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Study of CTX-471 in Patients With Inadequate Responses to PD-1/PD-L1 Checkpoint Inhibitors in Metastatic or Locally Advanced Malignancies

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ClinicalTrials.gov Identifier: NCT03881488
Recruitment Status : Not yet recruiting
First Posted : March 19, 2019
Last Update Posted : March 19, 2019
Sponsor:
Collaborator:
IQVIA
Information provided by (Responsible Party):
Compass Therapeutics

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
Locally Advanced Malignant Neoplasm Metastatic Neoplasm Drug: CTX-471 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 81 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
Estimated Study Start Date : April 2019
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : July 2021

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
Doses to be determined based on Part 1
Drug: CTX-471
IV infusion every 2 weeks




Primary Outcome Measures :
  1. Number of participants with dose limiting toxicities (DLTs), treatment-emergent adverse events (TEAEs), and/or changes in clinical laboratory abnormalities [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: From first dose of CTX-471 (Week 1 Day 1) until death (up to 2 years) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  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 creatinine clearance >60 mL/min for patients with creatinine levels above institutional normal (as determined by 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 3 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
  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 immune-oncology therapies (e.g. oncolytic virus, cellular therapies); prior ipilimumab is allowed
  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. History of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus infection or a positive serological test at Screening within 7 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 or current 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. Clinically significant baseline QT interval corrected with Fridericia's method (QTcF), including QTcF > 480 msec
  12. 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03881488


Contacts
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Contact: Nora Zizlsperger, PhD 617-500-8099 ext 118 nora.zizlsperger@compasstherapeutics.com
Contact: Yu Liu, MD, PhD, MBA yu.liu@compasstherapeutics.com

Sponsors and Collaborators
Compass Therapeutics
IQVIA
Investigators
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Principal Investigator: Matthew Galsky, MD Mt. Sinai in New York (Ichan School of Medicine)
Principal Investigator: Martin Gutierrez, MD Hackensack University John Theurer Cancer Center
Principal Investigator: William Edenfield, MD Institute for Translational Oncology Research (ITOR)
Principal Investigator: Tanner Johanns, MD Washington University Siteman Cancer Center
Principal Investigator: Minal Barve, MD Mary Crowley Cancer Research Center

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Responsible Party: Compass Therapeutics
ClinicalTrials.gov Identifier: NCT03881488     History of Changes
Other Study ID Numbers: CTX-471-001
First Posted: March 19, 2019    Key Record Dates
Last Update Posted: March 19, 2019
Last Verified: March 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Neoplasms
Neoplasm Metastasis
Neoplastic Processes
Pathologic Processes