A biomarker-stratified trial design was feasible, and early efficacy signals were observed with ceralasertib plus durvalumab among patients with advanced non-small cell lung cancer (NSCLC), according to preliminary data from the phase 2 HUDSON study presented at the 2020 World Conference on Lung Cancer in Singapore.1
The phase 2 HUDSON study (NCT03334617) included 2 cohorts of patients with locally advanced or metastatic NSCLC who were previously treated with platinum-based chemotherapy and whose disease progressed on prior anti-PD-1/PD-L1 therapy.
Cohort A included 85 patients who were assigned biomarker-selected targeted therapy plus durvalumab. This biomarker-matched cohort included individuals with alterations in homologous recombination repair (HRR) genes, STK11, ATM, CD73, or HER2, as well as patients with HER2 expression.
Cohort B enrolled 177 patients who received targeted therapy plus durvalumab regardless of their biomarker status. These patients were stratified by primary or acquired resistance to prior immunotherapy.
The primary end point was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate, and safety.
Across all 3 cohorts, the highest ORR rates were observed with ceralasertib plus durvalumab at 11.1% (cohort A), 10.5% (cohort B, primary resistance group), and 8.3% (cohort B, acquired resistance group). In cohort A, the ORR was 9.5% with olaparib plus durvalumab in patients with an HRR gene mutation and 4.8% among patients with a STK11 mutation. There were no responses to oleclumab plus durvalumab among patients with a 73H mutation.
In cohort B, patients with primary resistance to immunotherapy did not respond to therapies other than ceralasertib plus durvalumab. Among patients in cohort B with acquired resistance to immunotherapy, the ORR was 4.3% with olaparib/durvalumab and 4.2% with oleclumab/durvalumab. There were no responses to danvatirsen/durvalumab.
The median PFS was highest among the patients who were molecularly selected based on an ATM mutation (7.43 months), followed by patients in cohort B’s primary resistance group who received ceralasertib/durvalumab (4.24 months), and patients in the acquired resistance group (4.96 months).
The median OS was also congested with ceralasertib plus durvalumab, with a median of 15.80 months in cohort A, and 11.60 and 17.38 months in cohort B’s primary and acquired resistance groups, respectively.
The study authors concluded that “preliminary efficacy signals were observed in patients who received ceralasertib plus durvalumab,” which was “potentially more pronounced in ATM-selected patients (ATR-low or -mutated).”
Disclosures: Benjamin Besse, MD, disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the original study. This research was supported by AstraZeneca.
Besse B, Awad M, Forde P, et al. An open-label, multi-drug, biomarker-directed, phase II platform study in patients with non-small cell lung cancer, who progressed on an anti-PD(L)-1 therapy. Presented at: 2020 World Conference on Lung Cancer Singapore; January 28-31, 2020. Abstract OA07.08.