Instructor, Medicine, Harvard Medical School and an attending Physician, Medical Oncology, Dana-Farber Cancer Institute.

Dr Schlechter on Updated Data for Botensilimab Plus Balstilimab in MSS mCRC

“The benefit of the [combination] is maintained and the toxicity is similar across all lines of therapy, which is a novel finding, and a very important finding [with] this combination of botensilimab and balstilimab.”

Benjamin L. Schlechter, MD, of Dana-Farber Cancer Institute, discussed updated data from an expanded cohort of patients with previously treated, microsatellite-stable (MSS) metastatic colorectal cancer (mCRC) and no active liver metastases treated with the Fc-engineered, CTLA-4 inhibitor botensilimab in combination with the anti–PD-1 antibody balstilimab during the phase 2 C-800-01 trial (NCT03860272).

2025 ESMO Gastrointestinal Cancers Congress

, findings from the updated analysis included 123 patients with pretreated MSS mCRC, expanding on previously published data from 77 patients. At a median follow-up of 18.0 months (range, 0.7-53.3), the overall response rate (ORR) was 20% (95% CI, 13%-28%), with a disease control rate (DCR) of 69% (95% CI, 60%-77%) at 6 weeks. Median progression-free survival (PFS) was 4.0 months (95% CI, 2.8-4.1), and the median overall survival (OS) reached 20.9 months (95% CI, 16.2-26.6). Durable benefit was further supported by a median duration of response (DOR) of 16.6 months (95% CI, 5.7-not reached). Additionally, the clinical benefit rate was 28% (95% CI, 20%-36%) at week 24.

Schlechter emphasized the consistency of clinical activity across treatment-refractory subsets, including a 37-patient fourth- or later-line subgroup lacking available standard therapies; the ORR in this group was 19% (95% CI, 8%-35%) with a median OS of 22.5 months (95% CI, 12.6-NR). Notably, efficacy outcomes were similar regardless of prior lines of therapy, underscoring the immune-driven mechanism of action of the regimen.

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Benjamin L. Schlechter, MD, discusses efficayc and safety of botensilimab in combination with the anti–PD-1 antibody balstilimab in mCRC.

Benjamin L. Schlechter, MD, senior physician, Dana-Farber Cancer Institute, instructor, medicine, Harvard Medical School, discusses the future implications of TAC01-HER2 therapy in patients with HER2-positive solid tumors.

The ongoing, phase 1/2 TACTIC-2 trial (NCT04727151) is evaluating the efficacy and safety of autologous TAC01-HER2 T-cell therapy in patients with HER2-positive breast, colorectal, gall bladder, gastroesophageal junction (GEJ), gastric, esophageal, lung, and ovarian cancers.

Interim findings from this trial, which were presented at the 2023 ASCO Annual Meeting, showed 2 partial responses with the therapy, 1 in a patient with refractory GEJ cancer, and 1 in a patient with refractory gastric cancer. In the patients with gastric, GEJ, or esophageal cancer, the disease control rate (DCR) was 83% and the overall response rate was 33%. In heavily pretreated patients, the DCR was 67%. One dose-limiting toxicity (DLT), grade 3 pneumonitis, was observed, and 1 patient had grade 3 cytokine release syndrome. No incidence of immune effector cell–associated neurotoxicity syndrome has been reported.

These findings indicate that HER2 can be targeted safely and effectively in several solid tumor populations, Schlechter says. The differences in responses between the heavily pretreated breast cancer population and the gastrointestinal (GI) cancers population may have arisen because of the biology of each disease, Schlechter explains. The patients with breast cancer were pretreated with chemotherapy and HER2-directed therapies, which bind differently to TAC01-HER2 and create a tumor microenvironment that may suppress immune responses to this therapy, Schlechter notes. However, the patients with GI cancer were less heavily pretreated and therefore may have had a more favorable tumor microenvironment for TAC01-HER2, according to Schlechter. In addition, heavily pretreated patients have inferior T cells, which may produce inferior outcomes when generated as effector T-cell therapies, Schlechter says. Delivering TAC01-HER2 as an earlier line of therapy may produce optimal patient outcomes, Schlechter notes.

Moreover, these findings demonstrate that TAC01-HER2, a non-CAR T-cell therapy, can safely target HER2, which is expressed on both tumor and normal tissue, Schlechter emphasizes. Although other HER2-directed therapies can produce excessive toxicities, TAC01-HER2 does not cause as many off-target effects and lowers the risk for DLTs, Schlechter says. A T-cell therapy that is slightly less effective than conventional treatment options but produces fewer DLTs is a favorable alternative compared with a drug that may become unusable in many patients because of its toxicity profile, Schlechter concludes.

Benjamin L. Schlechter, MD, discusses the future implications of TAC01-HER2 therapy in patients with HER2-positive solid tumors.

Benjamin L. Schlechter, MD

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Dr Schlechter on Updated Data for Botensilimab Plus Balstilimab in MSS mCRC

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