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European Society for Medical Oncology Congress (ESMO)

“The worry when we started was that we wouldn't see benefit, but we've seen it. So this really does 2 things. Number 1, it's an avenue for treatment for a significant subset of patients with advanced malignancy... But significantly, if this strategy is successful, this may open the world of T-cell therapies to the solid tumor world, in a way that we really have not had access to [in a large scale with] CAR-T or tumor-infiltrating lymphocyte therapies, due to the limitations of those modalities.”

Triumvira Immunologics’ TAC01-HER2, an investigational HER2-targeted T-cell antigen coupler (TAC) T-cell therapy, is currently being evaluated in the phase 1/2 

(NCT04727151) for the treatment of patients with HER-2 positive solid tumors.

Benjamin L. Schlechter, MD, instructor, medicine, Harvard Medical School, and Dana-Farber Cancer Institute, an investigator for the trial, recently presented data from TACTIC-2 at the 

European Society for Medical Oncology (ESMO) Congress 2022

, taking place September 9-13, in Paris, France, and virtually.

, Schlechter discussed the key findings that have come out of the clinical trial so far, highlighting a patient’s objective response at 29 days as particularly impressive. He also went over what he sees as the potential advantages of TAC01-HER2 compared to the current standard of care for patients with HER2-positive solid tumors. Schlechter additionally discussed some challenges of the current trial and potential areas for further study. He concluded by recommending a re-examination of immunotherapy naming conventions in order to make the terminology more descriptive and educational for both the broader clinical community and patients.

Schlechter discussed the potential advantages of TAC01-HER2 over current standards of care.

Benjamin L. Schlechter, MD, on TAC01-HER2 in HER2-Positive Solid Tumors 

“There's sort of 2 big groups of HER2 solid tumors: there's the breast cancer population, and there's everybody else. The reality in breast cancers is there's a myriad of effective treatments: cytotoxics, antibody drug conjugates, combinations, monoclonal antibodies, and targeted therapies. And those have had much less benefit in other HER2-positive malignancies... HER2 therapy has not been as effective in GI malignancies and other malignancies as it has been in breast cancer.”

While commercially available treatment options have shown efficacy in treating HER2-positive solid tumors in patients with breast cancer, these same treatments have been less effective in treating patients with HER2-positive solid tumors in other types of cancers, such as gastrointestinal (GI) malignancies.

Benjamin L. Schlechter, MD, instructor, medicine, Harvard Medical School, and Dana-Farber Cancer Institute, recently presented data from the ongoing phase 1/2 TACTIC-2 clinical trial (NCT04727151) of TAC01-HER2, an investigational HER2-targeted T-cell antigen coupler (TAC) T-cell therapy intended to address unmet needs for patients with HER2-positive solid tumors, at the 

, Schlechter discussed the current state of care for patients with HER2-positive solid tumors, explaining the differences that exist in available options between the population of patients with HER2-positive breast cancers and patient populations with other types of HER2-positive solid tumors. He then gave an overview of the design of the TACTIC-2 clinical trial, describing the mechanism of the cell therapy and its intended method of avoiding off-target toxicity. He also briefly discussed the early safety and efficacy data that has come out of the clinical trial so far.

Schlechter discussed the design of the TACTIC-2 clinical trial for patients with HER2-positive solid tumors. 

Benjamin L. Schlechter, MD, on Addressing Unmet Needs in HER2 Positive Solid Tumors 

“We are planning to be able to treat over 2000 patients next year. So by commissioning additional Cocoons from Lonza, with this state-of-the-art technology, our yield has been 100%.”

The HER2-targeted T-cell antigen coupler (TAC) T-cell therapy TAC01-HER2 (Triumvira Immunologics) demonstrated early signs of clinical activity and a manageable safety profile, according to updated data from the phase 1/2 TACTIC-2 study (NCT04727151). A patient with stage 4b gastric cancer treated with TAC01-HER2 had a partial response and those in cohort 2 experienced a disease control rate of 75%.

The trial will be enrolling in its phase 2 portion in the beginning of 2023. These data were presented at the 

, taking place September 9-13, in Paris, France, and virtually, by Benjamin L. Schlechter, MD, instructor, medicine, Harvard Medical School, and Dana-Farber Cancer Institute.

spoke with the senior author of the poster, Deyaa Adib, MD, who is chief medical officer of Triumvira Immunologics, to learn more about Triumvira’s programs and technologies. He discussed an upcoming investigational new drug application (IND) submission in 2023 for claudin 18.2-positive cancers including gastric, pancreatic, ovarian, and lung cancers. He also discussed Lonza’s Cocoon technology that Triumvira is using in its programs and its advantages in the space.

Click here to read more coverage of ESMO Congress 2022.

Schlechter BL, Ileana Dumbrava EE, Olson D, et al. A phase I/II trial investigating safety and efficacy of autologous TAC T-cells targeting HER2 in relapsed or refractory solid tumors. Presented at: ESMO Congress 2022, September 9-13, Paris, France. Poster #778TiP

The chief medical officer of Triumvira Immunologics discussed the company’s future plans. 

Deyaa Adib, MD, on Optimizing Manufacturing of Solid Tumor Cell Therapies 

"The most valuable advantage we see so far would be the safety profile associated with HER2-TAC T-cells and it is very well differentiated thus far compared to approved CARs. So far we have not seen any dose limiting toxicities, cytokine release syndrome, or neurotoxicity in dose levels 1 and 2."

Triumvira Immunologics’ TAC01-HER2, a HER2-targeted T-cell antigen coupler (TAC) T-cell therapy, was well-tolerated with early signs of clinical activity. In new data from cohort 2 of the phase 1/2 TACTIC-2 study, the therapy yielded a partial response in a patient with stage 4b gastric cancer and a 75% disease control rate.

Data from the study were presented by Benjamin L. Schlechter, MD, instructor, medicine, Harvard Medical School, and Dana-Farber Cancer Institute, at the 

, held September 9-13, in Paris, France. The trial will be enrolling in its phase 2 portion in the beginning of 2023.

 spoke with senior author Deyaa Adib, MD, chief medical officer, Triumvira Immunologics, to learn more about unmet needs in patients with solid tumors. He discussed the advantages of the TAC T-cell technology in addressing these unmet needs, including a positive safety profile with lower rates of cytokine release syndrome compared to those seen in other cell therapy trials.

The chief medical officer of Triumvira Immunologics discussed how TAC01-HER2 could address unmet needs in treating solid tumors. 

Deyaa Adib, MD, on Safety Advantages of TAC T-Cell Therapy in Solid Tumors 

“There used to be a paucity of industry interested in NK cell biology and now that's exploded. Now, everybody's interested in autologous NK cells or induced pluripotent stem cells-derived NK cells.”

Natural killer (NK) cell approaches are being investigated more and more for treating both hematologic malignancies and solid tumors. Presentations on new NK cell approaches were given at the 

European Society of Medical Oncology (ESMO) Congress 2022

, held September 9-13, in Paris, France. One such presentation was given by Jeffrey Miller, MD, professor and deputy director of the Masonic Cancer Center of the University of Minnesota, on GTB-5550, a B7H3 tri-specific killer engager (TriKE) that specifically stimulated expansion of natural killer (NK) cells in preclinical models of multiple cancers.

The novel dual camelid (cam) TriKE contains wild type interleukin-15 and 2 cam engagers that target CD16 on NK cells and B7H3 on multiple solid tumors. The data presented demonstrated GTB-5550'sability to increase activity of NK cells against cancer cells after stimulation.

 spoke with Miller to learn more about NK cell research and other promising approaches discussed at the ESMO Congress. He touched on new avenues of research including NK cell combinations with PD1 blockades and different platforms to produce NK cells.

Miler JS, Zorko N, Merino A, et al. B7H3-targeted tri-specific killer engagers deliver IL-15 to NK cells but not T-cells, and specifically target solid tumors as a pan-tumor antigen strategy mediated through NK cells. Presented at: ESMO Congress 2022, September 9-13, Paris, France.

The deputy director of the Masonic Cancer Center discussed trends of presentations from ESMO 2022. 

Jeffrey Miller, MD, on Emerging Research With Natural Killer Cells 

“As of August, we have completed dose levels 1 and 2, in the escalation component of our phase 1 trial. We’ve seen a very pleasant surprise, a partial response in a patient who has stage 4b gastric cancer at the second dose level, which is still a very low dose level. This patient has metastatic disease, and essentially had passed 2 prior treatment lines, including HER2-targeted therapies.”

TAC01-HER2 (Triumvira Immunologics), a HER2-targeted T-cell antigen coupler (TAC) T-cell therapy, was well-tolerated and demonstrated early signs of clinical activity, including a partial response in a patient with stage 4b gastric cancer and a 75% disease control rate in cohort 2.

These data, from the phase 1/2 TACTIC-2 study, were presented at the 

, held September 9-13, in Paris, France, by Benjamin L. Schlechter, MD, instructor, medicine, Harvard Medical School, and Dana-Farber Cancer Institute.

spoke with Deyaa Adib, MD, chief medical officer, Triumvira Immunologics, and senior author of the poster to learn more about the study and its recent updates. He discussed the trial’s progress so far and the cases of stable disease and partial response. The trial will be enrolling in its phase 2 portion in the beginning of 2023.

The chief medical officer of Triumvira Immunologics discussed updates from the TACTIC-2 study presented at ESMO Congress 2022. 

Deyaa Adib, MD, on Evaluating HER2 TAC T-Cell Therapy in Solid Tumors 

“We learned [in a previous study] that the immune engager to the NK cell is critically important. And while that study was ongoing, we discovered that if we took a nanobody, single domain antibody to engage CD16, we had significantly greater potency. So that's really the premise for putting this together.”

GTB-5550, a B7H3 tri-specific killer engager (TriKE) specifically stimulated expansion of natural killer (NK) cells in preclinical models of multiple cancers. These data were presented at the 

, held September 9-13, in Paris, France, by Jeffrey Miller, MD, professor and deputy director of the Masonic Cancer Center of the University of Minnesota.

GTB-5550 is a novel dual camelid (cam) TriKE that contains wild type interleukin-15 as well as 2 cam engagers to target CD16 on NK cells and B7H3 on multiple solid tumors. Miller and colleagues demonstrated increased activity of NK cells against cancer cells after stimulation with the TriKE engager.

spoke with Miller to learn more about the study’s results and the importance of improving targeting and engagement of NK cells with antibodies. He also discussed the potential for a clinical trial in the near future investigating the approach.

The deputy director of the Masonic Cancer Center discussed the preclinical findings of his study on a TriKE engager and NK cells. 

Jeffrey Miller, MD, on Engaging NK Cells in Solid Tumors 

“I’m excited about cellular therapy in general in solid tumors... I am really optimistic because I do think that, like in hematologic malignancies, such as lymphoma, it's just a matter of time before we kind of tweaked the technology to have higher efficacy and longer efficacy in these patients who after standard chemo really have no other options.”

Patients with metastatic ovarian, urothelial, gastroesophageal, and head and neck cancers remain without many options when early lines of treatment are not successful. T-cell receptor (TCR) engineered T-cell therapy is being explored as a potential option to address this unmet medical need.

David S. Hong, MD, professor and deputy chair, department of investigational cancer therapeutics, MD Anderson Cancer Center, The University of Texas, recently 

presented data from the phase 1 SURPASS clinical trial

 (NCT04044859), which is investigating ADP-A2M4CD8, a CD8+ TCR T-cell therapy, at the 

2022 European Society for Medical Oncology (ESMO) Congress, September 9-13, in Paris, France

, Hong explained how ADP-A2M4CD8 functions and gave an overview of the study’s findings so far. He also discussed the limitations of the trial and potential avenues for future research. In particular, he mentioned future plans to investigate the therapy in combination with checkpoint inhibitors, and additionally pointed out the need to further investigate means of identifying which patients can benefit from TCR T-cell therapy. He also expressed optimism about the future of cell therapy for the treatment of solid tumors in general.

Hong presented data from the SURPASS clinical trial at the 2022 European Society for Medical Oncology (ESMO) Congress.

David S. Hong, MD, on the SURPASS Clinical Trial and TCR T-cell Therapy in Solid Tumors 

“Our principle using the bridging drug is only to stabilize. We do not hope to choose a very effective method to make our patient better... in fact, we cannot do that because in the cell therapy stage we definitely have no very good choice.”

European Society for Medical Oncology (ESMO) 2022 Congress

, September 9-13, 2022, in Paris, France, Weijia Fang, MD, Department of Medical Oncology, The First Affiliated Hospital of Zhejiang University, presented data from a phase 1 clinical trial (NCT05028933) for 

, an investigational chimeric antigen receptor (CAR) T-cell therapy which targets the EpCAM protein. The ongoing clinical trial is treating patients with advanced gastric and colorectal cancers who have no standard treatment options remaining.

, Fang commented on a limitation of the clinical trial’s design that was pointed out by Alessandra Curioni, MD, Center of Hematology and Oncology, University Hospital Zurich, during an invited discussion of the study presentation at ESMO. The limitation related to the use of a bridging chemotherapy before the administration of IMC001.

Guoqiang Ai, MD, Immunofoco Biotech Co., also joined the interview to expand on future plans for the clinical trial, describing the planned second stage, which will combine IMC001 with radiofrequency or microwave ablation therapy. Fang rounded out the interview by discussing potential future research into methods of determining which patients can benefit most from cell therapies, mentioning liquid biopsy as an area of interest.

Fang commented on a limitation of the clinical trial pointed out at the European Society for Medical Oncology (ESMO) 2022 Congress. 

Weijia Fang, MD, and Guoqiang Ai, MD, on the Future of IMC001 in Gastric and Colorectal Cancer

“The emphasis I will place is, first, we have 8 patients now, 4 with gastric cancer and 4 with colorectal cancer. The second point is that we have no dose limiting toxicities observed.”

Gastrointestinal cancers remain a leading cause of cancer-related deaths in China, and for patients with advanced colorectal and gastric cancers, treatment options are limited.

, Weijia Fang, MD, Department of Medical Oncology, The First Affiliated Hospital of Zhejiang University, and Tianhang Luo, MD, Gastrointestinal Surgery Department, Shanghai Changhai Hospital, discussed unmet needs for patients with advanced colorectal and gastric cancers and IMC001, an investigational chimeric antigen receptor (CAR) T-cell therapy which targets the EpCAM protein. Fang recently discussed the ongoing phase 1 clinical trial (NCT05028933) for IMC001 in a 

presentation at the European Society for Medical Oncology (ESMO) 2022 Congress

, September 9-13, 2022, in Paris, France.

Fang explained the key findings that have come out of the clinical trial so far, discussing the safety profile and pointing out that no dose-limiting toxicities have been observed so far. Luo discussed potential advantages of IMC001 compared with current standards of care, noting that cytoreductive surgery has been an ineffective treatment for patients with advanced gastric cancers with metastasis.

Fang recently presented at the European Society for Medical Oncology (ESMO) 2022 Congress.

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