The FDA has granted breakthrough therapy designation to JBS-003 (18F-fluoromisonidazole; FMISO), an investigational PET imaging tracer intended to identify tumor hypoxia and guide radiation de-escalation in patients with human papillomavirus (HPV)–positive oropharyngeal carcinoma.1
The tracer is licensed by Juniper Biosciences from Memorial Sloan Kettering Cancer Center, which was among the first to pioneer the clinical use of hypoxia for imaging in this setting.
JBS-003 is being evaluated in an ongoing phase 3 trial (NCT06563479), which is designed to determine whether FMISO PET–guided radiation can enable personalized chemoradiation approaches, with potentially lower doses of radiation.1,2 The trial is currently enrolling and has an estimated primary completion date in early 2028.1
“This [breakthrough therapy] designation is a powerful validation of what precision imaging can do for these patients. Using FMISO PET imaging, we can visualize the specific hypoxic signatures of a tumor to maintain aggressive control where it’s needed, while safely reducing radiation doses for patients with well-oxygenated tissue,” Alex Agnoletto, chief executive officer of Juniper Biosciences, stated in a news release. “The FDA has now recognized that this approach may represent a substantial improvement over the current standard of care. We are very excited to see future patients benefit from it.”
What does the phase 3 trial involve and who is eligible?
The phase 3 study, sponsored by Memorial Sloan Kettering Cancer Center, is a randomized, double-blind trial comparing FMISO PET–selected personalized chemoradiation vs standard chemoradiation in patients at least 18 years of age with HPV-positive oropharyngeal squamous cell carcinoma.2 Patients need to have tumors positive for both p16 expression and mRNA HPV by in situ hybridization. An ECOG performance status of 0 or 1 or a Karnofsky performance status of at least 70 is required, as well as adequate organ function.
The study is designed to enroll an estimated 291 patients who are being randomly assigned to personalized chemoradiation or standard chemoradiation. In the experimental arm, patients are receiving a single dose of JSB-003 at week 2 of radiation treatment. Patients in this arm who do not have evidence of hypoxia will receive radiation at 30 Gy given at 2 Gy per fraction, and those positive for hypoxia will continue with a standard 70-Gy dose, with both given in combination with chemotherapy. Those in the control arm are receiving standard-of-care chemoradiation.
FDA Breakthrough Therapy Designation for JSB-003
- The FDA granted Breakthrough Therapy Designation to JBS-003 (¹⁸F-fluoromisonidazole; FMISO), an investigational PET tracer that images tumor hypoxia to guide radiation de-escalation in HPV-positive oropharyngeal carcinoma.
- JBS-003 is being evaluated in the ongoing, randomized, double-blind phase 3 trial (NCT06563479), which is comparing FMISO PET–selected personalized chemoradiation with standard chemoradiation in an estimated 291 patients, with a primary end point of 2-year overall survival and estimated primary completion in early 2028.
- Pooled phase 2 data (n = 430) supporting the designation showed a 5-year OS rate of 97% whether patients received de-escalated 30-Gy or standard 70-Gy radiation, with hypoxia-negative patients treated at 30 Gy showing a lower distant-failure rate (1.3% vs 7.5%).
The primary end point is overall survival (OS) rate at 2 years.
“We are excited that the FDA has granted breakthrough therapy designation, and we look forward to completing this phase 3 trial and generating the pivotal evidence needed to support potential FDA approval,” Nancy Y. Lee, MD, FASTRO, a radiation oncologist and service chief for Head & Neck Oncology and Proton Therapy at Memorial Sloan Kettering Cancer Center, added in a news release.1
What prior data have been reported for JSB-003?
Pooled data from phase 2 trials (NCT03323463; NCT05491512) showed that among patients with HPV-positive oropharyngeal cancer treated using the hypoxia-guided strategy (n = 430), 75% had no evidence of intratumoral hypoxia on the treatment-time FMISO-PET scan and received radiation at 30 Gy, while 25% received 70 Gy.3
At a median follow-up of 4.05 years (range 1.27–10.03 years), the 5-year OS rate was 97% in both groups. The 5-year progression-free survival rate was 91% in the 30-Gy group and 89% in the 70-Gy group (P = .5). Local failure rates at 5 years were 2.2% vs 1.9%, respectively, while regional failure was 6.2% vs 3.9%, respectively. Patients with persistent hypoxia who received 70 Gy had a distant-failure rate of 7.5% compared with 1.3% among patients without hypoxia who received 30 Gy.
References
- Juniper’s JBS-003 (F-MISO) program receives FDA breakthrough therapy designation, advancing a first-in-class hypoxia tracer enabling radiation de-escalation in HPV-positive head and neck cancer. News release. Juniper Biosciences. September 1, 2026. Accessed September 1, 2026. https://juniperbiosci.com/junipers-jbs-003-receives-fda-breakthrough-therapy-designation-for-hpv-positive-head-neck-cancer/
- A study comparing personalized radiation therapy with standard radiation therapy in people with HPV-positive throat cancer. ClinicalTrials.gov. Updated July 28, 2026. Accessed September 1, 2026. https://clinicaltrials.gov/study/NCT06563479
- Lee NY, Sherman EJ, Schoder H, et al. Long-term outcomes of 18F-fluoromisonidazole positron emission tomography (FMISO PET)–guided major radiation dose de-escalation in HPV-associated oropharyngeal cancer: The 30 ROC approach. J Clin Oncol. 2026;44(suppl 16):103. doi:10.1200/JCO.2026.44.16_suppl.103
