Riboxiclib/Calilon and Palazestrant combination shows preliminary activity in ER+/her 2- breast cancer

Based on published data from the Phase 1b OP-1250-003 study (NCT05508906), Riboxil/Calilon(Ribociclib) in combination with palazestrant (OP-1250) showed early encouraging activity in patients with advanced estrogen receptor (ER)-positive, HER2-negative breast cancer.

Among patients who received 120 mg of palazterant, median progression-free survival (PFS) was 15.5 months (95% CI, 9.0-not evaluable [NE]) for all patients (n=56) and 12.2 months, 95% CI, 7.2-NE for patients who had previously received a CDK4/6 inhibitor plus endocrine therapy (n=40). Additionally, median PFS was 9.2 months (95% CI, 2.1-NE) for patients with ESR1 wild-type disease and prior CDK4/6 inhibitors (n=24) and 13.8 months (95% CI, 7.3-NE) for patients with ESRI-mutated disease and prior CDK4/6 inhibitors (n=14). Among patients treated with 90 mg of palazterant, median follow-up was 10.8 months and median PFS was not reached.

The data showed that the overall population objective response rate (ORR) was 34% (n=44), including 2 confirmed complete responses and 13 confirmed partial responses. Additionally, the ORR was 42% (5 of 12) in the 90 mg arm, 31% (10 of 32) in the 120 mg arm, and 26% (6 of 23) in patients who received 120 mg of palazterant and a prior CDK4/6 inhibitor.

At the time of analysis,42% (n=72) of patients were still receiving study treatment. The 120 mg group had the longest treatment duration at 103 weeks; this patient's treatment is still ongoing. Palazterant was well tolerated when used in combination with 600 mg of reboxil. Safety was consistent with the known safety profile of each drug; palazterant and reboxiclib did not exhibit any drug-driven interactions. [ER-positive, HER2-negative] First-line treatment of advanced breast cancer.

The OP-1250-003 trial consists of a dose escalation portion and a dose expansion phase. In the dose-escalation phase, patients were assigned to receive 120 mg (n = 3), 60 mg (n = 4), or 30 mg (n = 6) of palazterant plus 600 mg of reboxil. As part of the dose-expansion portion, patients received 90 mg (n = 16) or 120 mg (n = 53) of palazterant plus ripociclib.

The trial's primary endpoints include dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), recommended phase 2 dose, pharmacokinetics, and incidence and severity of adverse effects (AEs). Secondary endpoints include ORR, clinical benefit rate, duration of response, time to progression, and PFS.

Patients 18 years of age or older with histologically or cytologically confirmed advanced or metastatic breast cancer; ER-positive, HER2-negative disease based on archived tumor tissue samples; and patients with a life expectancy of at least 6 months are eligible to participate in the trial. 2 Additional eligibility criteria include ECOG performance status of 0 or 1 and no more than 1 prior chemotherapy regimen for locally advanced or metastatic disease.

Across the entire population, the median age was 61 years (range, 25-85 years), all patients were female (100%), and the majority were not premenopausal (17%). Additionally, the majority of the study population had an ECOG performance status of 0 (61%), measurable disease at baseline (68%), visceral disease (54%), 1 prior line of therapy for advanced disease (43%), 1 prior line of endocrine therapy for advanced disease (53%), and prior CDK4/6 inhibitor therapy (63%).

The data showed noDLT during the dose escalation portion of the trial; the MTD was not reached. Two patients required a dose reduction of Palazestrant due to a single episode of nausea and neutropenia. Researchers reduced the dose of both drugs in eight patients and only ribocytidine in 23 patients, most commonly due to neutropenia.

The most common adverse events of any grade in patients taking 120 mg and 90 mg of palazterant respectively were neutropenia, nausea, fatigue, leukopenia, and diarrhea. Grade 4 toxicities included neutropenia in 9% of the 120 mg cohort and 16% of the 90 mg cohort; other Grade 4 toxicities in the 120 mg cohort included leukopenia and lymphopenia.

Reference materials:https://www.cancernetwork.com/view/palazestrant-combo-shows-preliminary-activity-in-er-her2-breast-cancer