Study of safety & efficacy of the combination of LJM716 & BYL719 in patients with previously treated esophageal squamous cell carcinoma (ESCC)

Phase 1

• Conditions: esophageal squamous cell carcinoma; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2012-005624-15-GB
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-06-06
• Last Update Posted: 21 August 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

- Histologically confirmed ESCC
- No more than one prior chemotherapy regimen for recurrent or metastatic ESCC (for Phase II only).
- Progression during or after platinum-based therapy for recurrent or metastatic ESCC, or recurrence within 6 months of platinumbased chemotherapy or chemoradiotherapy for localized disease.
Other protocol-defined inclusion criteria may apply.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 62
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 35

Exclusion Criteria

- Patients who received prior PI3K inhibitor or anti-HER3 antibody treatment, including bi-specific antibodies with HER3 as one of the targets (patients with prior exposure to pertuzumab or EGFR-targeted agents are eligible)
- Patients who do not have an archival or fresh tumor sample (or sections of it)
available or readily obtainable.
- Patients with central nervous sytem (CNS) metastatic involvement.
- Patients who have received prior systemic anti-cancer treatment, such as cyclical chemotherapy or biological therapy within a period of time that is shorter than the cycle length used for that treatment (e.g. 6 weeks for nitrosourea, mitomycin-C) prior to starting study treatment.
- Patients who have received definitive radiotherapy = 4 weeks prior to starting study drug, who have not recovered from side effects of such therapy and/or from whom = 30% of the bone marrow was irradiated.
Other protocol-defined exclusion criteria may apply.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To study the safety and efficacy of the combination of LJM716 and BYL719 against currently available treatments of physician’s choice in previously treated ESCC patients;Secondary Objective: tolerability, PFS, OOS;Primary end point(s): 1. Phase Ib primary end point: Incidence rate of DLTs.<br>2. Phase II primary end point: Progression free survival (PFS);Timepoint(s) of evaluation of this end point: 1. approximately 8 months<br>2. Baseline, every 6 weeks until disease progression

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. Safety and tolerability of the LJM716-BYL719<br>2. Best overall response (BOR), per RECIST 1.1 (Ph 1b )<br>3. Plasma concentration versus time profiles; Plasma PK parameters of LJM716, BYL719<br>4. Overall response rate (ORR) per RECIST 1.1 (Ph 1b )<br>5. Duration of response (DOR) per RECIST 1.1 (Ph 1b )<br>6. Disease control rate (DCR) per RECIST 1.1 (Ph 1b )<br>7. Overall survival (OS) per RECIST 1.1 (for Ph 1b )<br>8. Progression free survival (PFS) per RECIST 1.1 (Ph 1b );Timepoint(s) of evaluation of this end point: 1. Baseline, every 21 days until end of study (about 5 months)<br>2. Baseline, every 21 days until end of treatment (about 4 months)<br>3. Baseline, 2hr,4hr,8hr,24hr,48hr,96hr, 168 hr, every 21 days for 10 cycles (21 days each) and at end of treatment (about 4 months)<br>4-6. Baseline, every 21 days until end of treatment (about 4 months)<br>7-8. Baseline, every 21 days until end of study (about 5 months)