Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2023

A phase 1b/2 study of OP-1250, an oral complete estrogen receptor (ER) antagonist (CERAN) and selective ER degrader (SERD) with palbociclib in patients (pts) with advanced or metastatic ER-positive, HER2-negative breast cancer (MBC)  (#190)

Daphne Day 1 , Arlene Chan 2 , Phuong Dinh 3 , Michael Slancar 4 , Vinod Ganju 5 , Nicole McCarthy 6 , Janine Lombard 7 , Demiana Faltaos 8 , Mark Shilkrut 9 , Rosalind Wilson 10 , Caitlin Murphy 11
  1. Monash Health, Monash University, Clayton, VIC, Australia
  2. Breast Cancer Research Centre, Curtin University, Breast Clinical Trials Unit, Hollywood Private Hospital, Nedlands, WA, Australia
  3. Crown Princess Mary Cancer Care Centre, Westmead, NSW, Australia
  4. ICON Cancer Centre, Southport, QLD, Australia
  5. Pininsula & South Eastern Haematology and Oncology Group, Frankston, VIC, Australia
  6. ICON Cancer Centre Wesley, Auchenflower, QLD, Australia
  7. Calvary Mater Newcastle, Waratah, NSW, Australia
  8. Clinical Pharmacology, Olema Oncology, San Francisco, California, United States
  9. Clinical Development, Olema Oncology, San Francisco, California, United States
  10. Clinical Science, Olema Oncology, San Francisco, California, United States
  11. Cancer Services Trial Unit, University Hospital Geelong, Barwon Health, Geelong, VIC, Australia

Background: OP-1250 is small molecule CERAN/SERD that binds to and completely blocks transcriptional activity of wild-type and mutant ER. OP-1250 was well tolerated in a phase 1/2 monotherapy study (OP-1250-001), and the recommended phase 2 dose is 120 mg once a day (qd). OP-1250 with palbociclib showed synergistic activity in preclinical models. Here we report updates of pharmacokinetics (PK), drug-drug interactions (DDI), safety and efficacy from a study of OP-1250 with palbociclib (OP-1250-002).  

Methods: Pts with advanced or MBC with progression on or after ≤1 line of endocrine therapy (prior CDK4/6 inhibitors and chemotherapy were allowed) were enrolled into sequential cohorts to receive escalating doses of OP-1250 PO qd with palbociclib 125 mg PO qd for 21 of 28 days, using a 3+3 design, followed by dose expansion.   

Results: As of January 23, 2023, 20 pts have been treated with palbociclib and OP-1250 doses of 30/60/90/120 mg (n=3/3/3/11). Fourteen received prior CDK4/6 inhibitor; 11 received prior palbociclib. No DLTs occurred. The most common (≥4 pts) treatment emergent adverse events (AEs) were neutropenia, nausea, vomiting, anemia, gastroesophageal reflux, constipation, and thrombocytopenia (all were Grade 1-2, except neutropenia). Grade 3 neutropenia occurred in 11 pts (55%). No Grade 4 AEs occurred. The exposure of OP-1250 (n=18) was consistent with the monotherapy study. Palbociclib exposure at steady state was comparable to published monotherapy data when combined with OP-1250 at all dose levels tested. Anti-tumor activity has been observed including partial responses.   

Conclusions: OP-1250 did not affect palbociclib PK and no DDIs have been observed with this combination. OP-1250 and palbociclib combination was well tolerated, safety was consistent with individual profiles of each drug as a monotherapy. Tumor responses were observed in this heavily pretreated population. Expanding on our previous report (SABCS 2022), these data provide rationale to continue exploring OP-1250 with the approved dose of palbociclib.  (NCT0526610)