FDA Grants Fast Track Designation to Spevatamig in Advanced and Metastatic Biliary Tract Carcinoma

The FDA has granted fast track designation to spevatamig (PT886) for the treatment of patients with advanced and metastatic biliary tract carcinoma.¹

Spevatamig is a first-in-class claudin 18.2 (CLDN18.2)/CD47 bispecific antibody currently being evaluated in phase 2 studies across multiple gastrointestinal cancers. Phanes Therapeutics, the developer of spevatamig, recently expanded a clinical trial collaboration with Merck to study the agent in combination with pembrolizumab (Keytruda) for the first-line treatment of patients with biliary tract cancer.

“Spevatamig has the potential to be a transformational treatment option for patients with biliary tract cancer,” Ming Wang, PhD, MBA, chief executive officer of Phanes, stated in a news release. “Following the successful completion of enrollment in our phase 2 clinical trial of spevatamig in combination with chemotherapy for the frontline treatment of metastatic pancreatic ductal adenocarcinoma [mPDAC], we are making significant progress in the phase 2 study of the molecule in biliary tract cancer.”

Spevatamig previously received FDA fast track designation for metastatic CLDN18.2-positive pancreatic adenocarcinoma in 2024 and FDA orphan drug designation for metastatic pancreatic cancer in 2022.

What is the mechanism of action of spevatamig?

Spevatamig is a native IgG-like bispecific antibody that targets CLDN18.2 and CD47. It is an innate immunity enhancer, an emerging class of immuno-oncology agents designed to activate innate immune cells, such as macrophages and dendritic cells, by blocking the CD47 “don’t eat me” signal on cancer cells.¹˒² When combined with chemotherapy, which induces “eat me” signals, the immune-activation and cancer-killing activity of the agent is expected to be further stimulated.² This mechanism is intended to complement immune checkpoint inhibitors and may be relevant for tumors that are less likely to respond to checkpoint inhibition.¹

The agent’s anti-CD47 arm was engineered to bind CD47 more avidly on cancer cells than on human red blood cells, a design intended to mitigate the hematologic toxicity associated with CD47-targeting agents.² Spevatamig was constructed using the company’s PACbody and SPECpair bispecific antibody technology platforms. As of a data cutoff of May 14, 2026, 193 patients had been dosed with the agent globally across monotherapy and combination settings.

How is spevatamig being evaluated in biliary tract carcinoma?

The fast track designation follows enrollment in the phase 1/2 TWINPEAK study (NCT05482893), a first-in-human, open-label, multicohort trial evaluating spevatamig as monotherapy or in combination with chemotherapy and/or an immune checkpoint inhibitor in patients with advanced gastric, gastroesophageal junction, pancreatic ductal, or biliary tract carcinomas.³ The trial comprises phase 1 monotherapy dose-escalation followed by phase 2 combination expansion and dose-optimization cohorts.

Within the study, the biliary tract cancer cohort is enrolling patients with metastatic or advanced disease who have progressed on first-line standard-of-care (SOC) gemcitabine plus cisplatin with or without an immune checkpoint inhibitor and who are eligible for second-line SOC FOLFOX.

What data have been reported for spevatamig in gastrointestinal cancers?

The most mature clinical data for spevatamig come from the first-line mPDAC cohort of the TWINPEAK trial. Spevatamig at 2 mg/kg once weekly plus gemcitabine and nab-paclitaxel was evaluated in patients with treatment-naive mPDAC; in the 21-patient efficacy analysis set, 90.5% had de novo metastatic disease, a population consistent with those of pivotal first-line trials.² At data cutoff and a median follow-up of 8.9 months in the US and China populations, the combination elicited an objective response rate of 52.4% and a disease control rate of 90.5%. The median progression-free survival was 7.3 months, and the median overall survival (OS) was 14.7 months in the US analysis, with 67% of patients achieving an OS of at least 13.2 months.

The combination was deemed well tolerated in patients with mPDAC, with no significant additive toxicity to gemcitabine and nab-paclitaxel and no cytokine release syndrome observed at the evaluated dose levels. Grade 3 or higher treatment-emergent adverse effects reflected known chemotherapy class effects, including neutropenia and anemia. Data for the 3-mg/kg spevatamig dose level remain immature, however, the currently available TWINPEAK results support further development of spevatamig plus chemotherapy in a randomized phase 3 trial in patients with first-line mPDAC.

References

1. Phanes Therapeutics receives FDA fast track designation for spevatamig in advanced and metastatic biliary tract carcinoma. News release. Phanes Therapeutics, Inc. August 14, 2026. Accessed August 14, 2026. https://www.prnewswire.com/news-releases/phanes-therapeutics-receives-fda-fast-track-designation-for-spevatamig-in-advanced-and-metastatic-biliary-tract-carcinoma-302851460.html
2. Saeed A, Xu RH, Singh H, et al. Spevatamig (PT886), a claudin 18.2 (CLDN18.2)/CD47 bispecific antibody, in combination with gemcitabine plus nab-paclitaxel (GnP) in frontline (1L) treatment of metastatic pancreatic ductal adenocarcinoma (mPDAC). J Clin Oncol. 2026;44(suppl 16):4192. doi:10.1200/JCO.2026.44.16_suppl.4192
3. Spevatamig (PT886) as monotherapy or in combination with chemo and/or ICI, for the treatment of patients with advanced gastric, gastroesophageal junction, pancreatic ductal or biliary tract carcinomas (the TWINPEAK study). ClinicalTrials.gov. Updated July 9, 2026. Accessed August 14, 2026. https://clinicaltrials.gov/study/NCT05482893