FDA Confirms Potential Accelerated Path for Givastomig in GE Cancer

A potential accelerated approval pathway has been confirmed by the FDA for givastomig (TJ033721/ABL111) for the treatment of gastric and gastroesophageal carcinoma.¹ Following a productive type B meeting, the FDA confirmed that the investigational Claudin (CLDN) 18.2 x 4-1BB bispecific antibody is eligible for an accelerated regulatory route in the first-line setting for patients whose tumors are HER2-negative (HER2–), CLDN18.2-positive, and PD-L1–positive.

The regulatory alignment follows the recent presentation of dose-expansion data from an ongoing phase 1b trial (NCT04900818), the first-in-human study of givastomig evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and early antitumor activity of the agent as monotherapy and combination therapy in advanced solid tumors.²

“We are thrilled to receive the positive feedback from FDA confirming givastomig’s eligibility for an accelerated approval pathway,” said Phillip Dennis, MD, PhD, chief medical officer of NovaBridge, sponsor of givastomig, in a news release.¹ “This important regulatory milestone builds on compelling phase 1b givastomig results that showed robust efficacy and favorable overall tolerability, with marked improvement relative to historical benchmarks for the standard of care in cross trial comparisons. Givastomig has the potential to be a first-in-class and best-in-class [CLDN]18.2 therapeutic for gastric cancer in combination with immunochemotherapy. We are looking forward to continuing our discussions with FDA and to bringing givastomig to patients as quickly as possible.”

Givastomig: Mechanism of Action and Rationale

Givastomig is designed to simultaneously target CLDN18.2 and 4-1BB. CLDN18.2 is a tight junction protein that is typically sequestered in normal gastric mucosa but becomes ectopically expressed and accessible on the surface of malignant cells in various gastrointestinal tumors.

The standard of care for advanced gastric and gastroesophageal cancer has shifted significantly with the emergence of biomarkers such as HER2, PD-L1, and most recently, CLDN18.2. In October 2024, the FDA approved zolbetuximab (Vyloy), the first monoclonal antibody targeting CLDN18.2, for use in combination with chemotherapy.² While zolbetuximab established CLDN18.2 as a validated therapeutic target, givastomig represents a next-generation approach by adding a potent T-cell costimulatory component via the 4-1BB pathway.¹

The drug’s mechanism utilizes "conditional activation," meaning the 4-1BB costimulatory signal is only triggered when the antibody is bound to CLDN18.2-positive tumor cells. This approach aims to concentrate T-cell activation within the tumor microenvironment (TME), thereby enhancing antitumor immunity while mitigating the systemic immune-related adverse events that have historically limited the development of 4-1BB monoclonal antibodies. By combining this targeted costimulation with standard-of-care PD-1 inhibition and chemotherapy, givastomig seeks to overcome the immunosuppressive TME characteristic of advanced gastric cancer.

Phase 1b Design and Clinical Data

The phase 1b study is enrolling up to 330 patients across sites in the US and China.³ The trial consists of 4 parts, each part testing various givastomig treatment regimens in different patient populations:

1. Part 1: Givastomig monotherapy in patients with advanced or metastatic solid tumors.
2. Part 2: Givastomig in combination with nivolumab (Opdivo) and modified FOLFOX6 chemotherapy in treatment-naive patients with unresectable, locally advanced or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma.
3. Part 3: Givastomig in combination with chemotherapy in patients with unresectable, locally advanced or metastatic pancreatic adenocarcinoma.
4. Part 4: Givastomig in combination with durvalumab (Imfinzi) and chemotherapy in patients with unresectable, locally advanced or metastatic biliary tract cancer.

Givastomig, dosed at 8 mg/kg and 12 mg/kg, plus immunochemotherapy demonstrated robust efficacy and manageable safety in part 2 of the study. Among 52 efficacy-evaluable patients, the objective response rate (ORR) was 75%, with an even higher ORR observed at the 8-mg/kg dose (77%).⁴ Responses were observed across a range of PD-L1 and CLDN18.2 expression levels.

Additionally, of 53 patients evaluable for progression-free survival (PFS), the median PFS was 16.9 months, with a 6-month landmark PFS of 82%.

Givastomig combination therapy was also well tolerated by patients at both 8-mg/kg and 12-mg/kg dose levels, with a safety profile comparable to that of the current standard of care and no dose-dependent toxicities.

Future Development and Registrational Plans

As next steps, the sponsor expects to initiate a registrational phase 3 trial of givastomig as early as the fourth quarter of 2026. This trial will evaluate the efficacy and safety givastomig in combination with immunochemotherapy, with ORR as a primary end point to support accelerated approval.¹ Final study design details will be discussed with the FDA, according to the sponsor.

REFERENCES

1. NovaBridge announces productive FDA Type B meeting on potential accelerated approval pathway for givastomig in gastric cancer. News release. NovaBridge Biosciences. March 16, 2026. Accessed March 16, 2026. https://tinyurl.com/yeynwwnh

2. Astellas' VYLOY™ (zolbetuximab-clzb) approved by U.S. FDA for treatment of advanced gastric and GEJ cancer. News release. Astellas. October 18, 2024. Accessed March 16, 2026. https://bit.ly/3Nu7SYC

3. Study of TJ033721 (givastomig) in subjects with advanced or metastatic solid tumors. ClinicalTrials.gov. Updated March 5, 2026. Accessed March 16, 2026. https://clinicaltrials.gov/study/NCT04900818

4. NovaBridge presents positive givastomig dose expansion data from the phase 1b combination study in patients with 1L metastatic gastric cancer. News release. NovaBridge Biosciences. January 6, 2026. Accessed March 16, 2026. https://tinyurl.com/mud34n67