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Study of CTX-471 in Patients Post PD-1/PD-L1 Inhibitors in Metastatic or Locally Advanced Malignancies

Sponsor
Compass Therapeutics (Industry)
Overall Status
Recruiting
CT.gov ID
NCT03881488
Collaborator
Iqvia Pty Ltd (Industry)
96
Enrollment
10
Locations
2
Arms
39.5
Anticipated Duration (Months)
9.6
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase 1, open-label, first-in-human study of CTX-471 monotherapy 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 parts: Part 1 Dose Escalation and Part 2 Dose Expansion.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
96 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1, Open-Label, Multiple-Ascending Dose Study of the Safety and Tolerability of CTX-471 in Patients With Inadequate Responses to PD-1/PD-L1 Checkpoint Inhibitors in Metastatic or Locally Advanced Malignancies
Actual Study Start Date :
May 17, 2019
Anticipated Primary Completion Date :
Jul 1, 2022
Anticipated Study Completion Date :
Sep 1, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Part 1 Dose Escalation

Escalating doses of CTX-471 depending on cohort at enrollment.

Drug: CTX-471
IV infusion every 2 weeks
Experimental: Part 2 Dose Expansion

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

Drug: CTX-471
IV infusion every 2 weeks

Outcome Measures

Primary Outcome Measures

  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)]

  2. Dose(s) of CTX 471 to be examined in Part 2 and the recommended Phase 2 dose(s) [From first dose of CTX-471 (Week 1 Day 1) until 60 days after the last CTX-471 injection (up to 2 years)]

Secondary Outcome Measures

  1. Maximum serum concentration (Cmax) of CTX-471 [From first dose of CTX-471 (Week 1 Day 1) until 60 days after the last CTX-471 injection (up to 2 years)]

  2. Area under the serum concentrations of CTX-471 versus time curve (AUC) [From first dose of CTX-471 (Week 1 Day 1) until 60 days after the last CTX-471 injection (up to 2 years)]

  3. Half-life (t1/2) of serum concentrations of CTX-471 [From first dose of CTX-471 (Week 1 Day 1) until 60 days after the last CTX-471 injection (up to 2 years)]

  4. Development of anti-drug antibodies (ADAs) and/or neutralizing antibodies of CTX-471 [From first dose of CTX-471 (Week 1 Day 1) until 60 days after the last CTX-471 injection (up to 2 years)]

  5. Objective Response Rate (ORR) (Percentage of Participants With Objective Response) as per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 [Baseline until confirmed disease progression (CR or PR) (up to 2 years)]

    ORR will be calculated as the number of participants with a confirmed complete response (CR) or a partial response (PR) divided by the number of participants dosed

  6. Duration of Response (DOR) as per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 [From the date of first confirmed CR or PR until the first date of recurrent or progressive disease (up to 2 years)]

  7. Progression-Free Survival (PFS) as per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 [From first dose of CTX-471 (Week 1 Day 1) until disease progression or death, whichever occur first (up to 2 years)]

  8. Overall Survival (OS) [From first dose of CTX-471 (Week 1 Day 1) until death (up to 2 years)]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  1. Age 18 years or older

  2. Histologically confirmed diagnosis of metastatic or locally advanced malignancies

  3. Measurable disease per RECIST 1.1

  4. 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

  5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1

  6. Life expectancy > 12 weeks

  7. Adequate bone marrow function defined by ANC of ≥ 1.5×109/L, platelet count of ≥100.0×109/L, and hemoglobin of ≥ 9.0 g/dL (with or without transfusion)

  8. Adequate hepatic function defined as serum total bilirubin < 2 mg/dL, AST/ALT ≤ 2.5 × ULN (or ≤ 5 × ULN in patients with liver metastases)

  9. Adequate renal function defined as serum creatinine < 1.5 × ULN or with normal serum creatinine levels defined as creatinine clearance > 60 mL/min as determined by the Cockcroft-Gault equation

  10. 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

  11. 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

  12. Last dose of previous PD-1 or PD-L1 therapy ≥ 28 days, other anticancer therapy > 21 days (or 2 half-lives for proteins, whichever is longer), radiotherapy > 21 days (concurrent localized palliative radiotherapy is allowed during CTX-471 treatment), or surgical intervention >21 days prior to the first dose of CTX-471

  13. Resolution of all prior anti-cancer therapy toxicities ≤ Grade 1

  14. Willingness to provide pre- and post-treatment fresh tumor biopsies

  15. Capable of understanding and complying with protocol requirements

  16. Signed and dated institutional review board/independent ethics committee-approved informed consent form before any protocol-directed screening procedures are performed

Exclusion Criteria:

  1. Developed clinically significant adverse reaction to PD-1 or PD-L1 therapy, including immune related adverse reactions, which led to discontinuation of treatment

  2. Prior treatment with other investigational immune-oncology therapies

  3. 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

  4. Patient is a pregnant or lactating WCBP

  5. Prior organ transplantation

  6. Active hepatitis B virus, hepatitis C virus, or human immunodeficiency virus infection or a positive serological test at Screening within 28 days of dosing with CTX 471

  7. 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

  8. History of central nervous system metastases

  9. History of seizure disorders

  10. Congestive heart failure (> New York Heart Association Class II), active coronary artery disease, unevaluated new onset angina within 3 months or unstable angina (angina symptoms at rest) or clinically significant cardiac arrhythmias

  11. Other systemic conditions or organ abnormalities that in the opinion of the Investigator may interfere with the conduct and/or interpretation of the current study

Contacts and Locations

Locations

Site City State Country Postal Code
1 Ocala Oncology Center Ocala Florida United States 34474
2 Hematology Oncology Associates Of The Treasure Coast Port Saint Lucie Florida United States 34952
3 Massachusetts General Hospital Boston Massachusetts United States 02114
4 Dana-Farber Cancer Institute Boston Massachusetts United States 02215
5 Washington University School of Medicine, Siteman Cancer Center Saint Louis Missouri United States 63110
6 Hackensack University Medical Center Hackensack New Jersey United States 07601
7 Mt Sinai New York New York United States 10029
8 Duke University School of Medicine Durham North Carolina United States 27705
9 Institute for Translational Oncology Research (ITOR) Greenville South Carolina United States 29605
10 Mary Crowley Cancer Research Dallas Texas United States 75251

Sponsors and Collaborators

  • Compass Therapeutics
  • Iqvia Pty Ltd

Investigators

  • Study Director: Thomas Scheutz, MD, PhD, Compass Therapeutics

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Compass Therapeutics
ClinicalTrials.gov Identifier:
NCT03881488
Other Study ID Numbers:
  • CTX-471-001
First Posted:
Mar 19, 2019
Last Update Posted:
Sep 30, 2021
Last Verified:
Sep 1, 2021
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Neoplasm Metastasis

Study Results

No Results Posted as of Sep 30, 2021