Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Breast Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Ovarian Cancer

Ovarian Epithelial Cancer

All Drugs and Chemicals

Antibodies

Antibodies, Monoclonal

Immunoglobulins

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.

BYL719 is a small molecule inhibiting PI3-Kinase.

BYL719

AMG 479 is a monoclonal antibody directed against IGF1-R.

AMG 479

Novartis Pharmaceuticals

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.

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.

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

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

The antitumor activity of alpelisib in combination with ganitumab in patients with PIK3CA mutated or amplified hormone receptor positive (HR+) breast (arm 1) or ovarian (arm 2) cancer.

Overall response rate is defined as the proportion of patients who have a best overall response of complete response or partial response assessed per RECIST 1.1.

The anti-tumor activity of alpelisib and ganitumab in combination as per RECIST 1.1

the antitumor activity of alpelisib in combination with ganitumab in patients with PIK3CA mutated or amplified hormone receptor positive (HR+) breast (arm 1) or ovarian (arm 2) cancer.

Phase II only, Cycle 1 Day 1 through Cycle 6 Day 28; assessed at baseline and every 8 weeks thereafter

Serum concentration for BYL719 (alpelisib)

1 cycle - 28 days of treatment

Area under curve for BYL719 (alpelisib)

1 cycle - 28 days of treatment

Tmax and half life of BYL719 (Alpelisib)

1 cycle - 28 days of treatment

Serum concentration for AMG 479 (ganitumab)

1 cycle - 28 days of treatment

Area under curve for AMG 479 (ganitumab)

1 cycle - 28 days of treatment

Tmax and half life of AMG 479 (ganitumab)

1 cycle - 28 days of treatment

NantCell, Inc.

One patients with a tumor type other than Breast and Ovarian treated in the phase II part not represented.

BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors

BYL 200mg + AMG 12 mg/kg

BYL 300mg + AMG 12 mg/kg

BYL 350mg + AMG 12 mg/kg

Patients with PIK3CA mutated or amplified hormone receptor (HR) positive breat carcinoma (BC) were treated with alpelisib 300 mg once daily and ganitumab 12 mg/kg

HR + BC - Phase II

Patients with other than Breast and Ovarian cancer treated in the phase II

Ovarian - Phase II

BYL 200mg + AMG 12mg/kg

BYL 300mg + AMG 12mg/kg

BYL 350mg + AMG 12mg/kg

Patients with PIK3CA mutated or amplified hormone receptor (HR) positive breast carcinoma (BC) were treated with alpelisib 300 mg once daily and ganitumab 12 mg/kg.

HR+BC - Phase II

Patients with PIK3CA mutated or amplified ovarian cancer were treated with alpelisib 300 mg once daily and ganitumab 12 mg/kg

Patients with other than Breast and Ovarian cancer treated in the phase II part

Non-HR+BC/Ovarian - Phase II

Total

Age, Continuous

Sex: Female, Male

Race/Ethnicity, Customized

Due to the competitive landscape for anticancer therapies in ovarian and breast cancer and given the limited clinical activity observed with the study combination treatment, Novartis decided in 2014 to halt the recruitment in the trial.

Study Director

Drug hypersensitivity

Hyperglycemia

Rash maculopapular

Urticaria

Dose determining set (DDS): DDS includes all patients from the safety set who either met the minimum treatment exposure and safety evaluation requirements without experiencing DLT within Cycle 1 or experienced a DLT at any time during Cycle 1.

Dose Limiting Toxicities (DLTs) - Phase Ib

The total column "All patients" includes a patient with non-HR+BC and non-Ovarian cancer treated in the Phase II part.

All Patients - Phase

Full analysis set (FAS). The full analysis set (FAS) includes all patients who received at least one full or partial dose of alpelisib or ganitumab. Patients were analyzed according to the planned treatment combination.

Percentage of Patients With Overall Response Rate (RECIST) Based on Investigator Radiology Assessment for HR Positive Breast and Ovarian Cancer - Phase II

Complete response (CR)

Partial response (PR)

Stable disease (PD)

Progressive disease (PD)

Unknown

Number of Patients With Best Overall Response (RECIST) Based on Investigator Radiology Assessment - Phase Ib

Percentage of Patients With Disease Control Rate (RECIST) Based on Investigator Radiology Assessment - Phase Ib

All Patients - Phase II

Percentage of Patients With Disease Control Rate (RECIST) Based on Investigator Radiology Assessment for HR Positive Breast and Ovarian Cancer - Phase II

Cycle 1 Day 1

Cycle 1 day 15

Pharmacokinetic analysis set (PAS). The PAS included all patients who had at least one blood sample providing evaluable PK data. Patients were analyzed according to the dose level they actually received.

Spots Global Cancer Trial Database for cancers with a mass