Sym004 in Combination With Nivolumab Versus Nivolumab Monotherapy in EGFR-amplified Squamous Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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This is a phase 1b/2b study investigating the safety and preliminary antitumor effects of Sym004 in combination with nivolumab versus nivolumab monotherapy when administered every second week.

Official Title
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An Open-label, Randomized, Multicenter, Phase 1b/2b Trial Investigating the Safety and Preliminary Antitumor Effects of Sym004 in Combination With Nivolumab Versus Nivolumab Monotherapy in EGFR-amplified Squamous Non-Small Cell Lung Cancer

Conditions
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Squamous Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Sym004
* Drug: Nivolumab


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Signed and dated written informed consent Male or female ≥18 years of age at the time of informed consent Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Life expectancy >3 months assessed during Screening Histologically or cytologically confirmed, locally advanced or metastatic squamous NSCLC Main Exclusion Criteria: Any antineoplastic agent (standard or investigational) within 2 weeks prior to starting trial treatment Radiosurgery or radiotherapy for target lesions within 2 weeks prior to starting trial treatment Prophylactic use of hematopoietic growth factors within 1 week prior to starting trial treatment Active Central Nervous System (CNS) metastases or carcinomatous meningitis Women who are pregnant Women who are breastfeeding

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
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sym004 + nivolumab<br>Phase 1b, dose-escalation: Dose Level 1: Sym004 + nivolumab (Q2W) Dose Level 2: Sym004 + nivolumab (Q2W) Dose Level -1: Sym004 + nivolumab, if needed | Drug: Sym004<br>* Sym004 is a 1:1 mixture of two monoclonal antibodies (mAbs) which bind to two non-overlapping epitopes of the Epidermal Growth Factor Receptor (EGFR). Sym004 will be administered at different dose-levels via infusion Q2W<br>Drug: Nivolumab<br>* Nivolumab is a humanized immunoglobulin G4 (IgG4) anti-PD-1 monoclonal antibody. Nivolumab will be administered via 60-minute infusion Q2W<br>|
| Experimental: Sym004 (RP2D) + nivolumab<br>Phase 2b, dose-expansion: Receiving Sym004 in the RP2D in combination with nivolumab (Q2W) | Drug: Sym004<br>* Sym004 is a 1:1 mixture of two monoclonal antibodies (mAbs) which bind to two non-overlapping epitopes of the Epidermal Growth Factor Receptor (EGFR). Sym004 will be administered at different dose-levels via infusion Q2W<br>Drug: Nivolumab<br>* Nivolumab is a humanized immunoglobulin G4 (IgG4) anti-PD-1 monoclonal antibody. Nivolumab will be administered via 60-minute infusion Q2W<br>|
| Active Comparator: Nivolumab<br>Phase 2b, dose-expansion: Receiving nivolumab monotherapy (Q2W) | Drug: Nivolumab<br>* Nivolumab is a humanized immunoglobulin G4 (IgG4) anti-PD-1 monoclonal antibody. Nivolumab will be administered via 60-minute infusion Q2W<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1b: Determination of the Dose-Limiting Toxicities (DLT) and the MTD and/or RP2D of escalating doses of Sym004 in combination with a standard dose of nivolumab |  | 1 year | 
| Phase 2b: Evaluation of the antitumor effects of the RP2D of Sym004 when administered in combination with a standard dose of nivolumab as measured by Response Rate |  | 1.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Squamous, Non-Small Cell Lung Cancer, NSCLC