A Study Evaluating RO5479599 in Combination With Carboplatin and Paclitaxel in Participants With Advanced or Metastatic Non-Small-Cell Lung Cancer (NSCLC) of Squamous Histology

Study Overview
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Brief Summary
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A multi-center Phase Ib/II study of the combination of RO5479599 with carboplatin and paclitaxel once in every 3 week (q3w) regimen to evaluate the safety and tolerability.

Official Title
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Open Label Phase Ib/II, Multicenter Study of the Combination of RO5479599 With Carboplatin and Paclitaxel in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) of Squamous Histology Who Have Not Received Prior Chemotherapy or Targeted Therapy for NSCLC

Conditions
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Squamous Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Carboplatin
* Drug: Paclitaxel
* Drug: RO5479599


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with the Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 Locally advanced or metastatic (stage IIIB or IV) squamous NSCLC No prior systemic chemotherapy, targeted therapy for metastatic NSCLC Evidence of at least one radiologically measurable lesion as per RECIST version 1.1 Adequate hematological, liver and renal function Participants must agree to either remain completely abstinent or to use effective contraceptive methods from screening until 6 months after the last dose of study treatment Histologically confirmed squamous NSCLC participants eligible for enrollment must provide archival tumor biopsy tissue or if unavailable must be willing to undergo a fresh pretreatment primary tumor or metastatic biopsy Participants with Gilbert's Syndrome will be eligible for the study Exclusion Criteria: Concurrent therapy with any other investigational drug History or clinical evidence of central nervous system (CNS) primary tumors or metastases Evidence of significant, uncontrolled concomitant diseases, which could affect compliance with the protocol or interpretation of results, including uncontrolled diabetes mellitus and/or significant cardiovascular disease or uncontrolled infection Any other diseases, metabolic dysfunction, a physical examination finding or a clinical laboratory finding, giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug Major surgery or significant traumatic injury less than (<) 28 days prior to the first study treatment infusion (excluding biopsies) or anticipation of the need for major surgery during study treatment Pregnant or breast-feeding women History of other malignancies that could affect compliance with protocol or interpretation of results. Participants with malignancies diagnosed more than 5 years prior to study day one, adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer are generally eligible

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RO5479599 + Carboplatin + Paclitaxel<br>RO5479599 800 milligrams (mg) will be administered in the Safety Run-In Phase by intravenous infusion q3w on Day 1 of 3-weekly cycles (each cycle of 21 days) in combination with carboplatin (to produce an area under the curve [AUC] of 6 mg/milliliter [mL]*minute) and paclitaxel 200 mg per square meter (mg/m^2) by intravenous infusion q3w for 4 to 6 cycles. Thereafter, RO5479599 will be continued as a monotherapy (carboplatin and paclitaxel may be continued at the investigator's discretion) until disease progression, death, unacceptable toxicity, withdrawal of consent, or study termination by sponsor, whichever occurs first. | Drug: Carboplatin<br>* Carboplatin by intravenous infusion q3w for 4-6 cycles and thereafter as per investigator's discretion.<br>Drug: Paclitaxel<br>* Paclitaxel by intravenous infusion q3w until disease progression, death, unacceptable toxicity or withdrawal of consent.<br>Drug: RO5479599<br>* RO5479599 will be administered as an intravenous infusion q3w until disease progression, death, unacceptable toxicity or withdrawal of consent.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Adverse Events |  | Baseline up to Day 342 | 
| Percentage of Participants With Objective Response as Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) |  | Baseline until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first (assessed every 6 weeks from baseline [Cycle 1 Day 1] [Cycle length = 21 days] up to Day 342) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) as Assessed Using RECIST v1.1 |  | Baseline until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first (assessed every 6 weeks from baseline [Cycle 1 Day 1] [Cycle length = 21 days] up to Day 342) | 
| Overall survival (OS) |  | Baseline until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first (assessed every 6 weeks from baseline [Cycle 1 Day 1] [Cycle length = 21 days] up to Day 342) | 
| Percentage of Participants With Disease Control as Assessed by Investigator Using RECIST v1.1 |  | Baseline until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first (assessed every 6 weeks from baseline [Cycle 1 Day 1] [Cycle length = 21 days] up to Day 342) | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of RO5479599 |  | Pre-dose(Hour 0); at end of infusion (infusion duration=approximately 2 hours) on Day 1 of each cycle (cycle length= 21 days) up to end of treatment (EOT, Day 314); 3-6, 24, 72, 168, 264, 336, 432, 480 hours post-dose on Day 1 of Cycle 1,4; at Day 342 | 
| Maximum Observed Plasma Concentration (Cmax) of RO5479599 |  | Pre-dose (Hour 0) and at end of infusion (infusion duration=approximately 2 hours) on Day 1 of each cycle (cycle length= 21 days) up to EOT (Day 314); 3-6, 24, 72, 168, 264, 336, 432, 480 hours post-dose on Day 1 of Cycle 1,4; at Day 342 | 
| Trough Concentration (Ctrough) of RO5479599 |  | Pre-dose (Hour 0) on Day 1 of each cycle (cycle length = 21 days) up to EOT (Day 314) | 
| Total Clearance (CL) of RO5479599 |  | Pre-dose (Hour 0) and at end of infusion (infusion duration=approximately 2 hours) on Day 1 of each cycle (cycle length= 21 days) up to EOT (Day 314); 3-6, 24, 72, 168, 264, 336, 432, 480 hours post-dose on Day 1 of Cycle 1,4; at Day 342 | 
| Volume of Distribution at Steady State (Vss) of RO5479599 |  | Pre-dose (Hour 0) and at end of infusion (infusion duration=approximately 2 hours) on Day 1 of each cycle (cycle length= 21 days) up to EOT (Day 314); 3-6, 24, 72, 168, 264, 336, 432, 480 hours post-dose on Day 1 of Cycle 1,4; at Day 342 | 
| Accumulation Ratio (Rac) of RO5479599 |  | Pre-dose(Hour 0); at end of infusion (infusion duration=approximately 2 hours) on Day 1 of each cycle (cycle length= 21 days) up to end of treatment (EOT, Day 314); 3-6, 24, 72, 168, 264, 336, 432, 480 hours post-dose on Day 1 of Cycle 1,4; at Day 342 | 
| Terminal Elimination Half-life (t 1/2) of RO5479599 |  | Pre-dose(Hour 0); at end of infusion (infusion duration=approximately 2 hours) on Day 1 of each cycle (cycle length= 21 days) up to end of treatment (EOT, Day 314); 3-6, 24, 72, 168, 264, 336, 432, 480 hours post-dose on Day 1 of Cycle 1,4; at Day 342 | 
| Concentration of RO5479599 at the Time of Tumor Progression (Cprog) |  | At tumor progression (any time between Baseline and Day 342) | 
| Concentration of RO5479599 at the Time of Tumor Response (Complete Response or Partial Response) |  | At the time of tumor response (anytime between baseline and Day 342) | 
| Concentration of RO5479599 at the Time of Toxicity |  | At the time of toxicity (anytime between baseline and Day 342) | 
| Concentration of RO5479599 at the Time of Infusion-related Reactions (IRRs) or Hypersensitivity Reaction |  | At the time of IRRs or Hypersensitivity Reaction (anytime between baseline and Day 342) |