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

The MTD and/or RP2D was to be determined based on dose-limiting toxicities observed during the dose-escalation phase. The planned definition required ≥2 patients at a given dose level to experience a DLT to declare that dose not tolerated.

Time frame: From Day 0 to Day 28 post TCR-T cell drug product infusion.

Population: All participants who received a TCR-T infusion and were monitored for DLTs were included in a single analysis population. Eight participants were infused (6 at Dose Level 1, 2 at Dose Level 2). The MTD/RP2D could not be determined because the study closed early before enough evaluable participants were treated to allow formal determination.

Number of participants experiencing DLTs, defined as specific adverse events attributable to the TCR-T cell drug product occurring within the first 28 days of infusion. DLTs include, but are not limited to, Grade 4 neutropenia lasting ≥ 14 days, Grade 4 thrombocytopenia, Grade 3 thrombocytopenia with significant bleeding, and ≥ Grade 3 febrile neutropenia with hemodynamic compromise. Non-hematologic DLTs include Grade 3 or 4 Cytokine Release Syndrome (CRS) that does not improve to Grade ≤ 2 within 72 hours, and Grade 3 Immune-effector cell-associated neurotoxicity syndrome (ICANS) that does not resolve to Grade ≤ 2 within 7 days, among others. The severity of adverse events will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.

Time frame: From Day 0 to Day 28 post TCR-T cell drug product infusion.

Population: Participants who received the planned TCR-T cell infusion and either experienced a DLT or completed the 28-day DLT observation period; those with major protocol deviations unrelated to safety during this period were considered non-evaluable.

Treatment-emergent adverse events (TEAEs) were defined as any adverse event that began or worsened after initiation of lymphodepletion and up to 28 days following TCR-T cell infusion. TEAEs were coded using MedDRA and summarized by system organ class and preferred term, severity, and relationship to study treatment. Participants were followed for delayed or ongoing toxicities for up to 1 year.

Time frame: From initiation of lymphodepletion through Day 28 after TCR-T cell infusion, and through long-term follow-up for up to 1 year.

Population: Participants who received a TCR-T cell infusion (Safety Analysis Set).

Feasibility will be assessed by the number of participants who met eligibility criteria at each step of the manufacturing process, including inability to undergo apheresis, failure of product manufacture, manufactured product not infused, and successful manufacture and infusion of TCR-T cell drug product.

Time frame: From apheresis collection to the release of the final TCR-T cell drug product for infusion, estimated to be approximately 5 weeks

Population: The feasibility analysis included 14 participants who underwent apheresis with intent to manufacture TCR-T cell product. Although only 8 met criteria for lymphodepletion and were considered formally enrolled per protocol, all 14 apheresed participants were included for feasibility assessment because manufacturing could be attempted for each.

Assessed by comparing each participant's highest post-dose TCR-T cell count (copies per 1×10⁶ cells by qPCR) to the TCR-T cell count at Day 28. Percent change was calculated as: ((Day 28 - peak post-dose) / peak post-dose) × 100.

Time frame: Post-dose through Day 28

Population: 8 participants received TCR-T infusion and were included in the analysis (1 assigned at Dose Level 1, 7 assigned at Dose Level 2).

Persistence of TCR-T cells in peripheral blood was assessed by quantitative PCR for vector copy number per 1 × 10⁶ cells at baseline (1 week prior to infusion), predose (Day 0), and multiple post-infusion time points through Month 18. Only quantifiable values are summarized. Samples with Not Detected (ND) or Below the Limit of Quantitation (BLOQ) are reported as NA and excluded from summary statistics.

Time frame: Baseline through Month 18 post-infusion.

Population: Persistence analyses included the 8 participants who received TCR-T infusion (1 at Dose Level 1 and 7 at Dose Level 2). A total of 14 participants underwent apheresis, but only infused participants were evaluable for persistence. Samples with Not Detected (ND) or Below the Limit of Quantitation (BLOQ) were not quantifiable and are reported as NA. Participants without samples at a given time point were excluded.