About the study

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.

Who can take part?

You may be eligible to participate in the study if you meet the following 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, 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 ≥ 1.5×10^9/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 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
15. and post-treatment fresh tumor biopsies
16. Capable of understanding and complying with protocol requirements
17. 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

For a full list of inclusion/exclusion criteria, please visit ClinicalTrials.gov

Study locations

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How to apply

Determine if a study site for this clinical trial is near you. Contact the study to apply.