CHMP Recommends EU Approval for Durvalumab in Limited-Stage SCLC

Support for the recommendation is based on phase 3 ADRIATIC trial results showing a 27% reduction in the risk of death with durvalumab vs placebo.

The Committee for Medicinal Products for Human Use (CHMP) has recommended durvalumab (Imfinzi) for approval in the EU as a monotherapy to treat adult patients with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following chemoradiation therapy (CRT), according to a news release from the drug’s developer, AstraZeneca.¹

Support from for the recommendation follows results from the phase 3 ADRIATIC trial (NCT03703297) published in The New England Journal of Medicine.²Of note, durvalumab showed a 27% reduction in the risk of death vs placebo. Moreover, durvalumab monotherapy elicited a median overall survival (OS) of 55.9 months (95% CI, 37.3-not reached [NR]) vs 33.4 months (95% CI, 25.5-39.9) with placebo (stratified HR, 0.73; 95% CI, 0.57-0.93; P = .0104).

Additional data revealed a progression-free survival (PFS) benefit with durvalumab, with a median PFS of 16.6 months (95% CI, 10.2-28.2) vs 9.2 months (95% CI, 7.4-12.9) with placebo (stratified HR, 0.76; 95% CI, 0.61-0.95; P = .0161).

OS and PFS benefit with durvalumab was observed across all cohorts, with particular OS benefit observed in those with less than 14 days from concurrent CRT to randomization (HR, 0.47; 95% CI, 0.24-0.91), those with stable disease (HR, 0.54; 95% CI, 0.25-1.13), and those with a World Health Organization (WHO) performance status of 0 (HR, 0.55; 95% CI, 0.38-0.79). Furthermore, particular PFS benefit was observed in those with less than 14 days from concurrent CRT to randomization (HR, 0.45; 95% CI, 0.24-0.83), those who underwent previous carboplatin/etoposide (HR, 0.61, 0.41-0.90), and those with a WHO performance status of 0 (HR, 0.64; 95% CI, 0.46-0.90).

“ADRIATIC was the first phase 3 trial in decades to demonstrate a survival benefit in limited-stage [SCLC], reducing the risk of death by 27% in patients treated with durvalumab vs placebo,” Suresh Senan, PhD, professor of Clinical Experimental Radiotherapy at the Amsterdam University Medical Centers in the Netherlands and principal investigator of the study, said in the news release on the recommendation.¹ “Today’s positive recommendation from the CHMP means that our patients in Europe are one step closer to gaining access to this practice-changing treatment regimen.”

The phase 3 trial enrolled and randomly assigned 730 patients with histologically confirmed or cytologically documented LS-SCLC without progressive disease after receiving concurrent CRT 1:1:1 to receive either durvalumab monotherapy (n = 264), durvalumab plus tremelimumab (Imjudo; n = 200), or placebo (n = 266). Findings from the durvalumab monotherapy and placebo arms were included in the interim analysis.

Patients in the durvalumab group were given 1500 mg of durvalumab plus durvalumab-matched placebo every 4 weeks.³ Those in the placebo group received durvalumab-matched placebo plus tremelimumab-matched placebo every 4 weeks for 4 doses followed by durvalumab-matched placebo every 4 weeks.

Patients in the investigational and placebo arms, respectively, had a median age of 62 years (range, 28-84) and 62 years (28-79), were primarily male (67.4% vs 70.7%), and were mostly White (49.2% vs 51.5%) or Asian (49.6% vs 45.5%). A total of 91.3% and 90.2% of patients were current or former smokers, 87.5% and 87.2% had tumor-node-metastasis stage III disease at diagnosis, and 72.3% and 75.2% had a partial response as the best previous response, respectively.

The coprimary endpoints were OS and PFS. Secondary end points included objective response rate, time to death or distant metastasis, health-related quality of life, pharmacokinetics, and safety.³

Any-grade adverse events (AEs) were observed in 94.3% of the durvalumab arm and 88.3% of the placebo arm. Grade 3 or higher AEs occurred in 24.4% and 24.2% of the respective arms, and serious AEs were reported in 29.8% and 24.2%. AEs leading to dose interruption, dose discontinuation, or death were reported in 34.7%, 16.4%, and 2.7% of the investigational arm and 28.7%, 10.6%, and 1.9% of the placebo arm.

The FDA previously approved durvalumab for patients with LS-SCLC in December 2024 based on data from the ADRIATIC trial.⁴

References

1. Imfinzi recommended for approval in the EU by CHMP as first and only immunotherapy for limited-stage small cell lung cancer. News release. AstraZeneca. February 3, 2025. Accessed February 4, 2025. https://tinyurl.com/4r6bcjvx
2. Cheng Y, Spigel DR, Cho BC, et al. Durvalumab after chemoradiotherapy in limited-stage small-cell lung cancer. N Engl J Med. 2024;391(14):1313-1327. doi:10.1056/NEJMoa2404873
3. Study of durvalumab + tremelimumab, durvalumab, and placebo in limited stage small-cell lung cancer in patients who have not progressed following concurrent chemoradiation therapy (ADRIATIC). ClinicalTrials.gov. Updated November 6, 2024. Accessed February 4, 2025. https://tinyurl.com/4drr99ws
4. FDA approves durvalumab for limited-stage small cell lung cancer. News release. FDA. December 4, 2024. Accessed February 4, 2025. https://shorturl.at/0eID1