KEY TAKEAWAYS
- An interventional phase I/II trial aimed to assess the safety and efficacy of senaparib + temozolomide in relapsed ES-SCLC through Part 2 dose expansion.
- The primary endpoint was ORR.
- The study found that continuous senaparib + intermittent low-dose temozolomide showed early promise in relapsed ES-SCLC with manageable toxicity, warranting further investigation in HRR-mutant patients.
Extensive-stage small cell lung cancer (ES-SCLC) presents a therapeutic challenge, characterized by limited treatment options and a median overall survival (mOS) of approximately 6 months upon relapse.
M.H. Hong and his research team spearheaded a study that aimed to present findings from Part 2 (dose expansion) of an ongoing Phase Ib/II study (NCT04434482) assessing the combination of senaparib, a novel Poly (ADP-ribose) polymerase inhibitor, with temozolomide in relapsed ES-SCLC patients.
The study consisted of two parts: Part 1, completed with the recommended phase 2 dose (RP2D) determined as continuous senaparib 80 mg daily alongside temozolomide 20 mg daily (D1-21 of 28 days a cycle) (Bo Gao ASCO 2022). For Part 2, ES-SCLC patients experiencing disease progression after one course of first-line standard platinum-based therapy were enrolled, evaluating efficacy and safety using the RP2D determined by Simon 2-stage design.
Both platinum-sensitive (defined as disease-free interval between relapse and the last dose of platinum doublets exceeding 90 days) and platinum-resistant patients were eligible. The objective response rate (ORR) per RECIST v1.1 was the primary endpoint.
About 45 enrolled patients (75.6% male, 75.6% Asian, 95.5% ECOG score 0-1, 60.0% platinum-sensitive, 84.4% prior PD-1/PD-L1, 77.8% free of brain metastasis) underwent a median 6.0 months follow-up, with 9 of 42 evaluable patients showing reported partial responses, 6 subsequently confirmed.
The overall mOS stood at 13.1 months. Notably, 1 patient each from platinum-sensitive and -resistant groups with confirmed partial responses exhibited progression-free survivals(PFS) of 5.8 and 5.4 months, respectively; 1 achieved an OS of 13.1 months, and the other is still under follow-up beyond 14 months, 3 out of 7 patients with FANC family mutations reported confirmed partial responses. Overall, 44.4% of patients experienced at least one dose reduction, mainly due to hematological toxicity.
The most common treatment-emergent adverse events (TEAEs) deemed grade 3 or higher included neutropenia (35.6%), thrombocytopenia (31.1%), and anemia (33.3%), with no TEAE resulting in a fatal outcome.
The combination of continuous senaparib and intermittent low-dose temozolomide demonstrated the clinical survival benefit with manageable hematological toxicity in relapsed ES-SCLC, emphasizing the need for further investigation into the relationship with homogeneous recombination repair gene mutations. The research was sponsored by Impact Therapeutics, Inc.
Source: https://cattendee.abstractsonline.com/meeting/10925/presentation/1027
Clinical Trial: https://clinicaltrials.gov/study/NCT04434482
Hong MH, Gao B, Cheng Y., et al.(2023) “A Phase Ib/II Study of Senaparib in Combination with Low-dose Temozolomide: Updated Results in Relapsed ES-SCLC Patients.’’ Presented at the IASLC, 2023 World Conference on Lung Cancer, Singapore.
