On November 20, 2024 Pyxis Oncology, Inc. (Nasdaq: PYXS), a clinical stage company focused on developing next generation therapeutics to target difficult-to-treat cancers, reported positive preliminary data from the ongoing Phase 1 clinical dose escalation study evaluating PYX-201 in multiple types of solid tumors (Press release, Pyxis Oncology, NOV 20, 2024, View Source [SID1234648523]). PYX-201, the Company’s lead clinical drug candidate, is a first-in-concept antibody-drug conjugate (ADC) with a microtubule inhibitor (optimized auristatin) payload that uniquely targets Extradomain-B Fibronectin (EDB+FN), a non-cellular structural component within the tumor extracellular matrix (ECM).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"These positive data represent a significant milestone for Pyxis Oncology as our novel ECM-targeting ADC, PYX-201, has demonstrated clinical responses by RECIST 1.1 in six tumor types of interest: HNSCC, ovarian, NSCLC, HR+/HER2- breast, TNBC, and Sarcoma. The breadth and depth of our clinical responses clearly indicate the potential of PYX-201 to provide meaningful clinical benefits to patients with difficult-to-treat cancers," said Lara S. Sullivan, M.D., President and Chief Executive Officer of Pyxis Oncology. "In addition to the monotherapy expansion studies we are launching in 1Q25 in HNSCC, I am thrilled to announce our new Clinical Trial Collaboration Agreement with Merck (known as MSD outside of the US and Canada) to evaluate the combination of PYX-201 and Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab) in patients with HNSCC, HR+/HER2- breast, TNBC and Sarcoma with first patients expected to dose in 1Q25."
In this ongoing open-label, multicenter, dose-escalation Phase 1 trial of PYX-201, 80 patients have been enrolled and dosed across multiple solid tumor types to receive doses of PYX-201 ranging from 0.3 mg/kg up to 8.0 mg/kg. The trial’s main objectives are to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of PYX-201. The current identified dose range for PYX-201 is 3.6 mg/kg to 5.4 mg/kg. The number of prior lines of cancer therapies for patients enrolled is a median of 4 lines and up to 10 lines in some patients. The data cutoff date for this data announcement was October 4, 2024.
Preliminary Phase 1 Clinical Response Data in Patients with Head and Neck Squamous Cell Carcinoma (HNSCC):
Significant clinical responses were observed in HNSCC. Among evaluable HNSCC patients treated at an identified dose range of PYX-201 from 3.6 – 5.4 mg/kg (n=6), a confirmed 50% objective response rate (ORR) was observed, including one confirmed complete response (CR) and two confirmed partial responses (PR) by RECIST 1.1.
"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," said Glenn J. Hanna, M.D., Director, Center for Cancer Therapeutic Innovation (Early Drug Development Program) and Center for Salivary and Rare Head and Neck Cancers at Dana-Farber Cancer Institute, and Associate Professor of Medicine, Harvard Medical School. "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."
Clinical Trial Collaboration Agreement with Merck’s KEYTRUDA (pembrolizumab)
The Company additionally announces that it has entered into a Clinical Trial Collaboration Agreement with Merck (known as MSD outside of the US and Canada), for a Pyxis Oncology-sponsored study of PYX-201 in combination with Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab) in patients with 1L and 2L head and neck squamous cell carcinoma (HNSCC), HR+/HER2- breast cancer, and triple-negative breast cancer (TNBC) and sarcoma.
KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Pyxis Oncology and Merck each retain all commercial rights to their respective compounds, including as monotherapy or as combination therapies.
PYX-201 Development Plans in Head and Neck Squamous Cell Carcinoma (HNSCC)
The Company expects to initiate the following HNSCC Phase 1 expansion studies:
•
PYX-201 and KEYTRUDA combination dose escalation and expansion study in 1L and 2L HNSCC with preliminary clinical data readout expected in the second half of 2025;
•
PYX-201 monotherapy study in 2L and 3L HNSCC patients who are platinum and PD-1 inhibitor experienced, with preliminary clinical data readout expected in the second half of 2025; and
•
PYX-201 monotherapy study in 2L and 3L HNSCC patients who are EGFR and PD-1 inhibitor experienced, with preliminary clinical data readout expected in first half of 2026.
Preliminary Phase 1 Clinical Response Data in Additional Solid Tumor Types:
Encouraging confirmed and unconfirmed responses were observed in five additional solid tumor types: ovarian cancer, non-small cell lung cancer (NSCLC), HR+/HER2- breast cancer, triple-negative breast cancer (TNBC), and sarcoma.
PYX-201 Development Plan in Additional Tumor Types
Exploratory PYX-201 Phase 1 monotherapy expansion cohorts are planned in ovarian cancer, NSCLC, HR+/HER2- breast cancer, TNBC, and sarcoma, with preliminary clinical data expected in the second half of 2025.
The Company also expects to initiate the following clinical combination studies:
•
PYX-201 and KEYTRUDA combination study in HR+/HER2- breast cancer, TNBC, and sarcoma with preliminary clinical data expected in the second half of 2025 and the first half of 2026.
•
Preclinical studies of PYX-201 in combination with other agents in ovarian cancer and NSCLC to commence in 2025 to be followed by clinical studies with preliminary clinical data expected in 2026.
Summary of Preliminary Phase 1 Safety and Pharmacokinetics (PK) Data:
PYX-201 demonstrated favorable preliminary tolerability profile data with low incidence of dose discontinuation, interruptions or delays due to treatment-related adverse events (TRAE). Low incidence of Grade 3 or Grade 4 payload-related TRAEs within the identified dose range reinforce PYX-201’s differentiated construct enabling enhanced molecular stability and differential expression of Extradomain-B (EDB) in tumor tissue with negligible expression in normal tissues. The low incidence of Grade 1 or Grade 2 adverse events points to an attractive safety, given that it has been well tolerated and suitable for both monotherapy and combination therapy development.
With respect to PK data, PYX-201 demonstrated increased stability in circulation, which we believe is due to its proprietary design of site-specific conjugation chemistry as compared to certain approved val-cit-monomethyl auristatin E (MMAE) ADCs with non-site-specific conjugation chemistry.
"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," said Anthony Tolcher, M.D., FRCPC, FACP, Founder and Chief Executive Officer of NEXT Oncology and PYX-201 Study Investigator. "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."
Additional details and analyses beyond what have been included in this press release will be presented during the Company’s preliminary PYX-201 Phase 1 data investor event today.
In-person and Virtual Investor Event Information
Pyxis Oncology will host a virtual and in-person investor event to discuss the preliminary Phase 1 data today, Wednesday, November 20, 2024, at 4:30 p.m. ET at Venue 42 by Convene, located at 5 Times Square in New York City. Anyone interested in attending the live event should RSVP to .
Pyxis Oncology’s members of executive management team will be joined by the following physician thought leaders to discuss preliminary data from the Phase 1 trial:
•
Anthony Tolcher, M.D., FRCPC, FACP, Founder and Chief Executive Officer, NEXT Oncology
•
Glenn J. Hanna, M.D., Director, Center for Cancer Therapeutic Innovation (Early Drug Development Program) and Center for Salivary and Rare Head and Neck Cancers at Dana-Farber Cancer Institute, and Associate Professor of Medicine, Harvard Medical School