Clinical Trials /

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

NCT03881488

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: CTX-471-001
  • NCT ID: NCT03881488

Conditions

  • Locally Advanced Solid Tumor
  • Metastatic Cancer

Interventions

DrugSynonymsArms
CTX-471Part 1 Dose Escalation

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Part 1 Dose EscalationExperimentalEscalating doses of CTX-471 depending on cohort at enrollment.
  • CTX-471
Part 2 Dose ExpansionExperimentalDoses to be determined based on Part 1
  • CTX-471

Eligibility 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, 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 ≥ 1.5×10^9/L, platelet count of
             ≥100.0×10^9/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 creatinine clearance >60 mL/min 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 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 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. 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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)
Safety Issue:
Description:

Secondary Outcome Measures

Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description: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
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure:Overall Survival (OS)
Time Frame:From first dose of CTX-471 (Week 1 Day 1) until death (up to 2 years)
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Compass Therapeutics

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