Study of Carotuximab (TRC105) Plus Nivolumab in Patients With Metastatic NSCLC

NCT03181308 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 105LC102
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 2

Brief Summary

This is a multi-center, open-label, nonrandomized, dose-escalation, Phase 1b study of carotuximab in combination with standard dose nivolumab in patients with NSCLC that has progressed on or after platinum-based chemotherapy or PD-1/PD-L1 checkpoint inhibition, as a single agent or with chemotherapy.

Conditions

Carcinoma, Non-Small-Cell Lung

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Dose Limiting Toxicity (DLT)

  For DLT evaluation, severity (grade) was classified according to common terminology criteria for adverse events version 4.03 (CTCAE v4.03). DLTs were defined as grade 4 neutropenia persisting for ≥ 5 days, Febrile neutropenia: Grade 4 neutropenia with fever \>38.5ºC both sustained over a ≥24-hour period, neutropenic infection (grade ≥ 3 neutropenia with grade ≥ 3 infection), anemia ≥ grade 4, Grade ≥4 thrombocytopenia or Grade ≥3 thrombocytopenia with Grade ≥3 hemorrhage, or grade 3 or 4 nonhematologic toxicity with the following exceptions: asymptomatic electrolyte abnormality that is corrected to Grade 1 or better in \<72 hours, grade 3 headache lasting \<48 hours. See protocol for Immune related DLT criteria.

  Approximately 2-8 months

Secondary Outcomes (4)

• Response Rate

  Approximately 2-8 months

• Trough Carotuximab (TRC105) Concentrations

  8 weeks

• Development of Immunogenicity Antibodies

  Approximately 2-8 months

• Trough Nivolumab Concentrations

  Approximately 2-8 months

Study Arms (1)

TRC105 plus Nivolumab

EXPERIMENTAL

Drug: Carotuximab (TRC105); Drug: OPDIVO

Interventions

Carotuximab (TRC105) DRUG

Anti Endoglin Antibody

Also known as: TRC105

TRC105 plus Nivolumab

OPDIVO DRUG

Programmed Death Receptor-1

Also known as: Nivolumab

TRC105 plus Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed metastatic non-small cell lung cancer (NSCLC) with disease recurrence or progression during or after prior platinum-containing doublet chemotherapy regimen
• Histologically confirmed metastatic non-small cell lung cancer (NSCLC) that has relapsed following prior PD-1/PD-L1 checkpoint inhibitor therapy without Grade 3 immune-related toxicity, which may or may not have included concurrent chemotherapy. Relapse following prior PD-1 checkpoint therapy is defined as confirmed progressive disease following stable disease or better (e.g., iSD, iPR, iCR) on at least 1 tumor assessment.
• Patients with an active oncogenic driver (e.g., epidermal growth factor \[EGFR\], activin-receptor-like kinase 1 \[ALK1\], or the proto-oncogene tyrosine-protein kinase ROS-1) must have progressed on or after a US Food and Drug Administration (FDA)-approved therapy for that aberration
• Patients who received adjuvant or neoadjuvant platinum-doublet chemotherapy (after surgery and/or radiation therapy) and developed recurrent or metastatic disease within 6 months of completing therapy are eligible.
• Patients with recurrent disease \> 6 months after adjuvant or neoadjuvant platinum-based chemotherapy, who also subsequently progressed during or after a platinum- doublet regimen given to treat the recurrence, are eligible.
• Formalin fixed, paraffin-embedded (FFPE) tumor tissue block that permits the preparation of 20 unstained slides of tumor sample (archival) - Biopsy must be excisional, incisional, or core. Needle aspiration is insufficient. In cases where archival tumor tissue is unavailable, tumor biopsy will be required prior to treatment initiation.
• Programmed death ligand 1 (PD-L1) determination by validated immunohistochemistry assay
• Measurable disease by iRECIST
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
• Resolution of all acute adverse events resulting from prior cancer therapies to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade ≤ 1 or baseline (except alopecia or neuropathy)
• Adequate organ function
• Willingness and ability to consent for self to participate in study
• Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures

You may not qualify if:

• Autoimmune disease requiring treatment within the past twelve months.
• Condition requiring systemic treatment with either corticosteroids
• History or active interstitial lung disease
• Prior therapy with T-cell therapy, including an immune checkpoint inhibitor. Patients who received prior immune checkpoint inhibitor therapy are allowed in Expansion Cohort 2 in the absence of recurrent grade 2 (except skin, endocrine and constitutional symptoms), or ≥ 3 immune-related toxicity).
• Prior treatment with carotuximab
• Current treatment on another therapeutic clinical trial
• Receipt of systemic anticancer therapy, including investigational agents, within 28 days prior to study treatment (Note: If anticancer therapy was given within 28 days prior to starting study treatment, patients are not excluded if ≥ 5 times the elimination half-life of the drug has elapsed.)
• Major surgical procedure or significant traumatic injury within 4 weeks prior to study treatment, and must have fully recovered from any such procedure; and no date of surgery (if applicable) or anticipated need for a major surgical procedure planned within the next 6 months
• Chest radiotherapy ≤ 28 days, wide field radiotherapy ≤ 28 days (defined as \> 50% of volume of pelvic bones or equivalent), or limited field radiation for palliation ≤ 14 days prior to study treatment - Such patients must have recovered adequately from any side effects of such therapy.
• Hypertension defined as blood pressure (BP) systolic \> 150 or diastolic \> 90 mm Hg (Note: Initiation or adjustment of antihypertensive medication prior to study entry is allowed provided that the average of 3 BP readings prior to study treatment is ≤150/90 mm Hg.)
• Ascites or pericardial effusion that required intervention within 3 months prior to study treatment
• History of brain involvement with cancer, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease
• Angina, myocardial infarction (MI), symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack TIA), arterial embolism, pulmonary embolism, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery bypass grafting (CABG) within 6 months prior to study treatment
• Deep venous thrombosis within 6 months prior to study treatment, unless the patient is anti-coagulated without the use of warfarin for ≥2 weeks prior to study treatment; in this situation, low molecular weight heparin is preferred
• Active bleeding or pathologic condition that carries a high risk of bleeding (e.g., hereditary hemorrhagic telangiectasia)

Sponsors & Collaborators

• Tracon Pharmaceuticals Inc.: lead

Study Sites (2)

University of Alabama, Birmingham

Birmingham, Alabama, 35294, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Related Links

• TRACON Pharmaceuticals

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

carotuximab; Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Monitor
• Organization: TRACON Pharmaceuticals Inc

clinicaltrials@traconpharma.com

8585500780

Study Officials

• Charles Theuer, MD, PhD

  Medical Monitor

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2017
• First Posted: June 8, 2017
• Study Start: November 9, 2017
• Primary Completion: July 22, 2019
• Study Completion: July 22, 2019
• Last Updated: June 24, 2020
• Results First Posted: June 24, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)