About the Phase 1/2 Trial of TAC-01 in HER2-Expressing Solid Tumors

In the second of 3 videos, Paul Lammers, MD, MSc, chief executive officer of Triumvira, talks about the company’s unique T antigen coupler (TAC) T-cell technology and the ongoing phase 1/2 study evaluating the safety and efficacy of TAC-01 in HER2-expressing relapsed or refractory tumors (NCT04727151). Daniel Olson, MD, assistant professor of medicine, the University of Chicago Medicine, presented an abstract about the trial at the Society for Immunotherapy of Cancer 38th Annual Meeting held November 1-5, 2023.

Here, Lammers describes the TAC mechanisms and what sets it apart from chimeric antigen receptor (CAR) T-cell therapy.

Related: Advancements in Cell Therapy for Solid Tumors

Transcription:

0:09 | So that is an oral abstract presentation by Dr. Dan Olson, who’s an oncologist at the University of Chicago, one of our principal investigators. So basically, Dan will summarize the data coming out of our phase 1 trial, where we had 20 patients in a dose-escalation study. And we got a recommended phase 2 dose at the highest dose level, dose level 4. So let’s talk about safety first, and then we’ll move to the efficacy side of things. On the safety side, 20 patients, not a single ICU admission, right.

0:43 | We’ve only had 1 grade 3 CRS that was a case of a woman with increased liver function test, no signs or symptoms, that automatically by itself disappeared after 3 days. The levels came down. And we’ve only have 1 dose limiting toxicity which was a woman with breast cancer who had no no lung metastases, but developed pneumonitis grade 3. And she was basically given oxygen by a nasal cannula, she was given steroids, and it also resolved in 5 or 6 days. So the fact that we have not had a single ICU admission is, I mean, talk about differentiation. I mean, that is just so different. If you think about it, if you think about this Yescarta [axicabtagene ciloleucel], Kymriah [tisagenlecleucel], Carvykti [ciltacabtagene autoleucel], Abecma [idecabtagene vicleucel, patients are still required now for these marketed products to be in the clinic between 4 to 14 days. Our PIs said, guys, this is going to be an outpatient procedure. Patient comes in, gets a cell bag, and stays for observation the rest of the day, then goes home.

1:45 | Most cases of CRS that we saw grade 1 and 2 were pyrexia, was fever, which is normal, not to be unexpected if you get a bunch of cells infused, and you give Tylenol and they’re okay. So the safety has truly been remarkable. And now now let’s go to the efficacy side of things. So we’re focusing on HER2, right, which is a well-known target of expression in solid tumors. So typical phase 1, you get a mixed bag of patients, you have breast, you have lung, you have gastric, gastroesophageal, ovarian cancer, you name it. Patients have been heavily, heavily pretreated. Especially the poor breast cancer patients. Some of them had 10 to 12 previous therapies. You know, look, these poor women have been beaten up, you know, as you can imagine, and they’re willing and, thank you, for them big time. They’re willing to participate. It’s a last resort thing.

2:32 | We treated 20 patients. So dose levels 2, 3, and 4 are really the ones that we want to look at. And we have 16 patients there. And we had 11 out of 16 had a response, either a stable disease, and we had 2 very strong partial responses, and I’ll mention those in a minute. So overall, it was a really good disease control rate, about 69%. And specifically, there were 7 patients with gastric or gastroesophageal cancers where we saw stable disease, and those 2 PRs, so 2 out of 7, so that’s a 29% objective response rate. Now people say, well, Paul, but it’s not that high. Well, the only approved product for third-line gastric is Lonsurf [trifluridine/tipiracil] that has a 4% ORR, as in 4%. So we feel that is a low-hanging fruit for us. So therefore, phase 2 now. We’re going to have patients earlier on in the treatment journey, i.e. no more than 4 previous therapies. Only gastric and gastroesophageal. We will re-dose, because the key thing is in cell therapy, especially in solid tumors, you need to have the ability to provide maximum clinical benefit to a patient so re-dosing is absolutely critical. So for most patients, when we manufacture the TAC T cells, we get 2 bags out of a single run in the cocoon. One goes to the patient, the other 1 goes into fridge. If the patient at day 29, when we do the scan, has either stable disease or a PR, we give a second dose to maximize the benefit for the patient, right.