Study of PYX-201 in Solid Tumors

Pyxis Oncology

Status and phase: Enrolling; Phase 1

Conditions: Solid Tumor; Advanced Solid Tumor

Treatments: Drug: PYX-201

Study type: Interventional

Funder types: Industry

Identifiers

NCT05720117

2023-509687-14-00 (EU Trial (CTIS) Number)

2022-002284-30 (EudraCT Number)

PYX-201-101

Details and patient eligibility

About

The primary objectives of this study are to determine the recommended dose(s) of PYX-201 for participants with relapsed/refractory (R/R) solid tumors, and to determine the objective response rate (ORR) in participants treated with PYX-201 as a single agent.

Enrollment: 330 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion

1. Histologically or cytologically confirmed solid tumors including locally advanced/metastatic NSCLC, HR+ and HER2- breast cancer, HR- and HER2-positive breast cancer, TNBC, HNSCC, ovarian cancer, thyroid cancer, pancreatic ductal adenocarcinoma (PDAC), sarcomas, hepatocellular carcinoma (HCC), kidney cancer, cervical cancer and endometrial cancer.
2. Male or non-pregnant, non-lactating female participants age ≥18 years.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 1.
4. Participant must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
5. Life expectancy of >3 months, in the opinion of the Investigator.
6. Corrected QTcF <470 msec.
7. Adequate hematologic function.
8. Adequate hepatic function.
9. Adequate renal function.
10. Adequate coagulation profile.
11. Clinical sites must conduct fresh tumor biopsy or provide participant's archived tumor tissue sample.

Exclusion

1. 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.
2. Known symptomatic brain metastases.
3. Significant cardiovascular disease within 6 months prior to start of study drug.
4. Evidence of an active systemic bacterial, fungal, or viral infection requiring treatment at the start of study drug.
5. Known active hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS).
6. Failure to recover to baseline severity or Grade ≤1 NCI-CTCAE v5.0 from acute non-hematologic toxicity.
7. Participants with NCI-CTCAE v5.0 Grade >1 neuropathy of any etiology.
8. Prior solid organ or bone marrow progenitor cell transplantation.
9. Prior high-dose chemotherapy requiring stem cell rescue.
10. Received systemic anticancer therapy within 28 days or within 5 half-lives (whichever is shorter) prior to the start of study drug.
11. Palliative radiation therapy within 14 days prior to the start of study drug.
12. Previously received extra domain B splice variant of fibronectin (EDB+FN) targeting treatments at any time prior to the start of PYX-201 treatment.
13. History of uncontrolled diabetes mellitus.
14. History of Stevens-Johnson syndrome or toxic epidermal necrolysis.
15. Participants with corneal epithelial disease, with the exception of mild punctate keratopathy
16. Participants with the best-corrected visual acuity in the worst-seeing eye worse than 20/100 (Snellen equivalent).

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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330 participants in 5 patient groups

Part 1: PYX-201 Dose Escalation

Experimental group

Description:

Participants will receive escalating doses of PYX-201 as an intravenous (IV) infusion to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and antitumor activity of PYX-201. Intra-participant dose escalation may be considered for participants who have adequately tolerated therapy.

Treatment:

Drug: PYX-201

Part 2: Cohort A

Experimental group

Description:

Participants with recurrent, persistent, and/or metastatic head and neck squamous cell carcinoma (HNSCC) who have received at least one but no more than two lines of prior systemic therapy, including platinum-based therapy and a programmed cell death protein 1 (PD-1) inhibitor, and participants who have received up to two lines of prior therapy that must include one prior PD-1 inhibitor and one prior epidermal growth factor receptor (EGFR)-directed treatment, will receive PYX-201 as an IV infusion at the recommended dose for Part 2.

Treatment:

Drug: PYX-201

Part 2: Cohort B

Experimental group

Description:

Participants with triple-negative breast cancer (TNBC) who have been treated with at least one but no more than two lines of prior systemic therapy will receive PYX-201 as an IV infusion at the recommended dose for Part 2.

Treatment:

Drug: PYX-201

Part 2: Cohort C

Experimental group

Description:

Participants with hormone receptor (HR)-positive (HR+)/human epidermal growth factor receptor 2 (HER2)-negative (immunohistochemistry \[IHC\] 0, IHC 1+, or IHC 2+/in situ hybridization \[ISH\]-negative) breast cancer who had progressed on cyclin-dependent kinase 4/6 (CDK-4/6) inhibitors plus endocrine therapy and one line of chemotherapy, and had received no more than three prior lines of systemic therapy, will receive PYX-201 as an IV infusion at the recommended dose for Part 2.

Treatment:

Drug: PYX-201

Part 2: Cohort D

Experimental group

Description:

Participants with various advanced solid tumor types, including non-small cell lung cancer (NSCLC), sarcomas, rare solid tumor head and neck (H\&N) cancers, ovarian cancer (OVCA), cervical cancer, and endometrial cancer, will receive PYX-201 as an IV infusion at the recommended dose for Part 2.

Treatment:

Drug: PYX-201