Phase I/II Study of Autologous T Cells to Express T-Cell Receptors (TCRs) in Subjects With Solid Tumors

Brief summary public domain (ClinicalTrials.gov)

A Phase I/II study of autologous T cells engineered using the Sleeping Beauty transposon/transposase system to express TCR(s) reactive against neoantigens in subjects with relapsed/refractory solid tumors

Detailed description public domain (ClinicalTrials.gov)

A Phase I/II study of autologous T cells engineered using the Sleeping Beauty transposon/transposase system to express TCR(s) reactive against neoantigens in subjects with relapsed/refractory solid tumors. An HLA Typing and Tumor Neoantigen Mutation Testing Protocol (Protocol # TCR001-002) has been used to identify patients for potential enrollment into this Study Protocol. Subjects who have completed the HLA Typing and Tumor Neoantigen Mutation Testing Protocol, i.e., subjects for whom a TCR matching the subject's somatic mutation(s) and HLA type restriction combination is available in Alaunos' TCR library will be eligible for enrollment on this study. The Phase I part of this study is a prospective, open-label, dose-escalation study of TCR-T cell drug product in patients with progressive or recurrent solid tumors who have failed standard therapy. The Phase II part is a prospective, open-label, single dose portion of the study. The Phase II part will begin once the MTD/RP2D in the Phase I part has been determined. Subjects with one of the following histologically confirmed solid tumors will be included: * Cohort 1: Gynecologic cancer (e.g., ovarian, endometrial) * Cohort 2: Colorectal cancer * Cohort 3: Pancreatic cancer * Cohort 4: Non-small cell lung cancer (NSCLC); NSCLC includes but is not limited to squamous cell carcinoma, adenosquamous carcinoma or adenocarcinomas * Cohort 5: Cholangiocarcinoma Subject must have a tumor mutation and HLA typing combination that matches to at least one of the following TCRs in the Alaunos' library (mutation \& HLA type): * KRAS G12D \& HLA-A\*11:01 * KRAS G12D \& HLA-C\*08:02 * KRAS G12V \& HLA-A\*11:01 * KRAS G12V \& HLA-C\*01:02 * TP53 R175H \& HLA-A\*02:01 * TP53 R175H \& HLA-DRB1\*13:01 * TP53 R248W \& HLA-A\*68:01 * TP53 Y220C \& HLA-A\*02:01 * TP53 Y220C \& HLA-DRB3\*02:02 * EGFR E746-A750del \& HLA-DPA1\*02:01, DPB1\*01:01

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Number of Participants With Treatment-Emergent Adverse Events [From initiation of lymphodepletion through Day 28 after TCR-T cell infusion, and through long-term follow-up for up to 1 year.]. Number, participants. Any TEAE: Assigned Dose Level 1 (Target 5 × 10⁹ TCR+ Cells) (n=1): 1; Assigned Dose Level 2 (Target 40 × 10⁹ TCR+ Cells) (n=7): 7. Drug-related TEAE: Assigned Dose Level 1 (Target 5 × 10⁹ TCR+ Cells) (n=1): 1; Assigned Dose Level 2 (Target 40 × 10⁹ TCR+ Cells) (n=7): 7. Drug-related Grade 3 or higher TEAE: Assigned Dose Level 1 (Target 5 × 10⁹ TCR+ Cells) (n=1): 1; Assigned Dose Level 2 (Target 40 × 10⁹ TCR+ Cells) (n=7): 6. TEAE leading to death: Assigned Dose Level 1 (Target 5 × 10⁹ TCR+ Cells) (n=1): 0; Assigned Dose Level 2 (Target 40 × 10⁹ TCR+ Cells) (n=7): 0. Treatment-emergent SAE: Assigned Dose Level 1 (Target 5 × 10⁹ TCR+ Cells) (n=1): 1; Assigned Dose Level 2 (Target 40 × 10⁹ TCR+ Cells) (n=7): 2.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Frequency of Dose Limiting Toxicities [From Day 0 to Day 28 post TCR-T cell drug product infusion.]. Count Of Participants, Participants. Assigned Dose Level 1 (Target 5 × 10⁹ TCR+ Cells) (n=1): 0; Assigned Dose Level 2 (Target 40 × 10⁹ TCR+ Cells) (n=7): 0.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Determination of Maximum Tolerated Dose (MTD) or Recommended Phase II Dose (RP2D) [From Day 0 to Day 28 post TCR-T cell drug product infusion.]. Number, Dose level of TCR-T cells infused. All Dose Levels (DLT-Evaluable Population) (n=8): NA [The MTD or RP2D could not be determined because the study closed early before sufficient participants were treated and evaluated for DLTs to allow formal determination.].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Feasibility of TCR-T Cell Drug Product Manufacturing [From apheresis collection to the release of the final TCR-T cell drug product for infusion, estimated to be approximately 5 weeks]. Number, participants. Unable to be apheresed for logistical or medical reasons: Apheresed Participants (Feasibility Population) (n=14): 0. Apheresis performed but manufacturing not initiated due to study closure: Apheresed Participants (Feasibility Population) (n=14): 2. Product was successfully manufactured but not administered due to progression or comorbidity.: Apheresed Participants (Feasibility Population) (n=14): 2. Infused successfully at the planned dose after 1 manufacturing round.: Apheresed Participants (Feasibility Population) (n=14): 6. Infused at a lower dose than planned after 1 manufacturing round.: Apheresed Participants (Feasibility Population) (n=14): 1. Infused at a lower dose than planned after 2 manufacturing rounds.: Apheresed Participants (Feasibility Population) (n=14): 1. Patients who were manufacturing failures after 2 manufacturing rounds.: Apheresed Participants (Feasibility Population) (n=14): 1. Product was successfully manufactured but not administered due to study closure.: Apheresed Participants (Feasibility Population) (n=14): 1.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

TCR-T Cell Persistence [Baseline through Month 18 post-infusion.]. Median, copies/1x10^6 cells (Full Range). Baseline (1 week prior to infusion): Assigned Dose Level 1 (Target 5 × 10⁹ TCR+ Cells) (n=1): NA [Values listed as "Not Detected (ND)" or "Below the Limit of Quantitation (BLOQ)" could not be quantified by the qPCR assay and are therefore reported as NA.]; Assigned Dose Level 2 (Target 40 × 10⁹ TCR+ Cells) (n=7): NA (0 to 0) [Values listed as "Not Detected (ND)" or "Below the Limit of Quantitation (BLOQ)" could not be quantified by the qPCR assay and are therefore reported as NA.]. Predose Day 0: Assigned Dose Level 1 (Target 5 × 10⁹ TCR+ Cells) (n=1): NA [Values listed as "Not Detected (ND)" or "Below the Limit of Quantitation (BLOQ)" could not be quantified by the qPCR assay and are therefore reported as NA.]; Assigned Dose Level 2 (Target 40 × 10⁹ TCR+ Cells) (n=7): NA (0 to 0) [Values listed as "Not Detected (ND)" or "Below the Limit of Quantitation (BLOQ)" could not be quantified by the qPCR assay and are therefore reported as NA.]. Post Dose Day 0: Assigned Dose Level 1 (Target 5 × 10⁹ TCR+ Cells) (n=1): 4,240,000; Assigned Dose Level 2 (Target 40 × 10⁹ TCR+ Cells) (n=7): 2,570,000 (779,000 to 3,970,000). Day 1: Assigned Dose Level 1 (Target 5 × 10⁹ TCR+ Cells) (n=1): 3,190,000; Assigned Dose Level 2 (Target 40 × 10⁹ TCR+ Cells) (n=7): 59,200 (20,700 to 1,710,000). Day 2: Assigned Dose Level 1 (Target 5 × 10⁹ TCR+ Cells) (n=1): 2,640,000; Assigned Dose Level 2 (Target 40 × 10⁹ TCR+ Cells) (n=7): 408,000 (0 to 2,270,000). Day 4: Assigned Dose Level 1 (Target 5 × 10⁹ TCR+ Cells) (n=1): 3,500,000; Assigned Dose Level 2 (Target 40 × 10⁹ TCR+ Cells) (n=7): 570,000 (18,700 to 3,400,000). Day 7: Assigned Dose Level 1 (Target 5 × 10⁹ TCR+ Cells) (n=1): 743,000; Assigned Dose Level 2 (Target 40 × 10⁹ TCR+ Cells) (n=7): 101,000 (5,320 to 3,730,000). Day 10: Assigned Dose Level 1 (Target 5 × 10⁹ TCR+ Cells) (n=1): 674,000; Assigned Dose Level 2 (Target 40 × 10⁹ TCR+ Cells) (n=7): 112,000 (14,200 to 961,000). Day 14: Assigned Dose Level 1 (Target 5 × 10⁹ TCR+ Cells) (n=1): 984,000; Assigned Dose Level 2 (Target 40 × 10⁹ TCR+ Cells) (n=7): 112,000 (7,900 to 938,000). Day 21: Assigned Dose Level 1 (Target 5 × 10⁹ TCR+ Cells) (n=1): 504,000; Assigned Dose Level 2 (Target 40 × 10⁹ TCR+ Cells) (n=7): 41,300 (1,140 to 489,000). Day 28: Assigned Dose Level 1 (Target 5 × 10⁹ TCR+ Cells) (n=1): 404,000; Assigned Dose Level 2 (Target 40 × 10⁹ TCR+ Cells) (n=7): 32,100 (0 to 297,000). Week 6: Assigned Dose Level 1 (Target 5 × 10⁹ TCR+ Cells) (n=1): 197,000; Assigned Dose Level 2 (Target 40 × 10⁹ TCR+ Cells) (n=7): 27,800 (0 to 203,000). Week 12: Assigned Dose Level 1 (Target 5 × 10⁹ TCR+ Cells) (n=1): 163,000; Assigned Dose Level 2 (Target 40 × 10⁹ TCR+ Cells) (n=7): 27,200 (1,960 to 121,000). Month 3: Assigned Dose Level 2 (Target 40 × 10⁹ TCR+ Cells) (n=7): 42,400. Month 6: Assigned Dose Level 1 (Target 5 × 10⁹ TCR+ Cells) (n=1): 88,100; Assigned Dose Le

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Percent Change in TCR-T Cell Count From Post Dose to Day 28 [Post-dose through Day 28]. Median, percent change from peak post dose (Full Range). Assigned Dose Level 1 (Target 5 × 10⁹ TCR+ Cells) (n=1): -90.5; Assigned Dose Level 2 (Target 40 × 10⁹ TCR+ Cells) (n=7): -96.7 (-100 to -91.1).