654 A phase I/II trial investigating safety and efficacy of autologous TAC01-HER2 in relapsed or refractory solid tumors
Bibliographic record
Abstract
<h3>Background</h3> Despite therapeutic developments for patients with advanced HER2+ solid tumors, significant unmet medical needs still exist. The T cell antigen coupler (TAC) technology is an approach to modifying T cells <i>ex vivo</i>, which allows recognition and cytotoxicity of tumor cells by co-opting the natural T cell receptor. TAC T cells demonstrate a safer profile than chimeric antigen receptor T cells. TAC01-HER2 is an autologous T-cell product comprising T cells expressing HER2 TAC. <h3>Methods</h3> The ongoing clinical trial (NCT04727151) is evaluating the safety and preliminary anti-tumor activity of TAC01-HER2 treatment of HER2+ solid tumors. Subjects undergo leukapheresis followed by low-intensity lymphodepletion chemotherapy prior to TAC01-HER2 infusion. In phase I dose escalation, TAC01-HER2 is administered at increasing doses (Cohorts 1–4) in adult subjects after ≥2 lines of therapy. Dose limiting toxicities (DLT) are assessed up to 28 days from TAC01-HER2 infusion. In Phase II, dose expansion groups will further evaluate the efficacy, safety, and pharmacokinetics of the optimal TAC01-HER2 dose in gastric/GEJ tumors. <h3>Results</h3> As of 5 June 2023, 20 patients with solid tumors have been treated in Cohorts 1–4. Three were HER2 1+ or 2+/FISH-. One DLT event of grade (G) 3 pneumonitis has been reported in 1 subject in Cohort 4. No neurotoxicity has been reported. Most subjects treated at Cohorts 3–4 experienced cytokine release syndrome (CRS) which resolved with supportive therapy. Thirteen subjects have reported a total of 26 serious adverse events, with 1 G3 pneumonitis, 4 CRS (1 G1, 3 G2 and 1 G3) and 1 G3 bronchial hyperreactivity related to TAC01-HER2. A 67% disease control rate (DCR) was observed in Cohorts 2–4 at first restaging after TAC01-HER2 infusion. For gastric/GEJ subjects of the same Cohorts, DCR was 83%. 3 months after TAC01-HER2 infusion, DCR was 33.3% for all subjects of Cohorts 2–4 and 50% for gastric/GEJ subjects. Two patients had a partial response (PR). At Cohort 4, a PR was observed in a subject with GEJ (HER2 2+, FISH+) with 100% reduction of target lesion. This patient had progressed on 4 prior lines of therapy including trastzumab and trastuzumab deruxtecan. <h3>Conclusions</h3> Treatment with TAC01-HER2 showed manageable safety and promising clinical activity in a heavily pre-treated cancer population. The recommended phase 2 dose was identified as dose level 4 (6–8 x 10<sup>6</sup> cells/kg). <h3>Trial Registration </h3> www.clinicaltrials.gov, NCT04727151 <h3>Ethics Approval</h3> This study obtained ethics approval from the following IRBs: UHN, #21-5026 Rutgers, #Pro2021002270 MD Anderson Cancer Center, #2020-1161_MOD007 University of Chicago, #IRB20-1944-AM005 Dana Farber Cancer Institute, #21-062 All participants gave informed consent before participating in this study.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".