A First-in-Human, Open-label, Multicenter, Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of PYX-201 in Participants With Advanced Solid Tumors
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Study Summary
To evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, anti-tumor activity and preliminary efficacy in patients with solid tumors known to have significant expression of EDB of fibronectin. To determine the recommended phase 2 dose. 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. To assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of MICVO in participants (pts) with select advanced solid tumors. Circulating tumor DNA (ctDNA) was evaluated as a pharmacodynamic biomarker in response to MICVO.
Part 2 will evaluate participants in tumor specific cohorts with locally advanced, unresectable, and/or metastatic solid tumors at the recommended dose for expansion, 5.4 mg/kg IV every 3 weeks.
The ongoing MICVO Phase 1 monotherapy study is a two-part study. Part 1 was a dose escalation study across multiple doses and tumor types. Part 2, a dose expansion study at 5.4 mg/kg IV Q3W in 2L+ R/M HNSCC.
- Histologically or cytologically confirmed solid tumors including locally advanced/metastatic HR+ and HER2- breast cancer (post CDK4/6 inhibitor +/- ET, ≤ 2 lines systemic therapy), TNBC (1-3 prior lines including post ADC topo-1 payload), HNSCC (1-2 prior lines including post PD-L1/PD1 and platinum based therapy), and other solid tumor types (≤ 2 lines systemic therapy).Male or non-pregnant, non-lactating female participants age ≥18 years.Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 1.Participant must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.Life expectancy of >3 months, in the opinion of the Investigator.Corrected QTcF <470 msec.Adequate hematologic function.Adequate hepatic function.Adequate renal function.Adequate coagulation profile.Clinical sites must conduct fresh tumor biopsy or provide participant's archived tumor tissue sample.
- ESMO 2025:
- The population for expansion includes pts with recurrent and/or metastatic HNSCC in two cohorts including pts who have received at least 1 but no more than 2 lines of prior systemic therapy including a platinum-based therapy and a PD-1 inhibitor (Cohort A1) and pts who have received up to 2L of prior systemic therapy that must include 1 PD-1 and 1 EGFR directed treatment (Cohort A2).
- History of another malignancy except for the following: adequately treated local basal cell or squamous cell carcinoma of the skin; in situ cervical carcinoma; adequately treated, noninvasive bladder cancer.Known symptomatic brain metastases.Significant cardiovascular disease within 6 months prior to start of study drug.Evidence of an active systemic bacterial, fungal, or viral infection requiring treatment at the start of study drug.Known active hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS).Failure to recover to baseline severity or Grade ≤1 NCI-CTCAE v5.0 from acute non-hematologic toxicity.Participants with NCI-CTCAE v5.0 Grade >1 neuropathy of any etiology.Prior solid organ or bone marrow progenitor cell transplantation.Prior high-dose chemotherapy requiring stem cell rescue.Received systemic anticancer therapy within 28 days or within 5 half-lives (whichever is shorter) prior to the start of study drug.Palliative radiation therapy within 14 days prior to the start of study drug.Previously received extra domain B splice variant of fibronectin (EDB+FN) targeting treatments at any time prior to the start of PYX-201 treatment.History of uncontrolled diabetes mellitus.History of Stevens-Johnson syndrome or toxic epidermal necrolysis.Participants with corneal epithelial disease, with the exception of mild punctate keratopathyParticipants with the best-corrected visual acuity in the worst-seeing eye worse than 20/100 (Snellen equivalent).Participants with a history of (noninfectious) pneumonitis/ interstitial lung disease that required steroids, has current pneumonitis/ interstitial lung disease, or evidence of active pneumonitis on screening chest CT scan or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
Clinical Study Information for Healthcare Providers
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