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MEN1611 orally (PO) 48 mg twice daily (BID) (2 intakes of 3x16 mg capsules, for a total daily dose of 96 mg MEN1611 free-base) during each 21-day cycle combined with eribulin mesylate 1.4 mg/m2 (equivalent to eribulin 1.23 mg/m2 when expressed as a free base) administered intravenously (IV) over 2 to 5 minutes on days 1 and 8 of every 21-day cycle (CXD1 and CXD8).

A run-in phase for safety and tolerability of MEN1611 in combination with eribulin will be conducted after the first 2 cycles on the first 3 patients. Upon Steering Committee agreement the cohort A will be expanded up to N=14 (11 additional patients).

Patients will receive treatment until disease progression, unacceptable toxicity, death, discontinuation from the study treatment for any other reason, withdrawal of consent, or study termination.

Cohort B will be run only if there will be positive finding in Cohort A, defined as ≥ 6 patients (42.9%) with CB (CR or PR) among 14 recruited patients.

Stage I (N =7): MEN1611 monotherapy 48 mg PO BID (2 intakes of 3x16 mg capsules, for a total daily dose of 96 mg MEN1611 free-base) during each 21-day cycle.

After 2 cycles, ORR will be determined per RECIST v1.1 criteria:

* Patients experiencing CR or PR will continue with MEN1611 monotherapy.
* Patients experiencing stable disease (SD) will continue with MEN1611 monotherapy or will be treated with MEN1611 plus eribulin mesylate 1.4 mg/m2 (1.23 mg/m2 eribulin free base), IV on CXD1 and CXD8, under investigator's decision.
* An interim analysis will assess the viability of this part of the trial. Cohort B will be stopped for futility if no responders (no CR or PR) are observed among the 7 patients included.

Stage II: same as stage I with 7 additional patients (total N=14).

Patients will receive treatment until disease progression, unacceptable toxicity, death, discontinuation from the study treatment for any other reason, withdrawal of consent, or study termination.

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.

MEN1611

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.

Eribulin

Olalla Ballesteros

Susana Vitorino

Isabel Blancas, MD

Isabel Blancas

Manuel Ruiz Borrego, MD

Manuel Ruiz Borrego

Magda Palka, MD

Ainhara Lahuerta Martinez, MD

Isaura Fernández Pérez, MD

Maria Jose Villanueva

Isaura Fernández Pérez

Agostina Stradella

Esther Zamora

Angel Guerrero, MD

José Pérez, MD

Antonio Llombart-Cussac, MD

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).

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).

Multicenter, two-cohort, non-comparative, open-label, phase II clinical trial.

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

Phase II Study for PIK3CA/PTEN-altered Advanced Metaplastic Breast Cancer Treated With MEN1611 Monotherapy or in Combination With Eribulin

ORR, defined as the proportion of patients with confirmed CR or PR, of patients in the Cohort B who received MEN1611 in combination with eribulin treatment, as determined per RECIST v1.1 criteria.

CBR, defined as the percentage of patients who experience a CR, PR or SD, of patients in Cohort B who received MEN1611 in combination with eribulin treatment, as determined per RECIST v1.1 criteria.

TTR, defined as the time from the start of treatment to the first objective tumor response (tumor shrinkage of ≥ 30%) of patients in the Cohort B who received MEN1611 in combination with eribulin treatment, as determined per RECIST v1.1 criteria.

DoR, defined as the time from the first dose of study drugs until death from any cause, of patients in Cohort B who received MEN1611 in combination with eribulin treatment, as determined per RECIST v1.1 criteria.

PFS, defined as the time from the first dose of study drugs until objective tumor progression or death, whichever occurs first, of patients in the Cohort B who received MEN1611 in combination with eribulin treatment, as determined per RECIST v1.1 criteria.

OS, defined as the time from the first dose of study drugs until death from any cause of patients in the Cohort B who received MEN1611 in combination with eribulin treatment.

To evaluate the incidence and severity of adverse events of MEN1611 in combination with eribulin treatment in cohort B patients, in accordance to NCI-CTCAE v.5.0.

CBR, defined as the percentage of patients who experience a complete response (CR), partial response (PR) or stable disease (SD) in cohort A for at least 12 weeks after the start of MEN1611 in combination with eribulin treatment, as determined locally by the investigator per RECIST v1.1 criteria.

ORR, defined as the percentage of patients in cohort B with confirmed CR or PR at 6 weeks after the start of MEN1611 treatment, as determined per RECIST v1.1 criteria.

ORR, defined as the proportion of patients with confirmed CR or PR who received MEN1611 in combination with eribulin treatment in Cohort A, as determined per RECIST v1.1 criteria.

TTR, defined as the time from the start of MEN1611 in combination with eribulin treatment to the first objective tumor response (tumor shrinkage of ≥ 30%) of patients in Cohort A, as determined per RECIST v1.1 criteria.

DoR, defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first, of patients in Cohort A who received MEN1611 in combination with eribulin treatment, as determined per RECIST v1.1 criteria.

PFS, defined as the time from the first dose of study drugs until objective tumor progression or death, whichever occurs first, of patients in Cohort A who received MEN1611 in combination with eribulin treatment, as determined per RECIST v1.1 criteria.

OS, defined as the time from the first dose of study drugs until death from any cause of patients in Cohort A who received MEN1611 in combination with eribulin treatment.

ORR, defined as the proportion of patients with confirmed CR or PR, of patients in Cohort B who received MEN1611 in monotherapy treatment, as determined per RECIST v1.1 criteria.

CBR, defined as the percentage of patients who experience a CR, PR or SD, of patients in the Cohort B who received MEN1611 in monotherapy treatment, as determined per RECIST v1.1 criteria.

TTR, defined as the time from the start of treatment to the first objective tumor response (tumor shrinkage of ≥ 30%), of patients in Cohort B who received MEN1611 in monotherapy treatment, as determined per RECIST v1.1 criteria.

DoR, defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first, of patients in Cohort B who received MEN1611 in monotherapy treatment, as determined per RECIST v1.1 criteria.

PFS, defined as the time from the first dose of study drugs until objective tumor progression or death, whichever occurs first, of patients in the Cohort B who received MEN1611 in monotherapy treatment, as determined per RECIST v1.1 criteria.

OS, defined as the time from the first dose of study drugs until death from any cause of patients in Cohort B who received MEN1611 in monotherapy treatment.

To evaluate the incidence and severity of adverse events of MEN1611 in combination with eribulin treatment of patients in cohort A, in accordance to NCI-CTCAE v.5.0.

To evaluate the incidence and severity of adverse events of MEN1611 as monotherapy treatment of patients in Cohort B, in accordance to NCI-CTCAE v.5.0.

Menarini Group

MedSIR

Digestive System Diseases

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

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Pharmaceutical Solutions

Irinotecan

Cetuximab

Fluorouracil

Oxaliplatin

Antineoplastic Agents, Immunological

MEN1611 oral dose administered twice daily for a continuous 28-day cycle.

Cetuximab solution for infusion administered weekly via IV infusion.

Josep Tabernero, MD PhD

Open-label, dose-confirmation and cohort expansion, multicentre, Phase Ib/II study to assess the anti-tumour activity and safety of MEN1611 in combination with cetuximab for the treatment of patients with PIK3CA mutated metastatic colorectal cancer.

This Phase Ib/II study will investigate the anti-tumour activity and safety of daily oral doses MEN1611 in combination with cetuximab in female and male patients affected by PIK3CA mutated, N-K-RAS wild-type and BRAF wild-type metastatic colorectal cancer.

MEN1611 is a potent, selective Class I phosphoinositide 3-kinase (PI3K) inhibitor. The Maximum Tolerated Dose (MTD) of MEN1611 given as single agent was assessed in a phase I trial in patients with advanced solid tumors.

This Phase Ib/II will start with a dose confirmation part (Step 1) to identify the RP2D of MEN1611 given in combination with cetuximab.

The study will continue with a cohort expansion (Step 2) to explore the anti-tumour activity of the selected MEN1611 dose level combined with cetuximab with further assessment of their safety and tolerability.

Step 1: Confirmation of Dose for Cohort Expansion / Step 2: Cohort Expansion

MEN1611 With Cetuximab in Metastatic Colorectal Cancer (C-PRECISE-01)

Open-label, Multicentre, Phase Ib/II Study of MEN1611, a PI3K Inhibitor, and Cetuximab in Patients With PIK3CA Mutated Metastatic Colorectal Cancer Failing Irinotecan, Oxaliplatin, 5-FU and Anti-EGFR Containing Regimens

Determination of the recommended phase II dose of MEN1611 when administered orally in combination with cetuximab to patients with PIK3CA mutated colorectal cancer failing irinotecan, oxaliplatin, 5-FU and anti-EGFR containing regimens.

Assessment of the anti-tumour activity of MEN1611 in combination with cetuximab in patients with PIK3CA mutated metastatic colorectal cancer failing irinotecan, oxaliplatin, 5-FU and anti-EGFR containing regimens.

Assessment of the tolerability of MEN1611 in combination with cetuximab according to NCI CTCAE v5.0.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
PIK3CA/PTEN-altered Advanced Breast Cancer Treated With MEN1611 Monotherapy or in Combination With Eribulin	NCT05810870	Breast Cancer Advanced Breast... Metastatic Brea...	MEN1611 Eribulin	18 Years -	MedSIR
MEN1611 With Cetuximab in Metastatic Colorectal Cancer (C-PRECISE-01)	NCT04495621	Metastatic Colo...	MEN1611 Cetuximab	18 Years -	Menarini Group

Spots Global Cancer Trial Database for men1611

Every month we try and update this database with for men1611 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for men1611

Every month we try and update this database with for men1611 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for men1611 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.