Givastomig Earns FDA Fast Track Designation in HER2-Negative Gastric Cancer

The FDA has granted fast track designation to givastomig (TJ033721/ABL111) in combination with nivolumab (Opdivo) and chemotherapy for the treatment of patients with previously untreated HER2-negative advanced or metastatic gastroesophageal adenocarcinoma (GEA) whose tumors are both Claudin 18.2 (CLDN18.2) and PD-L1 positive, according to a news release from the developer, NovaBridge Biosciences.¹

The designation applies to givastomig, a CLDN18.2 x 4-1BB bispecific antibody, which the company is developing as both a potential first-in-class and best-in-class agent in this biomarker-defined population. A registrational phase 3 trial is expected to begin as early as the fourth quarter of 2026, and detailed phase 1b data are expected to be presented at a major medical conference in the second half of 2026.

“Fast track designation is a valuable step forward for givastomig and for patients with first-line HER2-negative metastatic gastric cancer,” said Phillip Dennis, MD, PhD, chief medical officer of NovaBridge, in the press release.¹ “Phase 1b results demonstrate robust efficacy and favorable overall tolerability in combination with immunochemotherapy. Responses were deep and durable across a broad patient population, with marked improvement relative to historical benchmarks for the standard of care.”

What phase 1b data support givastomig’s fast track designation?

Phase 1b dose expansion data from a multicenter, open-label study (NCT04900818) evaluating givastomig added to nivolumab and mFOLFOX6 (oxaliplatin, fluorouracil, and leucovorin) chemotherapy in patients with first-line HER2-negative, CLDN18.2-positive metastatic gastric cancer were previously shared in a press release.² They demonstrated an objective response rate (ORR) of 77% at the 8 mg/kg dose level (n = 20/26) and 73% at the 12 mg/kg dose level (n = 19/26). Responses were observed across a wide range of CLDN18.2 and PD-L1 expression levels, including in patients with low expression of either biomarker.

The median progression-free survival (PFS) was 16.9 months (95% CI, 6.8-not applicable [NA]) in the 8 mg/kg cohort and 7.7 months (95% CI, 6.9-NA) in the 12 mg/kg cohort. The 6-month PFS rates across both dose cohorts were 73% (95% CI, 51.7%-86.2%) and 91% (95% CI, 69.0%-97.7%), respectively.

The safety profile was comparable to standard-of-care immunochemotherapy regimens, with no dose-dependent increase in treatment-related adverse events (TRAEs). The most common TRAEs related to any drug were fatigue, nausea, and neutropenia, which were observed in most patients in each cohort. The only grade 4 TRAE was neutropenia, which occurred in 4% and 7% of the 8 and 12 mg/kg cohorts, respectively; no grade 5 TRAEs were reported.

Notably, immune-related gastritis occurred in 33% of patients in each cohort, including grade 3 instances in 4% of the 8 mg/kg cohort and 15% of the 12 mg/kg cohort. The investigators noted that gastritis was not observed in the phase 1 monotherapy study of givastomig, and that it commonly occurred after several cycles of therapy and was managed with medications and treatment interruption. It was also noted that those who experienced gastritis demonstrated improved ORR, PFS, and overall survival compared with those who did not develop gastritis.

What is the planned phase 3 trial design for givastomig?

“Fast track designation, combined with FDA’s prior confirmation of accelerated approval pathway eligibility, enables a more efficient path to a registrational phase 3 trial, reflecting givastomig’s promise as a first-in-class and best-in-class CLDN18.2-directed therapy for gastric cancer,” Dennis continued.¹ “We look forward to ongoing dialogue with the FDA to bring givastomig to patients as quickly as possible.”

Developers intend to initiate a registrational phase 3 combination trial as early as the fourth quarter of 2026, with ORR as the primary end point for a potential accelerated approval submission. Givastomig will be evaluated in combination with immunochemotherapy. Final study design details remain under discussion with the FDA. The company previously reported that the FDA confirmed givastomig’s eligibility for an accelerated approval pathway following a productive Type B meeting in March 2026.³ Fast track designation, combined with that earlier accelerated approval pathway confirmation, is intended to support a more efficient path to a phase 3 readout and potential regulatory submission.

What is givastomig and how does it work?

Givastomig is a bispecific antibody that simultaneously targets CLDN18.2-positive tumor cells and conditionally activates T cells through the 4-1BB signaling pathway within the tumor microenvironment. This mechanism is designed to drive antitumor T cell activity specifically where CLDN18.2 is expressed while limiting the systemic 4-1BB–related toxicities associated with other agents in that class. In phase 1 trials, this conditional activation approach was associated with antitumor activity across a broad range of biomarker expression levels. Givastomig is also being evaluated in other CLDN18.2-positive gastrointestinal malignancies.

References

1. NovaBridge Biosciences receives FDA fast track designation for givastomig in first-line HER2-negative metastatic gastric cancer. News release. NovaBridge Biosciences. June 16, 2026. Accessed June 17, 2026. https://tinyurl.com/2jmw6psx
2. 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 June 17, 2026. https://tinyurl.com/mpt266fd
3. 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 June 17, 2026. https://tinyurl.com/4ejd978s