PYX-201 Generates Responses in Pretreated Advanced HNSCC and Other Solid Tumors

Head and neck cancer

Image credit: shahzaib–stock.adobe.com

Treatment with the novel antibody-drug conjugate PYX-201 led to responses in patients with previously treated advanced solid tumors, including head and neck squamous cell carcinoma (HNSCC), according to preliminary data from a phase 1 trial (NCT05720117).¹

Findings showed that patients with HNSCC (n = 6) who received PYX-201 at doses ranging from 3.6 mg/kg to 5.4 mg/kg experienced a confirmed overall response rate (ORR) of 50% per RECIST 1.1 criteria, which was comprised of 1 complete response and 2 partial responses. The disease control rate (DCR) was 100%.

In the trial’s overall efficacy-evaluable population (n = 31), the ORR was 26%. Confirmed and unconfirmed responses were also achieved by patients with ovarian cancer, non–small cell lung cancer (NSCLC), hormone receptor (HR)–positive/HER2-negative breast cancer, triple-negative breast cancer (TNBC), and sarcoma.

"These encouraging preliminary clinical data demonstrate the potential for PYX-201 to yield meaningful responses in heavily pretreated patients with head and neck cancer along with several additional solid tumor types," Glenn J. Hanna, MD, stated in a news release. "The patients in the study have endured multiple rounds of therapy before treatment with PYX-201. We believe the quantity and quality of the responses, including a complete response and PYX-201's tolerability profile, highlight its promising potential across multiple indications with high unmet medical need, particularly in head and neck cancer."

Hanna is the director of the Center for Cancer Therapeutic Innovation (Early Drug Development Program) and the Center for Salivary and Rare Head and Neck Cancers, at Dana-Farber Cancer Institute, and serves as an associate professor of medicine at Harvard Medical School, in Boston, Massachusetts.

PYX-201 is a first-in-concept ADC that features a microtubule inhibitor payload and is designed to target extradomain-B fibronectin (EDB+FN), which is a noncellular structural component in the tumor extracellular matrix.

The open-label, multicenter, dose-escalation phase 1 study is enrolling patients at least 18 years of age with advanced solid tumors who experience disease progression with standard therapy, are unsuitable for standard therapy, or do not have standard therapy available.² Eligible tumor types include NSCLC, breast cancer, HNSCC, ovarian cancer, thyroid cancer, pancreatic ductal adenocarcinoma, soft tissue sarcoma, hepatocellular carcinoma, and kidney cancer.

Other key inclusion criteria include measurable disease per RECIST 1.1 criteria; an ECOG performance status of 0 or 1; a life expectancy of more than 3 months; and adequate hematologic, renal, and liver function.

Investigators are excluding patients with untreated brain metastases; brain metastases requiring treatment; significant cardiovascular disease; and neuropathy higher than grade 1. Prior solid organ or bone marrow transplant is not permitted. Prior treatment with any EDB+FN–targeting therapy is not allowed.

During dose escalation, enrolled patients (n = 80) received intravenous PYX-201 at doses ranging from 0.3 mg/kg to 8.0 mg/kg.¹ The current identified dose range for the ADC is 3.6 mg/kg to 5.4 mg/kg.

Dose-limiting toxicities and safety serve as the trial’s primary end points.² Secondary end points include pharmacokinetics, ORR, duration of response, progression-free survival, DCR, time to response, and overall survival.

Enrolled patients received a median of 4 prior lines of therapy, and some patients were administered up to 10 prior lines of therapy.¹

Safety data demonstrated that PYX-201 was well tolerated. Treatment-related adverse effects (TRAEs) led to treatment discontinuation, interruption, or delay in small proportions of patients. In the news release, Pyxis Oncology noted that the low incidence of payload-related TRAEs underscores the “enhanced molecular stability and differential expression of EDB in tumor tissue with negligible expression in normal tissues.”

"PYX-201 is an innovative investigational therapy designed with a unique extracellular mechanism of action, unlike any other ADC currently on the market or in development. These initial clinical data, demonstrating tumor shrinkage across a broad range of solid tumors with a differentiated safety profile indicate a significant opportunity to further develop PYX-201 across a variety of tumor types in both the mono and combo therapy settings," Anthony Tolcher, MD, FRCPC, FACP, founder and chief executive officer of NEXT Oncology and PYX-201 study investigator, added in a news release. "Additionally, the encouraging safety data support the potential for PYX-201 to be safely combined with other agents, including checkpoint inhibitors, to drive further patient responses."

Pyxis Oncology intends to initiate expansion cohorts for patients with HNSCC. These cohorts will evaluate PYX-201 in combination with pembrolizumab (Keytruda) in the first- and second-line settings; as monotherapy in the second- and third-line settings for patients previously treated with platinum-based chemotherapy and a PD-1 inhibitor; and as monotherapy in patients previously exposed to EGFR and PD-1 inhibitors.

Expansion cohorts are also planned for patients with ovarian cancer, NSCLC, HR-positive/HER2-negative breast cancer, TNBC, and sarcoma.

References

1. Pyxis Oncology announces favorable preliminary PYX-201 clinical phase 1 part 1 data. News release. Pyxis Oncology. November 20, 2024. Accessed November 21, 2024. https://ir.pyxisoncology.com/news-releases/news-release-details/pyxis-oncology-announces-favorable-preliminary-pyx-201-clinical
2. Study of PYX-201 in solid tumors. ClinicalTrials.gov. Updated August 5, 2024. Accessed November 21, 2024. https://clinicaltrials.gov/study/NCT05720117