Phase 2 Study Evaluates Maintenance Atezolizumab Plus Talazoparib in ES-SCLC

Maintenance atezolizumab plus talazoparib (AT) showed an improvement in progression-free survival (PFS) compared to maintenance atezolizumab alone (A) in patients with Schlafen 11 (SLFN₁₁)-positive extensive stage small cell lung cancer (ES-SCLC) after frontline chemoimmunotherapy.

The randomized, phase 2 study evaluated whether adding talazoparib to atezolizumab, a maintenance immune checkpoint inhibitor, after chemotherapy, would improve outcomes for patients with ES-SCLC.

Nagla Abdel Karim, MD, PhD, director of the Phase I Program at Inova Schar Cancer Institute in Virginia, and the principal investigator of the study, targeted a sample size of at least 84 eligible patients who were newly diagnosed with SLFN₁₁-expressing ES-SCLC.

“The primary objective was to compare progression-free survival (PFS) using a 1-sided 10% level stratified log-rank test,” according to the study. The secondary endpoints were toxicity, overall survival (OS), and objective response rate (ORR).

The investigators surpassed their target sample size and evaluated 106 patients between June 15, 2020, and December 15, 2022. Participants in the study were randomly assigned either maintenance A or maintenance AT after receiving frontline chemotherapy. Fifty-four participants received AT, and 52 received A.

The AT cohort demonstrated improvement in PFS compared to the A cohort (hazard ratio [HR], 0.66; 80% CI: 0.50-0.86; one-sided P=.019). The median PFS in each group was 2.9 months and 2.4 months, respectively. Neither cohort showed a difference in OS (HR, 0.98; 80% CI: 0.71-1.36; one-sided P=.47).

Treatment-related adverse events (TRAEs) were observed in both groups, with 17% of the AT cohort and 14% of the A cohort experiencing a non-hematologic TRAE greater than or equal to grade three. According to the study, hematological TRAEs greater than or equal to grade three “were more common in AT (50%) than in A (4%) (P<.001).”

The study results pointed to a marked improvement in PFS in patients with SLFN₁₁-positive ES-SCLC “that did not progress,” who were treated with maintenance AT following “initial chemoimmunotherapy.”

The researchers drew additional conclusions from the study, including an increase in hematologic toxicity, such as grade 3 anemia, in the AT group. The study also demonstrated “prospective biomarker-selection;” a result the investigators stated could pave the way “for future evaluation of novel therapies in molecularly defined SCLC populations.”

Source: Journal of Thoracic Oncology