FDA Grants Fast Track Designation to CYNK-101 for HER2+ Gastric/GEJ Cancers


CYNK-101 plus standard frontline chemotherapy, trastuzumab, and pembrolizumab has received a fast track designation from the FDA for patients with advanced HER2-positive gastric or gastroesophageal junction adenocarcinoma.

The FDA has granted a fast track designation to CYNK-101 in combination with standard frontline chemotherapy, trastuzumab (Herceptin), and pembrolizumab (Keytruda) for patients with advanced HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma, according to Celularity, the developer of the genetically modified natural killer (NK) cell therapy.1

CYNK-101 is manufactured from human placental hematopoietic stem cells, which are genetically modified to express a high-affinity and cleavage-resistant CD16 variant (FCGRIIIA). In addition to innate NK cell functions, the therapy is meant to support antibody-dependent cellular cytotoxicity (ADCC) when used in combination with other tumor-targeted monoclonal antibodies, in this case HER2-targeted trastuzumab. 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," Robert Hariri, MD, PhD, 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 pembrolizumab, trastuzumab, and fluoropyrimidine- and platinum-containing chemotherapy for patients with HER2-positive gastric or GEJ adenocarcinoma.2 The approval was based on findings from the KEYNOTE-811 study, which was presented at the 2021 ASCO Annual Meeting shortly following the approval.3

In the phase 3 study, overall response rate (ORR) was 74.4% (95% CI, 66.2%-81.6%) with the addition of pembrolizumab to standard therapy of chemotherapy and trastuzumab. This was compared with 51.9% (95% CI, 43%-60.7%) for standard therapy and placebo (P = .00006). The complete response rates were 11.3% with pembrolizumab vs 3.1% with placebo. The median duration of response was 10.6 months with the addition of pembrolizumab compared with 9.5 months in the placebo group.

“The addition of immune-based therapy of blocking PD-1 with a checkpoint inhibitor (pembrolizumab) to the prior standard of care (chemotherapy and trastuzumab) has recently been shown to be of benefit in patients with first-line HER2/neu positive unresectable G/GEJ cancer,” Andrew Pecora, MD, 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 cytoreduction, this approach could potentially limit resistance, Pecora noted. CYNK-101 enhances ADCC, offers direct NK cell tumor killing, and helps T cell function and memory, he 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 2 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.


  1. Celularity receives fast track designation from U.S. FDA for its NK cell therapy CYNK-101 in development for the first-line treatment of advanced HER2/neu positive gastric and gastroesophageal junction cancers. News release. Celularity. January 18, 2022. Accessed January 18, 2022. https://bit.ly/3tyy3Vv
  2. Janjigian YY, Kawazoe A, Yanez PE, et al. Pembrolizumab plus trastuzumab and chemotherapy for HER2+ metastatic gastric or gastroesophageal junction (G/GEJ) cancer: initial findings of the global phase 3 KEYNOTE-811 study. J Clin Oncol. 2021;39(suppl 15):4013. doi:10.1200/JCO.2021.39.15_suppl.4013
  3. FDA grants accelerated approval to pembrolizumab for HER2-positive gastric cancer. News release. FDA. May 5, 2021. Accessed January 18, 2022. https://bit.ly/3yp08Ow.
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