Dr Haldar on the Future Directions for Evaluating NeoAg-VAX in Colorectal Cancer

“Since we didn't see a lot of clinical efficacy in this population of patients who were heavily pretreated with prior lines of chemotherapy and had a high disease burden of metastatic tumors, we're planning to now study this vaccine in an MRD clinical setting.”

S. Daniel Haldar, MD, assistant professor in the Department of Gastrointestinal Medical Oncology in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, highlights the future directions for evaluating NeoAg-VAX, the personalized neoantigen vaccine, with or without pembrolizumab (Keytruda), for the treatment of patients with colorectal cancer.

In an investigator-initiated, single-center, open-label, nonrandomized phase 1 study (NCT02600949), patients with microsatellite stable metastatic colorectal cancer (mCRC) were treated with NeoAg-VAX alone (cohort A, n = 13) or NeoAg-VAX plus a PD-1 inhibitor (cohort B, n = 15). Notably, NeoAg-VAX was manufactured within 12 weeks of enrollment with at least 1 dose given, which indicated a feasibility rate of 85.7% in 24 of 28 patients. Additionally, the objective response rate (ORR) was 7.1%, in which 2 patients achieved a partial response per RECIST 1.1 criteria. The median progression-free survival (PFS) was 2.9 months, and the 12-week PFS rate was 57.1%.

Data from the study revealed that NeoAg-VAX did not significantly improve the clinical efficacy in heavily pretreated patients with microsatellite stable mCRC who received prior lines of chemotherapy, Haldar began. Nevertheless, he noted that there are plans to evaluate NeoAg-VAX in the minimal residual disease setting, specifically in patients who may have evidence of circulating tumor DNA positivity following surgical resection of their tumors. He emphasized that this patient population may benefit from the efficacy of the cancer vaccine, which could include patients with CRC and pancreatic cancer.

The study included patients with biopsiable disease who had received 1 or more lines of standard therapy, and an ECOG performance status of 0 or 1. Of note, patients in cohort A were treated with NeoAg-VAX alone and those in cohort B were treated with NeoAg-VAX plus 200 mg of intravenous pembrolizumab every 3 weeks. The vaccine was administered subcutaneously with topical imiquimod adjuvant on weeks 0, 1, 3 to 6, 9, 12, 15, 18, 21, 27, 30, 39, and 51. The primary end points included feasibility and toxicity; secondary end points included ORR, PFS, 12-week PFS, and T-cell response by IFNγ ELISPOT.