Study of CTX-471 as a Monotherapy or in Combination With Pembrolizumab in Patients Post PD-1/PD-L1 Inhibitors in Metastatic or Locally Advanced Malignancies

NCT03881488 | Completed Phase 1 FDA Drug

• 3 other identifiers: CTX-471-001KEYNOTE-E65MK-3475-E65
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 10

Brief Summary

This is a Phase 1, open-label, first-in-human study of CTX-471 administered as a monotherapy or in combination with pembrolizumab in patients with metastatic or locally advanced malignancies that have progressed while receiving an approved PD-1 or PD-L1 inhibitor. The study will be conducted in 2 treatment arms (Monotherapy Arm 1 and Combination Arm 2). Each arm will have two parts: Part 1 Dose Escalation and Part 2 Dose Expansion.

Conditions

Locally Advanced Solid Tumor; Metastatic Cancer; Non-small Cell Lung Cancer; Small Cell Lung Cancer; Mesothelioma; Melanoma; Head and Neck Cancer

Outcome Measures

Primary Outcomes (1)

• Number of participants with dose limiting toxicities (DLTs), treatment-emergent adverse events (TEAEs), and/or changes in clinical laboratory abnormalities

  From first dose of CTX-471 (Week 1 Day 1) until 60 days after the last CTX-471 injection (up to 2 years)

Secondary Outcomes (8)

• Maximum serum concentration (Cmax) of CTX-471 as a monotherapy and CTX-471 in combination with pembrolizumab

  From first dose of CTX-471 (Week 1 Day 1) until 60 days after the last CTX-471 injection (up to 2 years)

• Area under the serum concentrations of CTX-471 versus time curve (AUC) for CTX-471 as a monotherapy and CTX-471 in combination with pembrolizumab

  From first dose of CTX-471 (Week 1 Day 1) until 60 days after the last CTX-471 injection (up to 2 years)

• Half-life (t1/2) of serum concentrations of CTX-471 as a monotherapy and CTX-471 in combination with pembrolizumab

  From first dose of CTX-471 (Week 1 Day 1) until 60 days after the last CTX-471 injection (up to 2 years)

• Development of anti-drug antibodies (ADAs) and/or neutralizing antibodies of CTX-471 as a monotherapy and CTX-471 in combination with pembrolizumab

  From first dose of CTX-471 (Week 1 Day 1) until 60 days after the last CTX-471 injection (up to 2 years)

• Objective Response Rate (ORR) (Percentage of Participants With Objective Response) as per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 of CTX-471 as a monotherapy and CTX-471 in combination with pembrolizumab

  Baseline until confirmed disease progression (CR or PR) (up to 2 years)

Study Arms (4)

Arm 1 Part 1 Dose Escalation

EXPERIMENTAL

Escalating doses of CTX-471 depending on cohort at enrollment

Drug: CTX-471

Arm 1 Part 2 Dose Expansion

EXPERIMENTAL

Two dose groups of CTX-471 (0.3 mg/kg and 0.6 mg/kg)

Drug: CTX-471

Arm 2 Part 1 Dose Escalation

EXPERIMENTAL

Escalating doses of CTX-471 in combination with pembrolizumab (KEYTRUDA® ) depending on cohort at enrollment

Drug: CTX-471; Drug: Pembrolizumab (KEYTRUDA®)

Arm 2 Part 2 Dose Expansion

EXPERIMENTAL

Two cohorts of CTX-471 (0.3 mg/kg and 0.6 mg/kg) in combination with pembrolizumab (KEYTRUDA® ) (400 mg) in three tumor type subgroups. Cohort 1 - Group 1A - NSCLC , Group 1B -SCLC and Group 1C - Melanoma. Cohort 2 Group 2A - NSCLC, Group 2B - SCLC and Group 2C -Melanoma.

Drug: CTX-471; Drug: Pembrolizumab (KEYTRUDA®)

Interventions

CTX-471 DRUG

IV infusion every 2 weeks

Arm 1 Part 1 Dose Escalation; Arm 1 Part 2 Dose Expansion; Arm 2 Part 1 Dose Escalation; Arm 2 Part 2 Dose Expansion

Pembrolizumab (KEYTRUDA®) DRUG

IV infusion every 6 weeks

Also known as: KEYTRUDA®

Arm 2 Part 1 Dose Escalation; Arm 2 Part 2 Dose Expansion

Eligibility Criteria

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

You may qualify if:

• Age 18 years or older
• Histologically confirmed diagnosis:
• Monotherapy Arm 1 ( Part 1 and 2): metastatic or locally advanced malignancies
• Combination Arm 2 Par 1 Dose Escalation: metastatic or locally advanced non-small cell lung, small cell lung cancer, mesothelioma, melanoma, or head and neck cancer
• Combination Arm 2 Part 2 Dose Expansion: metastatic or locally advanced non-small cell lung, small cell lung cancer, or melanoma
• Measurable disease per RECIST 1.1
• Disease progression after at least 12 weeks and at least 2 doses of a commercially available PD-1 or PD-L1 inhibitor per approved prescriber's information, whether monotherapy or in combination therapy, with no other intervening systemic anticancer therapy prior to enrollment
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Life expectancy \> 12 weeks
• Adequate bone marrow function defined by ANC of ≥ 1.5×10\^9/L, platelet count of ≥100.0×10\^9/L, and hemoglobin of ≥ 9.0 g/dL (with or without transfusion)
• a. For Combination Arm 2: these criteria must be met without packed red blood cell (pRBC) transfusion within the prior 2 weeks. Patients can be on a stable dose of erythropoietin (≥ approximately 3 months)
• Adequate hepatic function defined as serum total bilirubin \< 1.5 ULN, AST/ALT ≤ 2.5 × ULN (or ≤ 5 × ULN in patients with liver metastases)
• Adequate renal function defined as creatinine clearance \> 30 mL/min as determined by the Cockcroft-Gault equation
• Female patients must be surgically sterile (or have a monogamous partner who is surgically sterile) or be least 2 years postmenopausal or commits to use 2 acceptable forms of birth control (defined as the use of an intrauterine device, a barrier method with spermicide, condoms, any form of hormonal contraceptives, or abstinence) for the duration of the study and for 4 months following the last dose of study treatment. Male patients must be sterile (biologically or surgically) or commit to the use of a reliable method of birth control (condoms with spermicide) for the duration of the study and for 4 months following the last dose of study treatment
• Female patients who are women of childbearing potential (WCBP) must have a negative serum pregnancy test at Screening within 7 days of dosing with CTX-471 for Monotherapy Arm 1, and within 72 hours of dosing with CTX-471 and pembrolizumab for Combination Arm 2

You may not qualify if:

• Developed clinically significant adverse reaction to PD-1 or PD-L1 therapy, including immune related adverse reactions, which led to discontinuation of treatment
• Prior treatment with other investigational immune-oncology therapies
• Systemic therapy with immunosuppressive agents within 7 days before the start of CTX-471 treatment. Topical, intranasal, intraocular, or inhaled corticosteroids and physiologic replacement for patients with adrenal insufficiency are allowed
• Patient is a pregnant or lactating WCBP
• Prior solid organ transplantation
• Active hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus infection (HIV) or a positive serological test at Screening within 28 days of dosing with CTX 471
• Participants who are HBsAg (hepatitis B surface antigen) positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization Note: Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention
• Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening Note: Participants must have completed curative anti-viral therapy at least 4 weeks prior to randomization
• HIV infected participants must be on anti-retroviral therapy (ART) and have a well-controlled HIV infection/disease defined as:
• Participants on ART must have a CD4+ T-cell count \>350 cells/mm3 at time of screening
• Participants on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 copies/mL or the lower limit of qualification (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks prior to screening
• Participants on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks prior to study entry (Day 1)
• Active autoimmune disease or medical conditions requiring chronic steroid (ie, \> 10 mg/day prednisone or equivalent) or immunosuppressive therapy. Patients with a prior history of autoimmune disease may be eligible following discussion with the Medical Monitor
• For Monotherapy Arm 1 Only: History of central nervous system metastases
• History of seizure disorders

Sponsors & Collaborators

• Compass Therapeutics: lead
• IQVIA Pty Ltd: collaborator
• Merck, Sharp & Dohme, LLC, Rahway, NJ USA: collaborator

Study Sites (10)

Ocala Oncology Center

Ocala, Florida, 34474, United States

Location

Hematology Oncology Associates Of The Treasure Coast

Port Saint Lucie, Florida, 34952, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Washington University School of Medicine, Siteman Cancer Center

St Louis, Missouri, 63110, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Mt Sinai

New York, New York, 10029, United States

Location

Duke University School of Medicine

Durham, North Carolina, 27705, United States

Location

Institute for Translational Oncology Research (ITOR)

Greenville, South Carolina, 29605, United States

Location

Mary Crowley Cancer Research

Dallas, Texas, 75251, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Carcinoma, Non-Small-Cell Lung; Small Cell Lung Carcinoma; Mesothelioma; Melanoma; Head and Neck Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Mesothelial; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Thomas Scheutz, MD, PhD

  Compass Therapeutics

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: March 13, 2019
• First Posted: March 19, 2019
• Study Start: May 17, 2019
• Primary Completion: May 21, 2025
• Study Completion: May 21, 2025
• Last Updated: April 17, 2026

Record last verified: 2025-06

Locations

US (10)