SITC Poster 2022 Clinical Poster.cdr
A PHASE I/II TRIAL INVESTIGATING SAFETY AND EFFICACY OF AUTOLOGOUS TAC T CELLS TARGETING HER2 IN RELAPSED OR REFRACTORY SOLID TUMORS (TACTIC-2)
INTRODUCTION
The T cell antigen coupler (TAC) is a novel, proprietary chimeric receptor that facilitates the redirection of T cells to tumor cells and activates T cells by co-opting the endogenous T cell receptor complex, aiming to elicit a safe and durable anti-tumor response. In preclinical models of cancer, TAC-engineered T cells effectively eradicate tumor cells in vitro and in vivo without toxicities typically associated with engineered T cell products.
TACTIC-2 (NCT04727151) is an open-label, multicenter phase I/II study that aims to establish safety, maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), pharmacokinetic profile, and efficacy of TAC01-HER2 in patients with HER2-positive solid tumors by immunohistochemistry that are 1+, 2+, or 3+ (i.e. breast, lung, pancreatic, colorectal, gastric, endometrial, ovarian, and others) who have progressed on prior anti-cancer therapies.
We present a clinical update from Cohorts 1-3 (9 participants) that highlights safety and efficacy data; the study further elucidates potential therapeutic impact to patients with HER2 overexpressed solid tumors.
Significant Unmet Need Beyond HER2+
Breast Cancer
TAC SCIENCE
TAC co-opts the natural TCR and provides the intracellular co-receptor function, mimicking normal TCR activation.
TRIAL DESIGN & MANUFACTURING
Phase II Dose Expansion
Fully Automated Manufacturing: 9 days; Vein-Vein Time: 21-24 Days
Group C: (1+, 2+ & 3+)
HER2 Positive
combination cohort with
immune checkpoint
inhibitor
Planned Enrollment of 35 Patients; 2nd Line + Setting
PHASE I TRIAL PROGRESS
Primary Endpoints
Safety: DLTs, MTD
- 3 consecutive days of fludarabine (Flu)
- IV (30 mg/m2) and cyclophosphamide
- (Cy) IV (300 mg/m2) with/without
- Mesna IV
Lymphodepleting Chemotherapy:
Due to national shortage of fludarabine, modified LDC given per institutional standard
Secondary Endpoints
Eligibility Criteria
Efficacy: ORR, DOR, PFS, OS, RP2D, Aes
- Patients with advanced, metastatic, unresectable solid tumors which express HER2 after at least 2 lines of therapy, at least 1 measurable lesion per RECIST version 1.1, ECOG performance score 0-1, grade 1 or baseline for any prior treatment related toxicities.
Cohorts 1 & 2 + 1st Patient in Cohort 3: Demographics and Tumor-Intrinsic Characteristics
| Median Age (Range), by Year | 64 (42-70) |
|---|---|
| Sex: Male/Female(%) | M: 6 (66.6%) |
| Sex: Male/Female(%) | F: 3 (33.3%) |
| Race(%) | White: 8 (89%) |
| Race(%) | Other: 1 (11%) |
| ECOG PS(%) | 0: 5 (56%) |
| ECOG PS(%) | 1: 4 (44%) |
| HER2 Expression(%) | 3+: 8 (89%) |
| HER2 Expression(%) | 2+/ISH+: 1 (11%) |
| Tumor Type (%) | Gastric: 3 (33%) |
|---|---|
| Tumor Type (%) | Colorectal: 3 (33%) |
| Tumor Type (%) | Gastroesophageal Junction: 2 (22%) |
| Tumor Type (%) | Gall Bladder: 1 (11%) |
| Previous Anti-Cancer Therapy Median (Range) | 4 (2-12) |
| Previous Lines of HER2 Therapy Median (Range) | 2 (1-9) |
| Previous HER2 Therapy Types (%) | Trastuzumab: 14 (51.8%) |
| Previous HER2 Therapy Types (%) | Trastuzumab Deruxtecan: 3 (11.1%) |
| Previous HER2 Therapy Types (%) | Investigative: 8 (29.6%) |
| Previous HER2 Therapy Types (%) | Pertuzumab: 1 (3.7%) |
| Previous HER2 Therapy Types (%) | Tucatinib: 1 (3.7%) |
PHASE I SAFETY DATA
Day 0 Summary of Adverse Events by Incidence
- Summary of Adverse Events by Incidence
- One CRS grade 1 event (with pyrexia as the only symptom) at DL3 resolved within 3 days.
Day 29 No Observed Immune Effector Cell-
- No Observed Immune Effector Cell- Associated Neurotoxicity (ICANS) through the first patient at DL 3
Safety Summary
- Most grade 2, 3 events were expected and related to LD chemotherapy.
CHANGES IN TUMOR MEASUREMENTS ACROSS ALL DOSE LEVELS
U Cohort 1
- Suboptimal entry DL, however 1st signal of clinical activity, showing 1 pt. with mixed response
U Cohort 2
- Original DL1
- 1 pt. with PR and 2 pts. with SD (zero change from baseline)
- 1 pt. with unconfirmed progressive disease
Follow-Up
All patients are still in 2-year follow-up per protocol, except for two patients who died due to PD in cohort 1, and another who withdrew consent in Cohort 2.
- Disease control rate of 75% at DL2, a very low dose of TAC T cell count in heavily pretreated pts. with aggressive malignancies
TUMOR ASSESSMENT: FIRST PATIENT RESPONSE
- Partial Response Observed in Patient 0203-0021
- 42 year old male with IHC 3+, HER2+ stage IVb metastatic gastric adenocarcinoma.
- Previously treated with 2 lines of HER2-directed targeted therapy + chemotherapy & palliative radiation. The patient also received bridging therapy which consisted of 3 cycles of chemotherapy.
| RECIST 1.1 Tumor Response Assessments (Measurable Disease) | ||
|---|---|---|
| Baseline | Day29 | % change |
| 20mm | 12.7mm | -36.5% |
- Stable Disease noted in both patients 0106-0016 (3+ HER2) and 0106-0006 (2+ HER2). Remarkably, no significant change in tumor size from baseline was observed in both patients.
Safety
Interim results from the Phase I TACTIC-02 study suggest that TAC-01 HER2 is safe and well tolerated, supported by the absence of DLTs and events of special interest except for one grade 1 CRS at DL3, which quickly resolved with minor intervention.
SUMMARY & CONCLUSIONS
EFFICACY
Lymph Node Reduction
Demonstrated early signals of clinical activity, highlighting a partial response in a stage IVb gastric cancer patient and a disease control rate of 75% at DL2.
- TRIAL PROGRESS: Phase I trial is ongoing and on track to be completed in Jan 2023. Enrollment completed at DL3 & patients consented to secure timely enrollment on DL4. Phase II enrollment begins in Q1 2023.
Disclosures
Dr. Benjamin L. Schlechter has no conflicts of interest to report.
Sponsorship: This Phase I/II Clinical Trial has been fully funded by Triumvira Immunologics Inc.
Contact: dadib@triumvira.com, benjamin_schlechter@dfci.harvard.edu