Interim data from an ongoing investigator-sponsored clinical trial led by Baylor College of Medicine evaluating MultiTAA T cell therapy in patients with pancreatic adenocarcinoma.

Marker Therapeutics, Inc. announced interim data from an ongoing investigator-sponsored clinical trial led by Baylor College of Medicine , evaluating the Company’s MultiTAA T cell therapy in patients with pancreatic adenocarcinoma. The data were reviewed in an oral presentation during a plenary session, as well as a poster presentation, at the American Association for Cancer Research’s (AACR) Immune Cell Therapies for Cancer: Successes and Challenges of CAR T Cells and Other Forms of Adoptive Therapy conference held in San Francisco, California from July 19-22, 2019.

“Pancreatic cancer continues to be one of the most challenging solid tumor malignancies to treat and survival rates have not seen a meaningful improvement in more than 40 years,” said Brandon G. Smaglo, M.D., FACP, lead investigator and Assistant Professor of Oncology at Baylor College of Medicine. “We are encouraged by these interim data which suggest that MultiTAA therapy may contribute to more durable responses without added toxicity when used in combination with standard-of-care chemotherapy, or as a second-line therapy for patients who are chemo-refractory. Additionally, despite the particularly dense desmoplastic stroma surrounding pancreatic tumors—which has been long considered a major obstacle for T cell effectiveness—our study of patients with borderline surgically resectable disease suggests that MultiTAA cells are capable of meaningfully infiltrating the tumor.”

Interim Results : Arm A: This arm was designed to evaluate the safety and potential efficacy of using MultiTAA cells as part of first-line treatment for patients with pancreatic cancer. These patients in the chemo-responsive arm have completed or will complete at least three months of standard-of-care chemotherapy (gemcitabine/nab-paclitaxel or FOLFIRINOX) – the period during which a response to chemotherapy would typically occur – before receiving up to six administrations of MultiTAA T cells in conjunction with chemotherapy. Out of the 9 evaluable patients (one patient was too early to be evaluated): 3 patients experienced objective responses after administration of MultiTAA cells.1 patient experienced a complete response. 2 patients experienced partial responses. 4 patients experienced stable disease; 2 patients within stable disease boundaries (+20%/-30%) saw reversal of tumor growth – tumors previously growing after chemotherapy alone showed shrinkage after administration of MultiTAA cells. 1 patient experienced a mixed response (some lesions increased in size and others decreased for a net zero change in size of tumor lesions). 1 patient experienced disease progression. Overall tumor volume shrinkage was observed in six out of the eight patients with a measurable tumor after administration of MultiTAA cells. One evaluable patient did not have tumor measurements for analysis. Of the 9 evaluable patients, over half have survived to or beyond the historical median overall survival associated with their respective chemotherapy regimens, and 7 of the 9 patients remain alive. In patients responding to therapy, significant expansion of the infused MultiTAA cells was observed, along with broad-based epitope spreading, with significant expansion of endogenous T cells specific for other tumor specific antigens.

Arm B: This arm was designed to evaluate the use of MultiTAA cells as a second-line therapy for patients who have failed first-line chemotherapy. The patients in this chemo-refractory arm are either ineligible for chemotherapy or have progressed on chemotherapy and have received or are receiving up to six doses of MultiTAA T cells as a monotherapy. Of the 6 patients treated and evaluable: 3 patients experienced stable disease or clinical disease stabilization. 2 patients who previously had progressive disease experienced clinical disease stabilization for up to two months. 1 has maintained stable disease for 7 months (ongoing). 3 experienced clinical decline. Among the patients who saw clinical disease stabilization, significant expansion of the infused MultiTAA cells was observed, along with broad-based epitope spreading, with significant expansion of endogenous T cells specific for other tumor specific antigens.

Arm C : This arm was designed to assess T cell infiltration and expansion. These patients with borderline surgically resectable disease received or will receive a dose of T cells following chemotherapy, radiotherapy or combination prior to surgical resection and up to five additional doses of T cells after surgery. In these patients, MultiTAA T cells were measurable in meaningful numbers as detected by correlative analysis of resected tumor, and significant expansion of the infused MultiTAA cells was observed, along with broad-based epitope spreading, with significant expansion of endogenous T cells specific for other tumor specific antigens. Overall, investigators observed a clinical benefit correlated with the detection of tumor-reactive T cells in patient peripheral blood (Arms A, B and C) and within tumor biopsy samples (Arm C) post-infusion. T cells exhibited activity against both targeted antigens as well as non-targeted TAAs including WT-1, AFP, MART-1 and numerous antigens of the MAGE family, indicating induction of antigen/epitope spreading. No infusion-related systemic- or neurotoxicity was observed, and patients continue to be evaluated and enrolled in the trial.