Study of Cabiralizumab in Combination With Nivolumab in Patients With Selected Advanced Cancers (FPA008-003)

Five Prime Therapeutics

Status and phase: Completed; Phase 1

Conditions: Advanced Solid Tumors; Non-small Cell Lung Cancer; Malignant Glioma; Renal Cell Carcinoma; Ovarian Cancer; Head and Neck Cancer; Pancreatic Cancer

Treatments: Biological: Cabiralizumab; Biological: Nivolumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02526017

FPA008-003

Details and patient eligibility

About

Phase 1a/1b does-escalation study of cabiralizumab alone and with nivolumab in advanced solid tumors.

Full description

This is a phase 1a/b single-arm, open-label study to evaluate safety, tolerability, pharmacokinetics (PK), and clinical benefit of cabiralizumab in combination with nivolumab in patients with selected advanced cancers.

Enrollment: 313 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients must have at least one measurable lesion at baseline by computed tomography (CT) or magnetic resonance imaging (MRI) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.
• Patients must have had progressive disease on, after, or refused, appropriate approved therapy for their tumor type.
• Patients must have histologically or cytologically confirmed solid tumor that is locally recurrent or metastatic and has progressed following standard treatment or is not appropriate for standard treatment
• Understand and sign an Institutional review board/Independent ethics committee (IRB/IEC)-approved informed consent form (ICF) prior to any study-specific evaluation
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Willing and able to comply with all study procedures

Exclusion criteria

• Current or history of clinically significant muscle disorders (e.g., myositis), recent unresolved muscle injury, or any condition known to elevate serum creatine kinase (CK) levels
• Decreased cardiac function with New York Heart Association (NYHA) > Class 2
• Uncontrolled or significant heart disorder such as unstable angina
• Significant abnormalities on electrocardiogram (ECG) at screening. Fridericia's correction formula for QT interval (QTcF) > 450 msec for males or > 470 msec for females at screening
• History of anti-drug antibodies, severe allergic, anaphylactic, or other infusion-related reaction to a previous biologic agent
• Positive test for latent tuberculosis (TB) at screening (Quantiferon test) or evidence of active TB
• Patients with abnormal serum chemistry values, which in the opinion of the Investigator is considered to be clinically significant, will be excluded from the study
• Lack of peripheral venous or central venous access or any condition that would interfere with drug administration or collection of study samples
• Any uncontrolled medical condition or psychiatric disorder which, in the opinion of the Investigator, would pose a risk to patient safety or interfere with study participation or interpretation of individual patient results
• Pregnant or breastfeeding
• Current unresolved infection or history of chronic, active, clinically significant infection (viral, bacterial, fungal, or other) which, in the opinion of the Investigator, would preclude the patient from exposure to a biologic agent or pose a risk to patient safety
• Prior exposure to any colony stimulating factor 1 receptor (CSF1R) pathway inhibitors

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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313 participants in 3 patient groups

Phase 1a Monotherapy Dose Escalation

Experimental group

Description:

Cabiralizumab administered at 2 mg/kg every 2 weeks (Q2W), 4 mg/kg Q2W and 6 mg/kg Q2W in participants with any solid tumor.

Treatment:

Biological: Cabiralizumab

Phase 1a Combination Therapy Dose Escalation

Experimental group

Description:

Nivolumab 3 mg/kg Q2W + cabiralizumab at the following doses: 1 mg/kg, 2 mg/kg, 4 mg/kg, and 6 mg/kg Q2W. Also nivolumab 3 mg/kg + cabiralizumab 4 mg/kg every 3 weeks (Q3W). Participants with any solid tumor.

Treatment:

Biological: Nivolumab

Biological: Cabiralizumab

Phase 1b Combination Therapy Dose Expansion

Experimental group

Description:

The expansion phase would use the recommended dose determined in Phase 1a: cabiralizumab 4 mg/kg + nivolumab 3 mg/kg Q2W. Participants are enrolled for the following advanced cancer types: non-small cell lung cancer (anti-programmed cell death 1 \[PD1\] targeted drug naïve), non-small cell lung cancer (prior treatment with anti-PD-1), pancreatic cancer, ovarian cancer, renal cell cancer, glioblastoma, and melanoma.

Treatment:

Biological: Nivolumab

Biological: Cabiralizumab