FDA Grants Fast Track Designation to PYX-201 for Recurrent/Metastatic HNSCC

The FDA has granted fast track designation to PYX-201 for the treatment of adult patients with recurrent or metastatic head and neck squamous cell carcinoma (recurrent/metastatic HNSCC) whose disease has progressed following treatment with platinum-based chemotherapy and an anti–PD-(L)1 antibody.1

“Receiving fast track designation for PYX-201 from the FDA marks a significant milestone for Pyxis Oncology, recognizing our potential to address the significant medical need in recurrent/metastatic HNSCC. This designation underscores the urgency of bringing differentiated treatment options to patients and will help accelerate the development of PYX-201 as we actively recruit patients for our trial,” Lara S. Sullivan, MD, president and chief executive officer of Pyxis Oncology, stated in a news release. “We look forward to working with the FDA to advance this promising therapy as efficiently as possible.”

PYX-201 is a first-in-concept antibody-drug conjugate with a microtubule inhibitor payload that targets Extradomain-B Fibronectin (EDB+FN), a noncellular structural component within the tumor extracellular matrix, which is highly expressed in malignant tumors.

The agent is under evaluation in 2 early phase trials: the phase 1 PYX-201-101 trial (NCT05720117) and the phase 1/2 PYX-201-102 trial (NCT06795412).2 PYX-201-101 is an dose-escalation and -expansion study evaluating the agent as monotherapy in patients with recurrent/metastatic HNSCC predicted to express EDB+FN. PYX-201-102 is an open-label, global, multicenter, dose-escalation and -expansion study evaluating the agent in combination with pembrolizumab (Keytruda) in patients with recurrent/metastatic HNSCC and other advanced solid tumors. The company noted that this combination trial is part of a recently announced Clinical Trial Collaboration Agreement with Merck.

In November 2024, Pyxis Oncology announced favorable data from the phase 1 trial cohort of patients with HNSCC.3 At a data cutoff date of October 4, 2024, evaluable patients with HNSCC who received between 3.6 and 5.4 mg/kg of PYX-201 (n = 6), which is the current identified dose range, achieved a confirmed objective response rate (ORR) of 50%. This included 1 confirmed complete response and 2 confirmed partial responses by RECIST 1.1 criteria. The agent was also found to be generally well-tolerated, with a favorable safety profile.

By February 2025, the company had announced that the part 2 monotherapy expansion cohorts of the ongoing trial had begun to enroll patients.2 The expansion phase will evaluate the agent as second- and third-line therapy for patients with recurrent/metastatic HNSCC who have received prior platinum and PD-1 inhibitor therapy as well as those who have received prior EGFR and PD-1 inhibitor therapy.

In the same announcement, the company stated that the combination study was open to enrollment and would be evaluating the regimen across several indications, including recurrent/metastatic HNSCC in the first and second line; hormone receptor–positive and HER2-negative breast cancer; advanced or metastatic triple-negative breast cancer; gastric cancer; and cervical cancer.

In addition to ORR, the phase 1 monotherapy trial is evaluating the number of patients who experience a dose-limiting toxicity (DLT) and an adverse effect (AE).4 Key secondary end points include pharmacokinetics, duration of response, progression-free survival, overall survival, and disease control rate. In the phase 1/2 combination trial, the primary outcome measures include the number of patients who experience a DLT, AE, clinically significant change in clinical laboratory parameters, vital signs, and electrocardiogram parameters.5

References

1. Pyxis Oncology granted FDA fast track designation for PYX-201 monotherapy in patients with recurrent or metastatic head and neck cancer. News release. Pyxis Oncology. February 26, 2025. Accessed February 27, 2025. https://ir.pyxisoncology.com/news-releases/news-release-details/pyxis-oncology-granted-fda-fast-track-designation-pyx-201
2. Pyxis Oncology initiates new PYX-201 combination trial and initiates cohort expansions of ongoing monotherapy trial. News release. Pyxis Oncology. February 4, 2025. Accessed February 27, 2025. https://ir.pyxisoncology.com/news-releases/news-release-details/pyxis-oncology-initiates-new-pyx-201-combination-trial-and
3. Pyxis Oncology announces favorable preliminary PYX-201 clinical phase 1 part 1 data. News release. Pyxis Oncology. November 20, 2024. Accessed February 27, 2025. https://ir.pyxisoncology.com/news-releases/news-release-details/pyxis-oncology-announces-favorable-preliminary-pyx-201-clinical
4. Study of PYX-201 in solid tumors. ClinicalTrials.gov. Updated February 6, 2025. Accessed February 27, 2025. https://clinicaltrials.gov/study/NCT05720117
5. Study of PYX-201 in combination with pembrolizumab in advanced solid tumors. ClinicalTrials.gov. Updated January 28, 2025. Accessed February 27, 2025. https://clinicaltrials.gov/study/NCT06795412?term=NCT06795412&rank=1