Olema Oncology announces interim results from Phase 1b/2 study of palazestrant

Olema Pharmaceuticals announced interim results from an ongoing Phase 1b/2 clinical study of palazestrant in combination with CDK4/6 inhibitor ribociclib, a Poster Spotlight Session on interim Phase 2 clinical data of palazestrant in combination with palbociclib, and a trials-in-progress poster for the OPERA-01 monotherapy Phase 3 pivotal trial at the San Antonio Breast Cancer Symposium at the Henry B. Gonzalez Convention Center in San Antonio, Texas. This disclosure was originally planned for December 7, 2023. However, on December 5, 2023, the 2023 San Antonio Breast Cancer Symposium published the posters ahead of schedule. These full data are scheduled to be presented on December 7, 2023, and copy of the posters are available now on Olema’s website under the Science section. Palazestrant Phase 1b/2 Study in Combination with Ribociclib: A poster titled “A Phase 1b/2 study of palazestrant in combination with ribociclib in patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative, advanced and/or metastatic breast cancer” will be presented at SABCS. A more recent data cut, as of November 1, 2023, highlights the following: Across 19 patients who had completed at least one cycle of treatment as of the data cutoff date, the combination of up to 120 mg of palazestrant with 600 mg of ribociclib daily was well tolerated, with no safety signals or enhancement of toxicity and an overall safety profile remains consistent with the expected safety profile of ribociclib plus an endocrine therapy. Palazestrant did not affect ribociclib drug exposure in patients, and ribociclib had no clinically meaningful effect on palazestrant drug exposure. There were no dose-limiting toxicities, the maximum tolerated dose was not reached, and the majority of treatment-emergent adverse events were grade 1 or 2, with no grade 4 events observed. Neutropenia was reversible in all patients, and the timing was generally consistent with ribociclib-related neutropenia. Findings from this study support the continued use of palazestrant at the recommended Phase 2 dose of 120 mg in combination with 600mg of ribociclib, and enrollment in the dose-expansion portion of the study is ongoing. Palazestrant Phase 1b/2 Study in Combination with Palbociclib: A poster titled “A Phase 1b/2 study of palazestrant, an oral complete estrogen receptor antagonist and selective ER degrader, with palbociclib in ER-positive, HER2-negative, advanced or metastatic breast cancer patients”, will be presented in a Poster Spotlight Session by Prof. Arlene Chan, FRACP, MMed, Breast Cancer Research Centre-WA, Curtin University, Breast Clinical Trials Unit, Hollywood Private Hospital, Nedlands, Australia. The presentation will highlight that: Across 46 patients as of the cutoff date of September 15, 2023, the combination of palazestrant with palbociclib daily was well tolerated, with an overall safety profile consistent with the expected safety profile of palbociclib plus an endocrine therapy. There was no observed drug-drug interaction between palazestrant and palbociclib, and there was no induced metabolism or increase in exposure of either palbociclib or palazestrant when administered in combination. Most treatment-emergent adverse events were grade 1 or 2. Neutropenia incidence was similar to the PALOMA-3 study; it was reversible in all patients and the timing was generally consistent with the palbociclib-related neutropenia. Tumor responses and prolonged disease stabilization were observed in this patient group, including in those previously exposed to CDK4/6 inhibitors, in both ESR1 mutant and ESR1 wild-type tumors. Partial responses were observed in seven patients, with two confirmed partial responses and five unconfirmed partial responses. The clinical benefit rate was 46% in all patients and 60% in patients with an ESR1 mutation at baseline. In patients naive to prior CDK4/6 inhibitor treatment, the CBR was 71%. 53% of patients had any reduction in target lesion size. Twenty-two patients remain on treatment, and efficacy data are still maturing. Findings from this study are consistent with previously reported data and support the ongoing clinical development of palazestrant in combination with CDK4/6 inhibitors for the treatment of ER+/HER2- metastatic breast cancer.