 or 1 and patients could not have been previously treated with chemotherapy or another systemic treatment for metastatic disease. Other criteria for exclusion included active and/or untreated brain metastases, history of active primary immunodeficiency, autoimmune disorders, or use of systemic immunosuppressants within 2 weeks prior to the first dose of tremelimumab-actl plus durvalumab.

Patients were randomized to receive either tremelimumab plus durvalumab and platinum-based chemotherapy, durvalumab plus platinum-based chemotherapy, or platinum-based chemotherapy. Efficacy analysis was based on a comparison among the 675 patients enrolled to the tremelimumab plus durvalumab and platinum-based chemotherapy arm (n = 338) and the platinum-based chemotherapy alone arm (n = 337).

Tremelimumab was administered at 75 mg or 1 mg/kg in patients <30 kg plus durvalumab at 1500 mg and platinum-based chemotherapy every 3 weeks for 4 cycles, followed by durvalumab monotherapy at 1500 mg every 4 weeks. At week 16, a fifth dose of tremelimumab at 75 mg was administered combined with the sixth dose of durvalumab.

In the other evaluation arm, patients received platinum-based chemotherapy every 3 weeks as monotherapy for 4 cycles. Patients could then be administered an additional 2 cycles for a total of 6 cycles after randomization per investigator discretion.

Treatment continued until progressive disease or intolerable toxicity. Patients were stratified based on PD-L1 expression on tumor cells (≥50% vs <50%), disease stage (stage IVA vs stage IVB), and histology (nonsquamous vs squamous).

POSEIDON’s primary outcome measures included overall survival (OS) and progression-free survival (PFS) determined by blinded independent central review in accordance with RECIST v1.1 criteria. Additional outcome measures included overall response rate (ORR) and duration of response (DoR).

Patients in the 2 comparison arms had a median age of 63 years ranging from 27 to 87 years, with 46% aged 65 years or older; 77% were male, 57% White, and 79% were former or current smokers.

The tremelimumab, durvalumab, and chemotherapy combination was found to significantly improve OS vs chemotherapy alone, at 14 months (95% CI, 11.7-16.1) compared with 11.7 months (95% CI, 10.5-13.1), respectively, which represents a 23% decline in the risk of death (HR, 0.77; 95% CI, 0.65-0.92; 2-sided = .00304).

Patients in the tremelimumab plus durvalumab and platinum-based chemotherapy cohort were found to have improved PFS vs the chemotherapy alone cohort, at 6.2 months (95% CI, 5.0-6.5) and 4.8 months (95% CI, 4.6-5.8), respectively, which translates to a 28% decrease in the risk of disease progression or death (HR, 0.72; 95% CI, 0.60-0.86; 2-sided P = .00031).

Tremelimumab plus durvalumab and platinum-based chemotherapy produced an ORR of 39% (95% CI, 34%-44%) compared with 24% (95% CI, 20%-29%) in the platinum-based chemotherapy alone cohort. Median DoR in the tremelimumab plus durvalumab and platinum-based chemotherapy was 9.5 months (95% CI, 7.2–not reached) compared with 5.1 months (95% CI, 4.4-6.0) in chemotherapy alone cohort.

The most commonly reported toxicities in at least 20% of patients were nausea, fatigue, musculoskeletal pain, decreased appetite, rash, and diarrhea. Grade 3 or 4 laboratory abnormalities occurring in at least 10% of patients were neutropenia, anemia, leukopenia, lymphocytopenia, lipase increased, hyponatremia and thrombocytopenia.

Serious toxicities were observed in 44% of patients administered the combination treatment, and included pneumonia (11%), anemia (5%), diarrhea (2.4%), thrombocytopenia (2.4%), pyrexia (2.4%), and febrile neutropenia (2.1%).

Additionally, 4.2% of patients had fatal adverse reactions, including hepatitis, nephritis, myocarditis, pancreatitis (all in the same patient); death (n = 2); sepsis (n = 2); pneumonitis (n = 2); acute kidney injury (n = 2); febrile neutropenia (n = 1); chronic obstructive pulmonary disease (n = 1); dyspnea (n = 1); sudden death (n = 1); and ischemic stroke (n = 1).

“This approval underscores the importance of delivering novel treatment combinations that extend survival in metastatic non-small cell lung cancer, a complex setting where many patients still face a dismal prognosis,” said Dave Fredrickson, executive vice president, Oncology Business Unit, AstraZeneca, in a press release.4 “This marks the second indication for Imjudo added to Imfinzi in just a few weeks following its approval in unresectable liver cancer, reinforcing the benefits of this new medicine and our commitment to improving patient outcomes in cancer settings with continued unmet need.”


  1. FDA approves tremelimumab in combination with durvalumab and platinum-based chemotherapy for metastatic non-small cell lung cancer. News release. FDA. November 10, 2022. Accessed November 10, 2022. http://bit.ly/3Ej7yIx
  2. Imjudo (tremelimumab-actl). Prescribing information; AstraZeneca Pharmaceuticals; 2022. Accessed November 10, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761270s000lbl.pdf
  3. Imfinzi (durvalumab). Prescribing information; AstraZeneca Pharmaceuticals; 2022. Accessed November 10, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761069s033lbl.pdf
  4. Imfinzi and Imjudo with chemotherapy approved in the US for patients with metastatic non-small cell lung cancer. AstraZeneca. News release. November 11, 2022. https://www.astrazeneca.com/media-centre/press-releases/2022/imfinzi-and-imjudo-approved-in-us-for-lung-cancer.html
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