TAC01-HER2 elicited encouraging safety and clinical activity in patients with HER2-positive solid tumors with no dose limiting toxicities, cytokine release syndrome, or immune effector cell-associated neurotoxicity observed.
The ongoing phase 1/2 TACTIC‑2 trial (NCT04727151) revealed TAC01-HER2 to be well tolerated and show early signals of clinical activity in patients with HER2-positive solid tumors, according to Triumvira Immunologics.1
TAC01-HER2 showed encouraging safety data in both dosing cohorts with no dose limiting toxicities, cytokine release syndrome, or immune effector cell-associated neurotoxicity observed. All serious adverse events were confirmed to be unrelated to TAC01-HER2.
Additionally, early signals of clinical activity were observed in the higher of the 2 dosing cohorts with a 75% disease control rate, including 1 partial response.
“Gastric adenocarcinoma remains a deadly disease with poor outcomes. The safety profile of TAC01-HER2 has been well differentiated compared to other approved CAR T-cell therapies. Additionally, the partial response in the study in a patient with metastatic gastric cancer is promising and underscores the potential of this novel cell therapy to treat patients who need it most,” concluded Benjamin L. Schlechter, MD, Dana-Farber Cancer Institute and an investigator on the TACTIC-2 study, in the press release.
The open-label, multicenter, phase 1/2 TACTIC-2 trial aims to determine the safety, maximum tolerated dose (MTD), and recommended phase 2 dose (RP2D) of TAC01-HER2 in patients with HER2-positive solid tumors, including breast cancer, lung cancer, colorectal cancer, gastric cancer, endometrial cancer, ovarian cancer, and more which have progressed on prior anticancer therapies.2,3
Enrollment was open to patients aged 18 years and older with a recent tumor sample to confirm HER2-protein expression on tumor cell surface, relapsed or refractory disease after at least 2 prior lines of therapy, measurable disease per RECIST v1.1 criteria, a life expectancy of at least 12 weeks, adequate organ function, and an ECOG performance status of 0 or 1.
After the collection of T cells and before the administration of TAC01-HER2, patients underwent lymphodepletion, consisting of 3 consecutive days of intravenous (IV) fludarabine at 30 mg/m2 and IV cyclophosphamide at 300 mg/m2 with or without mesna IV. Four patients were treated with dose level 1 of 1.3 x 105 cells/kg, 4 patients had received dose level 2 of 6.8 x 105 cells/kg. There are also patients enrolled to receive the third dose level of 1.3 x 106 cells/kg of TAC01-HER2, and the trial is enrolling patients to receive dose level 4 of 6.8 x 106 cells/kg.
Primary end points of the trial included dose-limiting toxicities and establishing the MTD with the secondary end points of overall response rate, duration of response, overall survival, establishing the recommended phase 2 dose, and safety.
In cohorts 1 and 2 of the trial, the median age of patients was 65.5 years (range, 42-70), 62.5% of patients were male, and 87.5% were White. Half of the enrolled patients had an ECOG performance status of 0 while the other half had a status of 1. A HER2 expression of 3+ was found in 87.5% of patients while the other 12.5% had a HER2 expression of 2+/ISH+.
In regard to tumor type, 2 patients had gastric cancer, 2 patients had CRC, and 1 patient each had gastroesophageal junction cancer, gallbladder cancer, esophageal cancer, and rectosigmoid cancer.Patients had a median of 4.5 prior lines of therapy (range, 2-12), and the median number of prior lines of HER2-targeted therapy was 2 (range, 0-9). Moreover, previous HER2 therapies given to patients included trastuzumab (Herceptin; n = 5), fam-trastuzumab deruxtecan-nxki (Enhertu; n = 3), and investigative agents (n = 5).
Findings revealed that there were early signals of clinical activity observed in the second dosing cohort with a disease control rate of 75%. A patient with stage IVb metastatic gastric cancer who was heavily pre-treated and defined as 3+ HER2 by immunohistochemistry had achieved a partial response.
CT scans which were taken 29-days after dosing revealed a 36.5% reduction in tumor size in target lesions vs baseline. Further, the size of numerous metabolically active lymph nodes which were associated with the mass decreased and 2 patients in the second cohort had a significant disease burden which has been observed with stable disease with no change in tumor measurements compared to baseline.
Regarding safety, there were no dose-limiting toxicities reported in cohorts 1 and 2 and no patients experienced any grade cytokine release syndrome or immune effector cell–associated neurotoxicity.
The most common adverse effect (AE) was any grade anemia and occurred in all 8 patients. Additional any-grade AEs were decreased white blood cell count (n = 6), decreased neutrophil count (n = 6), increased alanine transaminase (n = 3), decreased platelet count (n = 2), and decreased lymphocyte count (n = 2). All serious AEs were confirmed to have been attributed to causes unrelated to TAC01-HER2 infusions.
The enrollment of the phase 1 portion of the study is expected to be completed by the end of 2022. Once the optimal dose is identified, the phase 2 registration component of the trial will be initiated in the start of 2023. The first patient in the phase 1 dose level 3 of 1-3 x 106 cells/kg has already been treated.
“These initial data encourage us as HER2 is a well-validated target with growing clinical significance. There remains a large treatable patient population beyond breast and gastric cancers with tremendous unmet need across the spectrum of HER2 expression, especially low and intermediate, and we believe TAC-T-cell therapies can be an effective way of treating these patients,” said Deyaa Adib, MD, chief medical officer of Triumvira Immunologics, in the press release.