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
- Phase
- Phase 1
- Intervention
- DAY301
- Conditions
- Advanced or Metastatic Solid Tumors
- Sponsor
- Day One Biopharmaceuticals, Inc.
- Enrollment
- 254
- Locations
- 12
- Primary Endpoint
- Phase 1a: Dose Escalation: Number of participants with reported Dose Limiting Toxicities (DLTs)
- Status
- Recruiting
- Last Updated
- 6 months ago
Overview
Brief Summary
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 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.
Investigators
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
- •Gastric/gastroesophageal junction adenocarcinoma
- •Cervical squamous cell carcinoma
- •Endometrial cancers
Exclusion Criteria
- •Prior use of PTK7 targeting treatment (Phase 1a) or prior use of PTK7 targeting treatments and/or topoisomerase 1 (TOP1) inhibitor-based antibody-drug conjugate (ADC) (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: Ovarian cancer that progressed \>6 months after the last dose of platinum-based chemotherapy (platinum-sensitive disease), or disease that did not respond (partial response \[PR\] or complete response \[CR\]) to or progressed ≤91 days after the last dose of first-line platinum-based chemotherapy (primary platinum-refractory disease)
- •Cohort 3: nasopharyngeal primary tumors.
- •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.
Arms & Interventions
DAY301 intravenous (IV) infusion
DAY301 will be administered at different dose levels in dose escalation and at the RD in dose expansion cohorts.
Intervention: DAY301
Outcomes
Primary Outcomes
Phase 1a: Dose Escalation: Number of participants with reported Dose Limiting Toxicities (DLTs)
Time Frame: Within 21 days of first infusion (Day 1)
To evaluate adverse events (AEs) considered dose limiting toxicities that occur in the first cycle of treatment (within a DLT observation period).
Phase 1a: Dose Escalation: Number of participants with reported adverse events (AEs) or serious AEs (SAEs)
Time Frame: through the duration of treatment, up to approximately 12 months
The type, incidence, and severity of AEs and SAEs will be determined using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Phase 1a: Dose Escalation: Frequency of dose interruptions
Time Frame: through the duration of treatment, up to approximately 12 months
The frequency at which dose interruptions occur during dose-escalation
Phase 1a: Dose Escalation: Duration of dose interruptions
Time Frame: through the duration of treatment, up to approximately 12 months
The duration of dose interruptions that occur during dose-escalation.
Phase 1a: Dose Escalation: Frequency of dose reductions
Time Frame: through the duration of treatment, up to approximately 12 months
The frequency at which dose reductions occur during dose-escalation.
Phase 1a: Dose Escalation: Duration of dose reductions
Time Frame: through the duration of treatment, up to approximately 12 months
The duration of dose reductions that occur during dose-escalation.
Phase 1b: Dose Expansion: Objective response rate
Time Frame: through the duration of treatment, up to approximately 12 months-up
Objective response rate based on best overall response (BOR) will be assessed by investigators according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
Phase 1b: Dose Expansion: Number of participants reporting AEs and SAEs
Time Frame: through the duration of treatment, up to approximately 12 months
The type, incidence, and severity of AEs and SAEs will be determined using the NCI CTCAE v5.0.
Phase 1b: Dose Expansion: Frequency of dose interruptions
Time Frame: through the duration of treatment, up to approximately 12 months
The frequency at which dose interruptions occur during dose-expansion.
Phase 1b: Dose Expansion: Duration of dose interruption
Time Frame: through the duration of treatment, up to approximately 12 months
The duration of dose interruptions that occur during dose-expansion.
Phase 1b: Dose Expansion: Frequency of dose reductions
Time Frame: through the duration of treatment, up to approximately 12 months
The frequency at which dose reductions occur during dose-expansion.
Phase 1b: Dose Expansion: Duration of dose reductions
Time Frame: through the duration of treatment, up to approximately 12 months
The duration of dose reductions that occur during dose-expansion.
Secondary Outcomes
- Phase 1a and Phase 1b: Maximum concentration (Cmax) of DAY301(Varying timepoints through the duration of treatment, up to approximately 12 months)
- Phase 1a and Phase 1b: time to Cmax (Tmax) of DAY301(Varying timepoints through the duration of treatment, up to approximately 12 months)
- Phase 1a and Phase 1b: area under the curve (AUC) of DAY301(Varying timepoints through the duration of treatment, up to approximately 12 months)
- Phase 1a and Phase 1b: terminal half-life (t1/2) of DAY301(Varying timepoints through the duration of treatment, up to approximately 12 months)
- Phase 1a Dose Escalation: Objective response rate(through the duration of treatment, up to approximately 12 months)
- Phase 1a and 1b: Clinical Benefit rate (CBR)(through the duration of treatment, up to approximately 12 months)
- Phase 1a and 1b: duration of response (DOR)(through the duration of treatment, up to approximately 12 months)
- Phase 1a and 1b: time to response (TTR)(through the duration of treatment, up to approximately 12 months)
- Phase 1a and 1b: Progression-free survival(through the duration of treatment, up to approximately 12 months)
- Phase 1b: Overall survival(through the duration of treatment, up to approximately 12 months)
- Phase 1a and 1b: Number of participants with positive antidrug antibodies (ADAs)(varying timepoints through the duration of treatment, up to approximately 12 months)