# INTRODUCTION

- The T cell antigen coupler (TAC) is a novel, proprietary chimeric receptor that facilitates the re-direction of T cells to tumor cells and activates T cells by co-opting the endogenous T cell receptor complex, with the goal 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 TAC-related toxicities.

- 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 (i.e. breast, lung, pancreatic, colorectal, gastric, endometrial, ovarian, and others) whom have progressed on prior anti-cancer therapies.

- We present a clinical update from Cohorts 1 & 2 (8 participants) that highlights safety and efficacy data; the study further elucidates potential therapeutic impact to patients with HER2 overexpressed solid tumors.

## TAC01-HER2 SCIENCE

## Key features of TAC01-HER2 technology:

- TAC01-HER2 functions independently of MHC
- TAC01-HER2 requires endogenous TCR for T cell activation
- TAC01-HER2 incorporates the co-receptor and recruits the TCR complex, mimicking natural TCR activation

The TAC receptor interacts directly with the TCR-CD3 epsilon domain.

The TAC receptor also binds directly to the tumor antigen. Initiating the first step in T cell activation, which then leads to full T cell activation.

The TAC receptor then signals through the CD3-TCR complex.

## TRIAL DESIGN & MANUFACTURING

This ultimately results in tumor cell lysis.

**(1+, 2+ & 3+) HER2 Positive Breast Cancer**
**Planned Enrollment of 23 Patients; 2nd Line + Seeing**  
**(1+, 2+ & 3+) HER2 Positive non-Breast Cancer**
**Planned Enrollment of 35 Patients; 2nd Line + Seeing**

**Lymphodepleting Chemotherapy: 3 consecutive days of fludarabine (Flu) IV (30 mg/m2) and cyclophosphamide (Cy) IV (300 mg/m2) with/without Mesna IV**

## PHASE I TRIAL ENROLLMENT

## Primary Endpoints

## Safety: DLTs, MTD

## Secondary Endpoints

## Efficacy: ORR, DOR, PFS, OS, RP2D, AEs

## Eligibility Criteria

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: Demographic & Tumor-Intrinsic Characteristics**

| Median Age (Range), by Year | | 65.5 (42-70) | Tumor Type (%)GastricColorectalGastroesophageal JunctionGall BladderEsophagealRectosigmoid |
| --- | --- | --- | --- | --- | --- |
| Sex: Male/Female (%) | M | 5(62.5%) | Tumor Type (%)GastricColorectalGastroesophageal JunctionGall BladderEsophagealRectosigmoid | | |
| Sex: Male/Female (%) | F | 3(37.5%) | Tumor Type (%)GastricColorectalGastroesophageal JunctionGall BladderEsophagealRectosigmoid | | |
| Race (%) | White | 7(87.5%) | Tumor Type (%)GastricColorectalGastroesophageal JunctionGall BladderEsophagealRectosigmoid | Previous Anti-Cancer Therapy Median (Range) | 4.5(2-12) |
| Race (%) | Other | 1(12.5%) | | Previous Anti-Cancer Therapy Median (Range) | 4.5(2-12) |
| ECOG PS (%) | 0 | 4(50.0%) | Previous Lines of HER2 Therapy Median (Range) | 2(0-9) | |
| ECOG PS (%) | 1 | 4(50.0%) | Previous Lines of HER2 Therapy Median (Range) | 2(0-9) | |
| HER2 Expression (%) | 3+ | 7(87.5%) | Previous HER2 Therapy Types (%)TrastuzumabTrastuzumab DeruxtecanInvestigative | 5(62.5%) | |
| HER2 Expression (%) | 2+/ISH+ | 1(12.5%) | Previous HER2 Therapy Types (%)TrastuzumabTrastuzumab DeruxtecanInvestigative | 3(37.5%)5(62.5%) | |

## PHASE I SAFETY DATA

## Baseline Domain
## Day 0 Summary of Adverse Events by Incidence

**Summary of Adverse Events by Incidence**

## Safety Summary

**Frequency**

**No Observed Cytokine Release Syndrome (CRS) in Cohorts 1 & 2**

**No Observed Immune Eector Cell-Associated Neurotoxicity (ICANS) in Cohorts 1 & 2**

## BIOMARKER DATA: FIRST PATIENT RESPONSE

**All Serious Adverse Events are Confirmed to be Unrelated to TAC-01 HER2 Infusions**

**Blood Pharmacokinetics**

**Blood PK Data from Patient 0203-0021**

Low but definitive presence TAC01-HER2 cells indicated by elevated TAC copies at day 15 marker. Compared against average (+/- SEM) of other cohort 1 & 2 patients (n=6).

**Pt. 0203-0021**  
Avg (+/-SEM) of other cohort 1&2 pts. (n=6)

**Cytokine Data from Patient 0203-0021**
Serum cytokine analysis indicates slightly elevated levels in patient 0203-0021 vs others. Absence of IL-6 confirms lack of CRS. This is subtle, but intriguing biomarker data that corroborates safe response in patient 0203-0021.

## EFFICACY: DOSE LEVEL 2 RESPONSE

**Dose Level 2 (6-8 x 10^5 cells/kg)**
**Day 28 Change in Lesion Sizes from Baseline**

**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 + chemotherapy & palliative radiation.

| RECIST 1.1 Tumor Response Assessments (Measurable Disease) | | |
| --- | --- | --- |
| Baseline | Day29 | % change |
| 20mm | 12.7mm | -36.5% |

## TUMOR REGRESSION: FIRST PATIENT RESPONSE

**Gastrohepatic Lymph Node in Patient 0203-0021**

**Baseline**
**Day 0**
**(2.00 cm)**

**Gastrohepatic Node Reduction Perioportal Mass Reduction**

| PET Scan Results(Evaluable disease) | | | | |
| --- | --- | --- | --- | --- |
| Tumor | Size Pre | Size Post | SUVmax pre TAC-T | SUVmax post TAC-T |
| Right lower paraoesophageal node at the level of T10 | - | - | 6.5 | 3.2 |
| Gastrohepatic ligament lymph nodes | 2.4x2.3cm | 1.9x1.2cm | 20.5 | 15 |
| Portacaval nodal mass* | 5.1x4.0cm | 4.8x3.4cm | 22.1 | 29 |
| Left common iliac lymph node | No gross interval change per radiologist | | 19.3 | 23.1 |

## Lymph Node Reduction

**There has been overall interval decreased size of previously noted metabolically active lymph nodes associated with the mass, however with persistent intense metabolic activity in most of them.**

*Despite SUVmax increase the lesions shows more extensive photopenic areas, representing cystic/necrotic change cancer cell death. ** There was also a stable cystic/necrotic node cancer cell death.

## SUMMARY & CONCLUSIONS

## SAFETY

## EFFICACY

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 such as CRS & ICANS.

Demonstrated early signals of clinical activity, highlighting a **partial response in a stage IVb gastric cancer patient** and a disease control rate of 75% in cohort 2.

## TRIAL PROGRESS

**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

This study is ongoing with further investigation of TAC-01 HER2 in the remaining phase I trial, with enrollment in dose level 3 & patients consented for dose level 4. Phase II enrollment begins in 2023.