# 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**