IRB Study Number 23-1060
Status Recruiting
Institute Taussig Cancer Institute
Description
Primary Objectives
To investigate the safety of monotherapy and T- Plex combination TCR-Ts
To determine the recommended phase 2 dose of monotherapy and T- Plex combination TCR-Ts
Secondary Objectives
To investigate preliminary anti-tumor activity of monotherapy and T- Plex combination TCR-Ts
To investigate the feasibility of repeat dosing of monotherapy and T- Plex combination TCR-Ts
Inclusion Criteria
Be at least 18 years of age inclusive at the time of signing the informed consent.
Have a locally advanced (unresectable) or metastatic solid tumor for which there are no acceptable available treatment options, after failure of the standard of care systemic therapies used for the treatment of locally advanced, unresectable, or metastatic disease for that particular indication. Specifically:
• must be considered ineligible, refractory to, or have declined FDA-approved checkpoint immunotherapy drugs such as PD1, PD-L1, LAG-3 and CTLA4 antibodies, if relevant for their tumor type
• must be considered ineligible, refractory to, or have declined any FDA-approved molecularly targeted therapies for their tumor type, including but not limited to, EGFR, ALK, ROS-1, NTRK, MET, RET, KRAS, BRAF/MEK, or PARP inhibitors and antibody-drug conjugates.
Have completed screening on Study TSCAN-003 and been notified by the Sponsor that they may be eligible for TSCAN-002 based on HLA, TAA and LOH results.
Have Eastern Cooperative Oncology Group (ECOG) Performance status 0-1.
Have understood and signed the informed consent form; decision-impaired adults may consent with their legally authorized representative.
Have at least 1 measurable lesion per modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Have adequate bone marrow function evidenced by:
• Absolute neutrophil count (ANC) ≥ 1000/μL
• Platelet count ≥ 75,000/μL
• Hemoglobin > 8 g/dL
The administration of blood products and/or growth factors to participants recovering from recent myelosuppressive therapy is permitted prior to leukapheresis; however, these blood cell counts must be maintained independent of blood products and growth factors prior to initiating lymphodepleting chemotherapy (see Section 6.2.1).
- Have adequate renal, hepatic, cardiac and pulmonary function as evidenced by:
• Measured or estimated creatinine clearance ≥50 mL/min, determined using a standard tool for calculation (e.g., CKD-EPI, Modified Diet in Renal Disease, or Cockcroft Gault equations, etc)
• Alanine transaminase/Aspartate aminotransferase (ALT/AST) ≤ 2.5 x upper limit of normal (ULN) or ≤ 5 x ULN if documented liver metastases
• Bilirubin ≤ 1.5 x ULN (unless participant has documented Gilbert’s syndrome with direct bilirubin <35% of total bilirubin)
• Serum albumin ≥ 2.5 g/dL without evidence of anasarca
• Left ventricular ejection fraction (LVEF) by ECHO or MUGA ≥50%
• No pleural effusion requiring thoracentesis within 14 days prior to enrollment
• Oxygen saturation ≥ 90% on room air
- If female, must not be pregnant nor breast feeding and at least one of the following conditions must apply:
• Not a woman of childbearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant.
• Agrees to follow contraceptive guidance from the start of lymphodepleting chemotherapy (14 days earlier if using oral contraceptives) until at least 12 months after the last dose of cyclophosphamide.
- If male, must agree to follow contraceptive guidance and to not donate/bank sperm from the start of lymphodepleting chemotherapy until at least 6 months after the last dose of investigational product.
Exclusion Criteria
Have medical, psychological, or social conditions that would make the participant an unsuitable candidate for a Phase 1 cell therapy study, at the discretion of the Investigator or Sponsor.
Have a history of myocardial infarction, cardiac angioplasty or stenting, unstable angina, cardiac arrhythmia requiring antiarrhythmic or procedure, or other clinically significant cardiac disease within 6 months prior to enrollment
Have a history of stroke or transient ischemic attack within 6 months prior to enrollment
Have received systemic corticosteroid therapy >10 mg of prednisone daily or equivalent within 7 days prior to enrollment
Have a history of severe hypersensitivity to fludarabine, cyclophosphamide, or investigational product excipients, including human serum albumin, Cryostor (DMSO or Dextran 40), or Plasma-Lyte.
Have untreated or symptomatic central nervous system (CNS) metastases or cytology proven carcinomatous meningitis.
• Participants who have undergone treatment directed at CNS metastases must have post-treatment imaging documenting stabilization or improvement ≥ 4 weeks after that treatment and must be asymptomatic with stable or decreasing steroid requirement that does not exceed 10 mg prednisone or equivalent daily.
• Participants with small (e.g., <1 cm diameter), asymptomatic CNS metastases that do not require treatment, have been stable for ≥4 weeks, and do not show evidence of hemorrhage are permitted to enroll, following approval by the Sponsor Medical Monitor.
- Concurrently receive another anti-cancer therapy. Prior therapies must wash out for the shorter of 5 half-lives or the following durations before enrollment:
• Cytotoxic chemotherapy – 2 weeks
• Tyrosine kinase/small molecule inhibitor – 2 weeks
• Systemically administered Biologic therapy/monoclonal antibody – 4 weeks
• Radiation therapy – if dose <30 Gy (Gray) – 2 days, if dose >30Gy – 2weeks
• Locally administered therapies – 2 days
• Participants must have recovered from treatment related toxicities to Grade ≤1 or baseline
- Have an acute fungal, bacterial, or viral infection requiring systemic anti-microbials for management.
• Participants with known HIV-positivity must have undetectable viral load and be on a stable anti-retroviral regimen for ≥ 4 weeks.
- Have had another malignancy, unless disease free for ≥5 years.
• Participants with non-melanoma skin cancers, carcinomas in situ, or cervical intraepithelial neoplasia are eligible if definitive treatment has been completed.
• Participants with organ-confined prostate cancer with no evidence of recurrent or progressive disease are eligible if hormonal therapy has been initiated or if the malignancy has been surgically removed or treated with definitive radiotherapy.
• Participants with thyroid or testicular cancers are eligible if they have not had metastatic disease and definitive treatment has been completed.
