NCT05810870

PIK3CA/PTEN-altered Advanced Breast Cancer Treated With MEN1611 Monotherapy or in Combination With Eribulin

Phase II Study for Patients With Advanced Triple Negative or Metaplastic HR-positive/HER2-negative, PIK3CA/PTEN-altered Breast Cancer Treated With Eribulin in Combination With MEN1611

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 14 (actual)
• Sponsor: MedSIR · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The multicenter, two-cohort, non-comparative, open-label, phase II clinical trial SABINA aims to analyze the safety and efficacy of MEN1611 in monotherapy and in combination with eribulin, a non-taxane chemotherapy agent, in Hormone Receptor (HR)-known/Human Epidermial Growth Factor Receptor 2 (HER2)-negative, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)/ Phosphatase and Tensin Homolog (PTEN)-altered, unresectable locally advanced or metastatic metaplastic breast carcinoma (MpBC) patients. A run-in phase for safety and tolerability of MEN1611 in combination with standard doses of eribulin will be conducted as an initial step of the cohort A. This first step aims at evaluating the dosing schedule of MEN1611, by analyzing the toxicity profile of the combined regimen. With the background of the first-in-human study (PA-001EU), the safe dose of MEN1611 has been established as 48 mg orally BID (two intakes of 3 capsules of 16 mg each, for a total daily dose of 96 mg MEN1611 free-base).

Detailed description

This is a multicenter, two-cohort, non-comparative, open-label, phase II clinical trial to assess: * the efficacy of MEN1611 in combination with eribulin as determined by the clinical benefit rate (CBR) in unresectable locally advanced or metastatic HR-known/HER2-negative, PIK3CA/ PTEN-altered MpBC patients (Cohort A), and * the efficacy of MEN1611 as monotherapy as determined by the objective response rate (ORR) at 6 weeks in unresectable locally advanced or metastatic HR-known/HER2-negative, PIK3CA/ PTEN-altered MpBC patients (Cohort B). Upon meeting all selection criteria, 28 patients will be enrolled as follows: \- Cohort A: A run-in phase for safety and tolerability of MEN1611 in combination with eribulin will be conducted in this patient population (N=3). A Steering Committee decision/agreement is needed, after reviewing all toxicities, to expand this cohort with 11 additional patients (up to N=14). Cohort B will be run only if positive finding in Cohort A, defined as ≥ 6 patients (42.9%) with achieved clinical benefit (CB) among 14 first recruited patients. \- Cohort B: Simon's two-stage minimax design. Stage I (N=7) will be initiated with MEN1611 monotherapy. This cohort will be stopped for futility if no responders (no complete response \[CR\] or partial response \[PR\]) are observed after 2 cycles among the first 7 patients included. Otherwise, Cohort B will be expanded with 7 additional patients for Stage II (up to N=14).

Conditions

• Breast Cancer
• Advanced Breast Cancer
• Metastatic Breast Cancer

Interventions

Type	Name	Description
DRUG	MEN1611	MEN1611 is a potent, orally bioavailable selective inhibitor of the class I phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) with a novel structure which exhibits a strong inhibitory activity especially against the PI3K catalytic subunit alpha (PIK3CA), with potential antineoplastic activity. PI3K alpha inhibitor MEN1611 selectively binds to and inhibits PIK3CA and its mutated forms in the PI3K/Akt (protein kinase B)/mammalian target of rapamycin (mTOR) pathway.
DRUG	Eribulin	Eribulin mesylate (eribulin), a non-taxane inhibitor of microtubule dynamics of the halichondrin class of antineoplastics, suppresses microtubule growth and sequesters tubulin into nonfunctional aggregates, preventing mitotic spindle formation with subsequent G2-M stop and apoptosis.

Timeline

• Start date: 2023-05-24
• Primary completion: 2026-04-01
• Completion: 2027-07-01
• First posted: 2023-04-12
• Last updated: 2026-03-10

Locations

13 sites across 1 country: Spain