Dose Escalation Trial of Bexmarilimab (FP-1305) Plus Pembrolizumab in Non-Small Cell Lung Cancer

NCT05171062 | Withdrawn Phase 1 FDA Drug

• 2 other identifiers: CTMS# 21-015320210791HU
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This study enrolls patients with Non-small cell lung cancer and treats them with the investigational drug Bexmarilimab (FP-1305) plus standard of care Pembrolizumab to block Common lymphatic endothelial and vascular endothelial receptor-1 (CLEVER-1). Treating with an antiCLEVER-1 antibody, such as bexmarilimab, could lead to immune system activation, which, in turn, may lead to cancer elimination.

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Safety and tolerability

  Measured by the number of adverse events according to the National Cancer Institute Common Terminology Criteria for Adverse events (NCI-CTCAE v. 5) ≥Grade 3 occuring during the 21 days 3 weeks) following the first dose of bexmarilimab plus pembrolizumab in Cycle 2 and related to bexmarilimab are considered dose limiting toxicity (DLT) with the following exceptions: * Grade 3 infusion reactions that resolve within 8 hours from the onset of the reaction and are not defined as a DLT * For nausea/vomiting/diarrhea, only adequately pre-treated grade 3 or 4 toxicity will qualify as DLT * For thrombocytopenia, hemorrhage is required to qualify grade 3 toxicity as DLT; grade 4 thrombocytopenia is DLT regardless of hemorrhaged * For neutropenia, fever is required to qualify grade 3 toxicity as DLT. A duration \> 5 days is required to qualify grade 4 toxicity as DLT

  Cycle 2 plus 3 weeks (21 days following the first dose of both study drugs)

• Programmed Death Cell Ligand 1 (PD-L1) level

  Measured using analysis of soluble CLEVER-1 (sClever) levels

  Cycle 1 (21 days), pre-dose levels at start of Cycle 3 (42 days)

Secondary Outcomes (1)

• Immunophenotyping

  Baseline to study end (approximately 12 months)

Other Outcomes (1)

• Objective Response Rate (ORR)

  Cycle 1 (21 days)

Study Arms (4)

Cohort 1

EXPERIMENTAL

Study patients will receive 0.1-1 mg/kg bexmarilimab (FP-1350) given in combination with Pembrolizumab 200mg IV once every three weeks. The first subject will be started on 0.1mg to establish toleration, for one dose, and then the dose will be escalated to 1mg. This subject will be included in Cohort 1 data.

Drug: bexmarilimab (FP-1305); Drug: Pembrolizumab

Cohort 2

EXPERIMENTAL

Study participants will receive 3mg/kg Bexmarilimab given in combination with Pembrolizumab 200mg IV once every three weeks. 3 participants will need to complete this level before the next cohort dosing begins.

Drug: bexmarilimab (FP-1305); Drug: Pembrolizumab

Cohort 3

EXPERIMENTAL

Study participants will receive 10 mg/kg Bexmarilimab plus pembrolizumab 200mg IV once every 3 weeks. 3 participants will need to complete this level before the next cohort dosing begins.

Drug: bexmarilimab (FP-1305); Drug: Pembrolizumab

Cohort 4

EXPERIMENTAL

Study participants will receive 30 mg/kg Bexmarilimab plus pembrolizumab 200mg IV once every 3 weeks.

Drug: bexmarilimab (FP-1305); Drug: Pembrolizumab

Interventions

bexmarilimab (FP-1305) DRUG

standard 3+3 dose escalation trial of bexmarilimab (FP-1305)

Also known as: FP-1305

Cohort 1; Cohort 2; Cohort 3; Cohort 4

Pembrolizumab DRUG

Pembrolizumab 200mg IV is administered in 4 planned bexmarilimab dose escalation cohorts

Also known as: Keytruda

Cohort 1; Cohort 2; Cohort 3; Cohort 4

Eligibility Criteria

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

You may qualify if:

• Able to provide written Informed Consent
• Aged ≥ 18 years
• Tumor sample obtained less than six months from the date of consent
• Histologically confirmed NSCLC eligible for pembrolizumab as standard of care
• Known tumor PD-L1 TPS score
• Measurable disease based on RECIST 1.1 as determined by the site
• Women of child-bearing potential must have a negative pregnancy test prior to trial entry and cycle 1 day 1 and should not be breast feeding.
• Women of child-bearing potential and men who have partners of child-bearing potential must be willing to practice highly effective contraception for the duration of the trial and for three months after the completion of treatment

You may not qualify if:

• Less than 21 days since the last dose of intravenous anticancer chemotherapy or less than five half-lives from a small molecule targeted therapy or oral anticancer chemotherapy before the first bexmarilimab administration
• Any immunotherapy within preceding 3 weeks from the first bexmarilimab administration
• Has untreated central nervous system (CNS) metastases and/or carcinomatous meningitis identified either on the baseline brain imaging obtained during the screening period. Subjects whose brain metastases have been treated may participate provided they show radiographic stability (defined as 2 brain images, both of which are obtained after treatment to the brain metastases. These imaging scans should both be obtained at least four weeks apart and show no evidence of intracranial progression). In addition, any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have returned to baseline or resolved. Any steroids administered as part of this therapy must be completed at least three days prior to study medication.
• Investigational therapy or major surgery within 4 weeks from the date of consent
• Active clinically serious infection \>grade 2 NCI-CTCAE version 5.0 (Appendix 6) within preceding 2 weeks from the date of consent
• Subject has not recovered from the previous therapies to Grade 1 severity as classified by the NCI-CTCAE version 5.0 (except Grade 2 alopecia, neuropathy or thyroid disorders)
• Pregnant or lactating women
• The subject requires systemic corticosteroid or other immunosuppressive treatment
• Use of live (attenuated) vaccines for 30 days prior to the start of study treatment, d during treatment, and until last visit
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Subject is unwilling or unable to comply with treatment and trial instructions
• Any condition that study investigators consider an impediment to safe trial participation
• Prior therapy for advanced stage or metastatic disease

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead
• Faron Pharmaceuticals Ltd: collaborator

Study Sites (1)

Mays Cancer Center, UT Health San Antonio

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

bexmarilimab; pembrolizumab

Condition Hierarchy (Ancestors)

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

Study Officials

• Supreet Kaur, MD

  UT Health San Antonio

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Dose levels will be escalated to determine maximum tolerated dose (MTD) in participants with non-small cell lung cancer (NSCLC) eligible for standard of care pembrolizumab treatment. MTD will be determined based on occurence of dose limiting toxicities (DLTs) by standard 3+3 escalation.

Study Record Dates

• First Submitted: December 10, 2021
• First Posted: December 28, 2021
• Study Start: June 1, 2023
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: July 20, 2023

Record last verified: 2023-07

Locations

US (1)