A Phase 2 Study of Neratinib and Neratinib Plus Temsirolimus in Patients With Non-Small Cell Lung Cancer Carrying Known HER2 Activating Mutations
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Puma Biotechnology, Inc.
- Enrollment
- 62
- Locations
- 21
- Primary Endpoint
- Objective Response Rate (ORR)
Study Overview
Brief Summary
This is a Phase 2, therapeutic-exploratory, adaptive design, open-label, multicenter, multinational study evaluating neratinib monotherapy and neratinib plus temsirolimus combination therapy in patients with non-small cell lung cancer (NSCLC) who have documented somatic HER2 mutations.
Detailed Description
This is a Phase 2, therapeutic-exploratory, adaptive design, open-label, multicenter, multinational study evaluating neratinib monotherapy and neratinib plus temsirolimus combination therapy in patients with NSCLC and documented somatic HER2 mutations. Patients randomized at study entry into 1 of 2 treatment arms:
- Arm A: neratinib 240 mg orally once daily
- Arm B: neratinib 240 mg orally once daily plus temsirolimus 8 mg once weekly by intravenous (IV) infusion
In the case of disease progression, patients initially assigned to neratinib monotherapy arm given option to add temsirolimus 8 mg IV once weekly.
Patients on combination therapy given option to dose-escalate temsirolimus to 15 mg/week at the end of first cycle of treatment, if well tolerated and at the physician's discretion. If neratinib 240 mg/day plus temsirolimus 15 mg/week dose not well tolerated, patient subsequently dose reduced back to neratinib 240 mg/day plus temsirolimus 8 mg/week.
Dosing continuous on nominal 3-week cycles until evidence of progressive disease, unacceptable toxicity, or patient withdrawal of consent.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
neratinib monotherapy
240 mg once daily with food, continuously in 21 day cycles
Intervention: neratinib (Drug)
neratinib plus temsirolimus
240 mg neratinib plus 8 mg temsirolimus IV with optional dose escalation to 15 mg temsirolimus
Intervention: neratinib (Drug)
neratinib plus temsirolimus
240 mg neratinib plus 8 mg temsirolimus IV with optional dose escalation to 15 mg temsirolimus
Intervention: temsirolimus (Drug)
Outcomes
Primary Outcomes
Objective Response Rate (ORR)
Time Frame: From randomization to last tumor assessment, assessed up to 116.5 weeks. For the Neratinib arm, only tumor assessments prior to crossover were included.
ORR is defined as proportion of subjects who achieved confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. A complete or partial response must be confirmed no less than 4-weeks after the criteria for response are initially met.
Secondary Outcomes
- Clinical Benefit Rate (CBR)(From randomization to last tumor assessment, assessed up to 116.5 weeks. For the Neratinib arm, only tumor assessments prior to crossover were included.)
- Progression Free Survival (PFS)(From randomization to last tumor assessment, assessed up to 116.5 weeks. For the Neratinib arm, only tumor assessments prior to crossover were included.)
- Duration of Response (DOR)(From randomization to last tumor assessment, assessed up to 116.5 weeks. For the Neratinib arm, only tumor assessments prior to crossover were included.)
- Overall Survival (OS)(From randomization to death or end of long term follow-up, assessed up to 31.8 months.)