GEN-001/Avelumab Combination Induces Antitumor Activity in Gastric and GEJ Cancer

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Treatment with avelumab (Bavencio) plus GEN-001 in patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma has demonstrated positive antitumor activity, according to an announcement by Genome & Company.¹

The finding comes from a phase 2 study (NCT05419362) of GEN-001 in combination with avelumab, for which the primary end point is objective response rate (ORR), and the secondary end points are the incidence of adverse events (AEs), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). An exploratory end point in the study is analyzing microbiota.

The ORR shown during the interim analysis met the pre-determined criteria, and there were no safety concerns with the combination. Based on the positive results, the independent data monitoring committee (IDMC) has recommended that the study advance to stage 2 without modifications. The IDMC also recommended enrolling an additional 21 patients with advanced gastric/GEJ adenocarcinoma.

Full details from the interim analysis will be presented at a medical meeting during the second half of 2023. The developer of GEN-001, Genome & Company, also expects to report top-line data from the study during the second half of 2024.

"There is a strong unmet medical need to establish third line of therapy for GC/GEJ patients compared with the establishing 1st and 2nd lines of therapy. Hence, the pre-planned interim result of this trial is quite interesting. We continue to enroll patients and look forward to seeing the final analysis of this trial soon,” said Jeeyun Lee, MD, professor, department of Hematology and Oncology, Samsung Medical Center, in a press release.

The phase 2 study aims to enroll 50 patients with gastric/GEJ adenocarcinoma. Patients in the study are administered 3x1011 colony-forming units of GEN-001 in once-daily capsules along with avelumab 800 mg via intravenous infusion, once every 2 weeks.²

To be eligible for inclusion in the study, patients must be 19 years of age or older. All patients are required to have histological or cytologically confirmed unresectable, recurrent, locally advanced, or metastatic gastric/GEJ adenocarcinoma, an ECOG performance status of 0 or 1, and adequate organ function. In addition, patients must have documented radiographic disease progression after 2 or more prior lines of therapy, be PD-L1 positive, have measurable disease per RECIST v1.1, and an estimated life expectancy of at least 3 months.

Patients are excluded from the study due to certain active treatments, previous therapies, and having comorbidities that may interfere with GEN-001/avelumab.

"We attach great significance to presenting data-driven results for the first time through Phase II clinical trials on gastric cancer patients using the immuno-oncology microbiome therapeutic, GEN-001, in combination with avelumab from Merck KGaA, Darmstadt, Germany and Pfizer Inc,” said Pae Jisoo, chief executive officer, Genome & Company, in the press release. “We intend to obtain phase II clinical data for 'GEN-001' within next year and to discuss a licensing agreement with partners or global big pharmaceutical companies."

_REFERENCES:

_{1. Positive results from interim analysis of 'GEN-001' plus avelumab (Bavencio®) phase II trial. News release. Genome & Company. May 19, 2023. Accessed May 19, 2023. https://prn.to/45t0F39}

_{2. GEN-001 in combination with avelumab for patients with PD-L1 positive gastric cancer. Clinicaltrials.gov. Updated June 16, 2022. Accessed May 19, 2023. https://bit.ly/3OoCqg8}