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

Sponsor

Symphogen A/S (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT02924233

Collaborator

(none)

Enrollment

Arms

Actual Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Squamous Non-Small Cell Lung Cancer	Drug: Sym004 Drug: Nivolumab	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Nov 1, 2016

Actual Primary Completion Date :

Feb 1, 2017

Actual Study Completion Date :

Feb 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sym004 + nivolumab 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 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 Drug: Nivolumab Nivolumab is a humanized immunoglobulin G4 (IgG4) anti-PD-1 monoclonal antibody. Nivolumab will be administered via 60-minute infusion Q2W
Experimental: Sym004 (RP2D) + nivolumab Phase 2b, dose-expansion: Receiving Sym004 in the RP2D in combination with nivolumab (Q2W)	Drug: Sym004 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 Drug: Nivolumab Nivolumab is a humanized immunoglobulin G4 (IgG4) anti-PD-1 monoclonal antibody. Nivolumab will be administered via 60-minute infusion Q2W
Active Comparator: Nivolumab Phase 2b, dose-expansion: Receiving nivolumab monotherapy (Q2W)	Drug: Nivolumab Nivolumab is a humanized immunoglobulin G4 (IgG4) anti-PD-1 monoclonal antibody. Nivolumab will be administered via 60-minute infusion Q2W

Arm

Intervention/Treatment

Experimental: Sym004 + nivolumab

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

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

Drug: Nivolumab

Nivolumab is a humanized immunoglobulin G4 (IgG4) anti-PD-1 monoclonal antibody. Nivolumab will be administered via 60-minute infusion Q2W

Experimental: Sym004 (RP2D) + nivolumab

Phase 2b, dose-expansion: Receiving Sym004 in the RP2D in combination with nivolumab (Q2W)

Drug: Sym004

Drug: Nivolumab

Nivolumab is a humanized immunoglobulin G4 (IgG4) anti-PD-1 monoclonal antibody. Nivolumab will be administered via 60-minute infusion Q2W

Active Comparator: Nivolumab

Phase 2b, dose-expansion: Receiving nivolumab monotherapy (Q2W)

Drug: Nivolumab

Nivolumab is a humanized immunoglobulin G4 (IgG4) anti-PD-1 monoclonal antibody. Nivolumab will be administered via 60-minute infusion Q2W

Outcome Measures

Primary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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