A Study of PYX-201 in Advanced Solid Tumors

Inclusion

• 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.

Exclusion

• 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 keratopathy
• Participants 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.