FT836 With or Without Chemotherapy and/or Monoclonal Antibodies, in Participants With Advanced Solid Tumors

Official title

A Phase 1, Open-Label Study of FT836, an Off-the-Shelf CAR T-Cell Therapy, With or Without Chemotherapy and/or Monoclonal Antibodies, in Participants With Advanced Solid Tumors

Overview

This is a phase 1 study of FT836 administered in participants with advanced solid tumors. The primary objectives of the study are to evaluate the safety and tolerability of FT836 with or without paclitaxel and/or trastuzumab or cetuximab, and to determine the recommended phase 2 dose (RP2D) of FT836 in combination with trastuzumab or cetuximab; each objective will be assessed with or without paclitaxel chemotherapy.

Interventions

• Drug FT836
  FT836 drug product is administered as an intravenous infusion on multiple days schedule at treatment cycle.
• Drug Paclitaxel
  IV infusion ; 80 mg/m2 QW; Days -21, -14, and -7
• Drug Cetuximab
  Cetuximab administration will begin on Day -4 at the recommended initial dose of 400 mg/m2 as a 120-minute IV infusion
• Drug Trastuzumab
  trastuzumab administration will begin on Day -4 at an initial dose of 4 mg/kg as a 90-minute IV infusion.

Primary outcome measures

• Number of participants with dose limiting toxicities (DLTs) [Time frame: From Day 1 through Day 29 of Cycle 1( each cycle is 56 days)]
• Severity of DLTs [Time frame: From Day 1 through Day 29 of Cycle 1( each cycle is 56 days)]

Secondary outcome measures (4)

• Overall Response Rate (ORR) [Time frame: Up to approximately 24 months]
• Duration of Response (DOR) [Time frame: Up to approximately 24 months]
• Progression-Free Survival (PFS) [Time frame: Up to approximately 24 months]
• Overall Survival (OS) [Time frame: Up to approximately 24 months]

Eligibility criteria

Inclusion criteria

• For all regimens, disease that is not amenable to curative therapy and that has relapsed or progressed following at least one line of prior systemic therapy.
• Evidence of adequate organ function as determined by all of the following:

• Absolute neutrophil count (ANC) >1000/µL without growth factor support within 7 days prior to start of first study intervention
• Platelet count ≥75,000/µL without transfusion support within 14 days prior to start of first study intervention
• Estimated creatinine clearance ≥50 mL/minute by Cockcroft-Gault method or other standard institutional method
• Total bilirubin ≤1.5 × upper limit of normal (ULN); for participants with documented Gilbert syndrome, total bilirubin must be ≤3 ×ULN
• Aspartate transaminase (AST) ≤3 × ULN or alanine transaminase (ALT) ≤3 × ULN; in participants with documented liver metastases, AST or ALT ≤5 × ULN
• Alkaline phosphatase (ALP) ≤2.5 × ULN; in participants with documented liver or bone metastases, ALP ≤5 × ULN
• Oxygen saturation >90% on room air
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.
• Presence of measurable disease by RECIST, v1.1 assessed within 28 days prior to start of first study intervention.
• Presence of baseline safely accessible lesions of adequate size for on-treatment biopsies (exceptions for lesion size may be granted with medical monitor approval) and participant willingness to undergo protocol prescribed on-treatment biopsies.

Exclusion criteria

• Clinically significant cardiovascular disease including any of the following: uncontrolled/ unstable cardiac arrhythmias, myocardial infarction within 6 months prior to start of first study intervention, unstable angina or congestive heart failure of New York Heart Association (NYHA) Grade 2 or higher, or cardiac ejection fraction <50%.
• Receipt of any biological therapy, chemotherapy, investigational therapy, or radiation therapy within 2 weeks or five half-lives prior to start of fifirst study intervention, whichever is shorter.
• Known active central nervous system (CNS) involvement by malignancy. Participants with prior CNS involvement from their malignancy must have completed effective treatment of their CNS disease with no symptoms of disease in the absence of steroid treatment and at least stable findings on relevant CNS imaging and no evidence of leptomeningeal disease for at least 4 weeks prior to study enrollment.
• Non-malignant CNS disease such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease or receipt of medications for these conditions within 6 months prior to study enrollment.
• Currently receiving or likely to require systemic immunosuppressive therapy (e.g., prednisone ≥5 mg daily) for any reason from start of first study intervention to Day 29 with the exception of corticosteroids as a premedication for chemotherapy side effects per institutional standard of care or as mandated by the protocol.
• Any history of Grade ≥3 immune-related AE or Grade ≥2 eye toxicity attributed to prior cancer immunotherapy, other than endocrinopathy managed with replacement therapy or asymptomatic elevation of serum amylase or lipase.
• Grade ≥2 peripheral neuropathy limiting instrumental activities of daily living.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 5 centers

• University of Southern California — La Jolla
• UC San Diego Moores Cancer Center — La Jolla
• University of Minnesota Masonic Cancer Center — Minneapolis
• Thomas Jefferson University, Sidney Kimmel Cancer Center — Philadelphia
• M. D. Anderson Cancer Center — Houston

Identifiers

NCT: NCT07216105 · FT836-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗