A Phase Ib/II Study of the Combination of BYL719 Plus AMG 479 in Adult Patients With Selected Solid Tumors

Novartis

Status and phase: Terminated; Phase 2; Phase 1

Conditions: PIK3CA Amplified Advanced Solid Tumors; PIK3CA Mutated Advanced Solid Tumors

Treatments: Drug: AMG 479; Drug: BYL719

Study type: Interventional

Funder types: Industry

Identifiers

NCT01708161

2012-001962-13 (EudraCT Number)

CBYL719X2105J

Details and patient eligibility

About

This was a multi-center, open-label, phase Ib/II study. The aim of the phase Ib part was to estimate the MTD(s) and/or identify the recommended phase II dose(s) (RP2Ds) for the combination of BYL719 and AMG 479 (ganitumab), followed by the phase II part to assess the clinical efficacy and to further assess the safety of the combination in selected patient populations. Patients were to be treated until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. All patients were to be followed up. At a minimum, patients must have completed the safety follow-up assessments 30 days after the last dose of the study treatment.

Full description

This was a multi-center, open-label, phase Ib/II study. The aim of the phase Ib part was to estimate the MTD(s) and/or identify the recommended phase II dose(s) (RP2Ds) for the combination of BYL719 and AMG 479 (ganitumab), followed by the phase II part to assess the clinical efficacy and to further assess the safety of the combination in selected patient populations. The dose escalation part of the study were to be guided by a Bayesian Logistic Regression Model (BLRM).

Once MTD/RP2D had been determined, patients were to be enrolled in two Phase II arms. Patients with PIK3CA mutated or amplified hormone receptor positive breast carcinoma were to be enrolled in Arm 1; patients with PIK3CA mutated or amplified ovarian carcinoma were to be enrolled in Arm 2. Patients were to be treated until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. All patients were to be followed up. At a minimum, patients must have completed the safety follow-up assessments 30 days after the last dose of the study treatment.

Enrollment: 47 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key inclusion criteria:

• Written informed consent.
• Patients aged ≥ 18 years (male or female).
• Patients with the following histologically/cytologically-confirmed advanced solid tumors with documented somatic PIK3CA mutations or amplifications in tumor tissue:
• Hormone receptor positive breast carcinoma
• Ovarian carcinoma
• Other tumors upon agreement with sponsor
• Adequate organ function
• Negative serum pregnancy test

Key exclusion criteria:

• Patients with known history of severe infusion reactions to monoclonal antibodies.
• Patients with primary CNS tumor or CNS tumor involvement.
• History of thromboembolic event requiring full-dose anti-coagulation therapy any time prior to enrollment.
• Clinically significant cardiac disease.
• History of another malignancy within last 2 years.
• Pregnant or nursing (lactating) women.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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47 participants in 1 patient group

BYL719 + AMG 479

Experimental group

Description:

For: Dose escalation phase/Phase II Expansion Phase. Cohorts of 3-6 patients were to be enrolled sequentially until an MTD or a recommended Phase II dose were defined. All patients were to receive the combination treatment. Sequential cohorts may receive different doses of the combination. In the Phase II expansion, all patients were to receive the same combination treatment.

Treatment:

Drug: BYL719

Drug: AMG 479