Sareum (SAR) has noted the presentation by its partner Sierra Oncology of preclinical data showing “profound synergy” for the triple combination of the CHK1 inhibitor SRA737 in combination with low-dose gemcitabine (LDG) and anti-PD-L1 immunotherapy in a mouse model of small cell lung cancer (SCLC). The data were reported in a late-breaking oral presentation at the American Association of Cancer Research (AACR) Annual Meeting. Sareum originated SRA737 and holds a 27.5% economic interest in the licensing deal covering the drug.
In the study presented, the three agent combination showed durable tumour regression in 10/10 animals at the end of the 21-day treatment period with 8/10 showing sustained complete response after a further 39 days without further treatment. The abstract notes that anti-PD-L1 immunotherapy and LDG demonstrated minimal effects on tumour growth as single agents and only a modest effect as a combination, while a moderate to strong anti-tumour activity with SRA737 monotherapy was observed that correlated with dose intensity.
SCLC, which accounts for c15% of all lung cancer cases, is one of four subsidiary indications being pursued by Sierra in the ongoing study of SRA737 in combination with LDG. The latest preclincial findings suggest that the combination of anti-PD-L1 immunotherapy with the SRA737+LDG provide a strong rationale for combining these agents to enhance clinical response rates. Last month, Roche received US approval for Tecentriq (atezolizumab), its PD-L1 antibody, for use in combination with carboplatin/etoposide (chemotherapy) for the initial (first-line) treatment of extensive-stage SCLC and this combination is already being treated as the new standard of care. This approval was based on data from the Phase III IMpower133 study, which showed that Tecentriq in combination with chemotherapy conferred a 30% improvemnent in median overall survival (12.3 vs. 10.3 months; hazard ratio =0.70, p=0.0069).
Sierra’s main focus for SRA737 is in high-grade serous ovarian cancer (HGSOC). Sierra aims to present preliminary clinical data on SRA737 at the high profile American Society for Clnical Oncology (ASCO) meeting in June. Abstract headlines for ASCO are disclosed in mid-April, with the texts revealed on May 15. Assuming an abstract(s) is accepted, data that could be submitted are likely to include safety, pharmacokinetics, and dosing with possibly some preliminary evidence of activity.
Meanwhile, Lilly – the key competitor that has a CHK1 inhibitor in development – reported results from a small clinical trial of its agent prexasertib at AACR. The abstract states that three of 21 with BRCA1-mutant patients achieved partial responses, two of whom had progressed on a prior PARP inhibitor (a drug type used in first line maintennance of HGSOC). A scientific journal publication in February described results a study of prexasertib in 28 heavily pre-treated women with HGSOC, most of which [79%] had platinum resistant or refractory disease. Of the 24 patients evaluable for response, eight (33%) had a partial results and five (26%) had stable disease. All these patients were BRACA wild-type, the grouip that responds least well to PARP inhibitors.