CYNK-101 Gets FDA Fast Track Designation for HER2-Positive Gastric/GEJ Cancers

The FDA will speed up their review of CYNK-101 plus chemotherapy and immune checkpoint inhibitors for the treatment of advanced HER2-postivie gastric or gastroesophageal adenocarcinomas.

The novel drug combination of CYNK-101 plus standard frontline chemotherapy, Herceptin (trastuzumab) and Keytruda (pembrolizumab) for patients with advanced HER2-positive gastric or gastroesophageal (GEJ) adenocarcinoma was recently granted a fast track designation by the Food and Drug Administration (FDA), according to Celularity, the developer of CYNK-101.

Fast track designations speed up the process by which the FDA reviews a promising treatment. The goal is to quicker fill unmet needs in the treatment landscape for the patients who need them most.

CYNK-101 is manufactured from genetically modified human placental hematopoietic stem cells. In addition to innate natural killer (NK) cell functions to attack cancer, the therapy is meant to support antibody-dependent cellular cytotoxicity (ADCC) — another method of targeting cancer cells — when used in combination with other tumor-targeted monoclonal antibodies, in this case HER2-targeted Herceptin. Celularity received approval for an investigational new drug (IND) application for the allogeneic NK cell therapy in November 2021. A phase 1/2a study is currently being planned to test the safety and preliminary efficacy of the combination.

“We are extremely excited to receive this fast track designation and the support from the FDA for our investigational genetically modified NK cell therapy in the first-line setting of gastric/GEJ cancers," Dr. Robert Hariri, founder, chairperson, and chief executive officer of Celularity, said in a statement. "CYNK-101 is built on the foundation of our unique placental-derived source material, which as compared to other cell sources, has naturally enhanced proliferative potential (or “stemness”), that has been shown to be a determinant of persistence and efficacy potential. Using novel genetic engineering, we have enhanced the ability of CYNK-101 cells to synergize with approved antibodies and provide a novel and potentially non-cross resistant therapy to improve the lives of patients with G/GEJ cancers as well as a broad range of other indications.”

The new therapy would add to recent advances in the gastric/GEJ field. In May 2021, the FDA granted accelerated approval to the frontline combination of Keytruda, Herceptin and fluoropyrimidine- and platinum-containing chemotherapy for patients with HER2-positive gastric or GEJ adenocarcinoma.The approval was based on findings from the KEYNOTE-811 study, which was presented at the 2021 ASCO Annual Meeting shortly following the approval.

In the phase 3 study, overall response rate (percentage of patients whose disease responded to treatment; ORR) was 74.4% with the addition of Keytruda to standard therapy of chemotherapy and Herceptin. This was compared with 51.9% for standard therapy and placebo. The complete response rates were 11.3% with Keytruda vs 3.1% with placebo. The median duration of response was 10.6 months with the addition of Keytruda compared with 9.5 months in the placebo group.

“The addition of immune-based therapy of blocking PD-1 with a checkpoint inhibitor Keytruda to the prior standard of care (chemotherapy and Herceptin) has recently been shown to be of benefit in patients with first-line HER2/neu positive unresectable G/GEJ cancer,” Dr. Andrew Pecora, president of Celularity, said in a statement. “Our recently accepted IND enables the assessment to possibly further improve outcomes in gastric/GEJ treated with triple combination therapy by adding CYNK-101 cells."

The phase 1/2a study will assess the addition of CYNK-101 to the triplet combination after initial removal of tumors — a process known as cytoreduction. This approach could potentially limit resistance, Pecora noted. The goal with adding CYNK-101 to standard therapy will be to improve the depth and duration of response.

"(CYNK-101) is a potentially non-cross resistant therapy after initially cytoreducing the tumor mass and potentially diminishing resistance in the tumor microenvironment with combined chemotherapy, trastuzumab, and pembrolizumab induction followed by reinduction and maintenance with CYNK-101 cells in combination with trastuzumab and pembrolizumab,” Pecora noted. The full design of the study has not yet been revealed.

The fast track designation for CYNK-101 represents the third designation for Celularity, and the first for CYNK-101. In addition to genetically modified NK-cell therapy, Celularity has also received two fast track designations for CYNK-001, which is an unmodified NK-cell therapy. These designations were for the development of the therapy for acute myeloid leukemia and recurrent glioblastoma multiforme, a fast-growing and aggressive brain tumor.

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