To Evaluate the Safety, Tolerability, Pharmacokinetics and Antitumor Activity of DAY301 in Participants With Locally Advanced or Metastatic Solid Tumors

Official title

A Phase 1, Open Label, Multiple Dose, Dose Escalation and Expansion Study to Investigate the Safety, Tolerability, Pharmacokinetics and Antitumor Activity of the PTK7-Targeted Antibody-drug Conjugate DAY301 in Patients With Locally Advanced or Metastatic Solid Tumors

Overview

This is a Phase 1a/1b, open-label, dose escalation and expansion study to evaluate the safety and anti-tumor activity of DAY301, a PTK7-directed antibody-drug conjugate (ADC) in participants with advanced or metastatic solid tumors. The study comprises of 2 phases: Phase 1a dose escalation where participants will be administered DAY301 at escalating dose levels to assess safety and tolerability, and to determine the maximum tolerated dose (MTD) and/or the recommended dose (RD); In Phase 1b dose expansion, DAY301 will be evaluated in dose expansion cohorts.

Interventions

• Drug DAY301
  DAY301 will be administered as IV infusion

Primary outcome measures

• Phase 1a: Dose Escalation: Number of participants with reported Dose Limiting Toxicities (DLTs) [Time frame: Within 21 days of first infusion (Day 1)]
• Phase 1a: Dose Escalation: Number of participants with reported adverse events (AEs) and serious AEs (SAEs) [Time frame: through the duration of treatment, up to approximately 12 months]
• Phase 1a: Dose Escalation: Frequency of dose interruptions [Time frame: through the duration of treatment, up to approximately 12 months]
• Phase 1a: Dose Escalation: Duration of dose interruptions [Time frame: through the duration of treatment, up to approximately 12 months]
• Phase 1a: Dose Escalation: Frequency of dose reductions [Time frame: through the duration of treatment, up to approximately 12 months]
• Phase 1a: Dose Escalation: Duration of dose reductions [Time frame: through the duration of treatment, up to approximately 12 months]
• Phase 1b: Dose Expansion: Objective response rate [Time frame: through the duration of treatment, up to approximately 12 months]
• Phase 1b: Dose Expansion: Number of participants reporting AEs and SAEs [Time frame: through the duration of treatment, up to approximately 12 months]
• Phase 1b: Dose Expansion: Frequency of dose interruptions [Time frame: through the duration of treatment, up to approximately 12 months]
• Phase 1b: Dose Expansion: Duration of dose interruption [Time frame: through the duration of treatment, up to approximately 12 months]

Secondary outcome measures (11)

• Phase 1a and Phase 1b: Maximum concentration (Cmax) of DAY301 [Time frame: Varying timepoints through the duration of treatment, up to approximately 12 months]
• Phase 1a and Phase 1b: time to Cmax (Tmax) of DAY301 [Time frame: Varying timepoints through the duration of treatment, up to approximately 12 months]
• Phase 1a and Phase 1b: area under the curve (AUC) of DAY301 [Time frame: Varying timepoints through the duration of treatment, up to approximately 12 months]
• Phase 1a and Phase 1b: terminal half-life (t1/2) of DAY301 [Time frame: Varying timepoints through the duration of treatment, up to approximately 12 months]
• Phase 1a Dose Escalation: Objective response rate [Time frame: through the duration of treatment, up to approximately 12 months]
• Phase 1a and 1b: Clinical Benefit rate (CBR) [Time frame: through the duration of treatment, up to approximately 12 months]
• Phase 1a and 1b: duration of response (DOR) [Time frame: through the duration of treatment, up to approximately 12 months]
• Phase 1a and 1b: time to response (TTR) [Time frame: through the duration of treatment, up to approximately 12 months]
• Phase 1a and 1b: Progression-free survival [Time frame: through the duration of treatment, up to approximately 12 months]
• Phase 1b: Overall survival [Time frame: through the duration of treatment, up to approximately 12 months]
• Phase 1a and 1b: Number of participants with positive antidrug antibodies (ADAs) [Time frame: varying timepoints through the duration of treatment, up to approximately 12 months]

Eligibility criteria

Inclusion criteria

• Histologically or cytologically confirmed diagnosis of advanced or metastatic solid tumors of the following histologies:
• Ovarian cancer
• Esophageal squamous cell carcinoma
• Triple-negative breast cancer
• Non-small cell lung cancer
• Small cell lung cancer
• Head and neck squamous cell carcinoma
• Cervical squamous cell carcinoma
• Endometrial cancers

(Participants must have been previously treated with standard of care systemic therapy, have refused standard therapy, or have no standard therapy available).

• Availability of tumor tissue sample (either an archival specimen or a fresh biopsy) at screening
• Measurable disease per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate organ function.

Exclusion criteria

• Prior use of PTK7 targeting treatment (Phase 1a) or prior use of PTK7 targeting treatments and/or topoisomerase 1 (TOP1) inhibitors (Phase 1b).
• Phase 1b disease-specific exclusion criteria:

• Cohort 1: Neuroendocrine tumors or endometrial sarcoma (eg, stromal sarcoma, leiomyosarcoma, or other types of pure sarcomas)
• Cohort 2: Nasopharyngeal primary tumors.
• Cohort 3: Ovarian cancer that progressed >6 months after the last dose of platinum-based chemotherapy (platinum-sensitive disease), or disease that did not respond (PR or complete response \[CR\]) to or progressed ≤91 days after the last dose of first-line platinum-based chemotherapy (primary platinum-refractory disease) .- History of small bowel obstruction requiring hospitalization within 3 months prior to the first dose of study treatment.
• Ascites requiring frequent paracentesis (more often than approximately every 4 weeks) for symptomatic management, or new onset within 4 weeks prior to the first dose of study treatment. Patients with an indwelling catheter may be considered eligible, after consultation with the medical monitor.
• Active or progressing brain metastases or evidence of leptomeningeal disease.
• Persistent toxicities from previous systemic antineoplastic treatments of Grade >1, excluding alopecia and vitiligo.
• Systemic antineoplastic therapy within five half-lives or 4 weeks, whichever is shorter, prior to first dose of study treatment, including investigational agents.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 9 centers

• Site: 001-058 — New Haven
• Site: 001-064 — Sarasota
• Site: 001-060 — Avon
• Site: 001-059 — Grand Rapids
• Site: 001-039 — New York
• Site: 001-073 — Oklahoma City
• Site: 001-065 — Nashville
• Site: 001-069 — Houston
• … and 1 more center

Canada · 2 centers

• Site: 011-013 — Vancouver
• Site: 011-005 — Toronto

Identifiers

NCT: NCT06752681 · DAY301-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗