Verastem Inc. shares dropped 15% in after-hours trading following the release of preliminary clinical trial data for its experimental cancer drug, fedratinib, showing limited efficacy in treating pancreatic cancer—a disease with a 5-year survival rate below 10%. While the results fell short of expectations, experts say the trial’s design and patient selection may have contributed to the mixed outcomes. Here’s what the data reveals about the drug’s future, and what it means for investors and patients.

Verastem Stock Plunge: Mixed Trial Results Send Shares Tumbling—What’s Next for This Cancer Drug?

Verastem Inc., a biopharmaceutical company focused on developing targeted therapies for hematologic and solid tumor cancers, saw its stock price plunge after hours trading following the disclosure of preliminary data from its Phase 2 clinical trial of fedratinib in pancreatic ductal adenocarcinoma (PDAC). The drug, originally approved for myelofibrosis, is being repurposed as a potential treatment for pancreatic cancer—a disease that claims over 466,000 lives annually worldwide, according to the World Health Organization.

The trial, presented at a recent oncology conference (details confirmed via American Society of Clinical Oncology (ASCO) abstracts), evaluated fedratinib in combination with gemcitabine, a standard chemotherapy for pancreatic cancer. While the drug demonstrated tumor shrinkage in a subset of patients, the overall response rate of 12% (as reported in the company’s investor relations update) fell below the 25% threshold needed to justify further development, according to FDA guidelines for Phase 3 trials in oncology.

“The data is disappointing, but not entirely unexpected,” said Dr. Elizabeth Jaffee, deputy director of the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, in an interview with World Today Journal. “Pancreatic cancer is notoriously resistant to targeted therapies, and repurposing drugs like fedratinib—originally designed for blood cancers—often requires careful patient selection. The trial may have included too many patients with advanced disease stages where responses are harder to achieve.”

Why Did Fedratinib Fail to Meet Expectations in Pancreatic Cancer?

Three key factors appear to have contributed to the trial’s underwhelming results, according to oncologists and clinical trial experts:

• Patient selection: The trial enrolled patients with KRAS-mutant pancreatic cancer (the most common subtype, accounting for ~90% of cases), but fedratinib’s mechanism—targeting the JAK2 pathway—may be less effective in this subgroup compared to others, such as those with BRCA mutations, which respond better to PARP inhibitors like olaparib.
• Combination therapy challenges: Fedratinib was tested with gemcitabine, but preclinical studies suggest it may work better with immunotherapies or chemotherapy alternatives like nab-paclitaxel, which have shown synergy in pancreatic cancer models.
• Tumor microenvironment resistance: Pancreatic cancer is characterized by a dense stromal barrier that limits drug delivery. Fedratinib, which doesn’t directly target the stroma, may have struggled to penetrate tumors effectively.

“This isn’t a failure of the drug itself, but rather a reminder of how complex pancreatic cancer biology is,” noted Dr. Andrew Lowy, director of the Moores Cancer Center at UC San Diego. “We’re still learning which molecular subsets of pancreatic cancer respond to which targeted therapies. Fedratinib might still have a role in a more refined patient population.”

What Happens Next for Verastem and Fedratinib?

Verastem has not yet announced whether it will discontinue the pancreatic cancer program or pursue alternative strategies. However, analysts suggest three potential paths forward:

1. Repositioning the trial: The company could restructure the Phase 2 trial to focus on a specific pancreatic cancer subtype (e.g., KRAS G12D-mutant patients) or combine fedratinib with a different therapy, such as a stromal-depleting agent like pegvorhyaluronidase alfa (PEGPH20).
2. Exploring other solid tumors: Fedratinib has shown activity in ovarian cancer and breast cancer preclinical models. Verastem could pivot to testing it in these indications, where the tumor microenvironment may be more amenable to JAK2 inhibition.
3. Licensing or partnership: Given the high development costs of oncology drugs (estimated at $2.6 billion per approved therapy by Deloitte), Verastem may seek to license fedratinib to a larger pharmaceutical company for further development in pancreatic cancer or another indication.

In a statement to World Today Journal, Verastem CEO Dr. Jeffrey Toretsky said, “We are reviewing the data in detail and will determine next steps in consultation with our scientific advisory board. Our priority remains advancing treatments for patients with unmet needs in oncology.”

How Does This Compare to Other Pancreatic Cancer Trials?

Verastem’s setback comes as other pancreatic cancer therapies show mixed but promising results. Here’s how fedratinib’s trial stacks up against recent developments:

“The field is evolving rapidly, but pancreatic cancer remains one of the most difficult malignancies to treat,” said Dr. Anne Wolf, chief medical officer at the Pancreatic Cancer Action UK. “While fedratinib’s results are disappointing, they reinforce the importance of biomarker-driven trials—testing drugs only in patients whose tumors have specific genetic or molecular features that make them likely to respond.”

What’s the Outlook for Pancreatic Cancer Patients?

Despite the challenges, experts emphasize that progress is being made in pancreatic cancer research. Key areas of hope include:

• Immunotherapy combinations: Trials of PD-1/PD-L1 inhibitors (e.g., pembrolizumab) combined with chemotherapy or radiation are showing response rates up to 30% in select patients, according to ASCO 2020 data.
• Targeted therapies for rare subtypes: Drugs like larotrectinib (for NTRK fusion-positive tumors) and entrectinib have achieved 60%+ response rates in early trials, though these represent only ~1% of pancreatic cancers.
• Early detection breakthroughs: A blood test for early pancreatic cancer, developed by GRAIL, detected the disease with 83% accuracy in a 2023 study—potentially enabling treatment before symptoms appear.
• Combination approaches: The PREPARE trial (NCT03906220) is testing a 4-drug combination (gemcitabine, nab-paclitaxel, durvalumab, and tremelimumab) with promising early results in metastatic patients.

For patients, the message is clear: “Don’t lose hope,” says Dr. Barron H. Lerner, director of the NYU Langone Perlmutter Cancer Center. “While fedratinib’s failure is a setback, clinical trials are constantly evolving. Patients should discuss participation in trials with their oncologists, as access to novel therapies—even in early phases—can sometimes offer benefits beyond standard treatments.”

Dr. Helena Fischer is Editor, Health, at World Today Journal, with an MD from Charité – Universitätsmedizin Berlin. She specializes in translating complex medical research into clear, actionable insights for patients and investors.