A Study of IDE034 in Adult Participants With Locally Advanced/Metastatic Solid Tumors Types

Official title

An Open-Label, Multicenter Study Evaluating the Safety, Efficacy, and Pharmacokinetics of IDE034 in Adult Participants With Locally Advanced/Metastatic Solid Tumors

Overview

This is a Phase 1a/1b, open-label, multicenter dose escalation and dose expansion clinical study to evaluate the safety, PK, immunogenicity and preliminary efficacy of IDE034 in participants with locally advanced/metastatic solid tumor types that express B7-H3 and PTK7.

Detailed description

Part 1 - Dose escalation Part 1 will evaluate increasing doses of IDE034 to assess safety, tolerability, and to determine dose-limiting toxicities (DLTs), the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) in subjects with locally advanced/metastatic solid tumor types that express B7-H3 and PTK7.

Part 2 - Dose Expansion Part 2 will evaluate participants with B7-H3 and PTK7 expressing advanced/metastatic solid tumors at 2 or more dose levels determined to be safe and tolerable during dose escalation. The goal of Part 2 is to identify which of the doses evaluated in Part 1 is safe, well tolerated and results in tumor responses.

In parallel a basket cohort may be enrolled at one of the expansion dose(s) for which the tumor types and other selection criteria will be based on emerging data from nonclinical and Part 1 clinical evaluations. Additional selection criteria may be applied to the expansion indications (e.g., histological subset or select molecular alterations) based on emerging data.

Interventions

• Drug IDE034
  IDE034

Primary outcome measures

• Safety and tolerability of IDE034 in Part 1 dose escalation [Time frame: 21 days following the first dose of IDE034]
• Safety and tolerability of IDE034 in Part 2 dose expansion [Time frame: Approximately 20 months total study duration]
• To evaluate preliminary anti-tumor activity of IDE034 in Part 2 dose expansion [Time frame: Time Frame: Approximately 20 months total study duration]
• To evaluate preliminary anti-tumor activity of IDE034 in Part 2 dose expansion [Time frame: Time Frame: Approximately 20 months total study duration]

Secondary outcome measures (12)

• To evaluate preliminary anti-tumor activity of IDE034 in Part 1 dose escalation [Time frame: Approximately 20 months total study duration]
• To evaluate preliminary anti-tumor activity of IDE034 in Part 1 dose escalation [Time frame: Approximately 20 months total study duration]
• To further characterize preliminary anti-tumor activity of IDE034 in Part 1 dose escalation [Time frame: Approximately 20 months total study duration]
• To further characterize preliminary anti-tumor activity of IDE034 in Part 1 dose escalation [Time frame: Approximately 20 months total study duration]
• To further characterize preliminary anti-tumor activity of IDE034 in Part 2 dose expansion [Time frame: Approximately 20 months total study duration]
• To further characterize preliminary anti-tumor activity of IDE034 in Part 2 dose expansion [Time frame: Approximately 20 months total study duration]
• Pharmacokinetics (PK) of IDE034 and its constituents: [Time frame: Approximately 20 months total study duration]
• Pharmacokinetics (PK) of IDE034 and its constituents [Time frame: Approximately 20 months total study duration]
• Pharmacokinetics (PK) of IDE034 and its constituents [Time frame: Approximately 20 months total study duration]
• Pharmacokinetics (PK) of IDE034 and its constituents [Time frame: Approximately 20 months total study duration]
• Pharmacokinetics (PK) of IDE034 and its constituents [Time frame: Approximately 20 months total study duration]
• To evaluate immunogenicity of IDE034 [Time frame: Approximately 20 months total study duration]

Eligibility criteria

Inclusion criteria

• Participant must be at least 18 years of age or the age of maturity per local regulations
• Participants with advanced recurrent or metastatic solid tumors expressing B7-H3 and PTK7 in the following indications: NSCLC, ESCC, endometrial cancer, HGSOC, HNSCC, TNBC (estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 \[HER2\] negative), CRC, and CRPC who have radiologically progressed or recurred on at least one line of therapy or is intolerant to additional effective standard therapies.
• Archival tissue sample for testing
• Measurable disease
• Have Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
• Have adequate bone marrow and organ function.
• Able to comply with contraceptive/barrier requirements

Exclusion criteria

• Known symptomatic brain metastases or leptomeningeal metastasis
• Known primary CNS malignancy and any other malignancies within 2 years prior to the first dose.
• Have uncontrolled tumor-associated pain
• Have clinically significant cardiac abnormalities and/or cerebrovascular disease (stroke) within 6 months before the first dose
• Active uncontrolled infection
• Have history of interstitial pneumonitis, current noninfectious pneumonitis requiring steroid therapy; known or suspected interstitial pneumonitis as seen on screening imaging; other moderate to severe lung diseases seriously affecting respiratory function within 3 months before the first dose.
• Have history of severe infections within 4 weeks prior to the start of study treatment, including but not limited to bacteremia, severe pneumonia, or other serious infectious complications requiring hospitalization.
• Have history of immunodeficiency, with a positive human immunodeficiency virus (HIV) test at screening.
• Participants with known or suspected viral hepatitis
• Have history of active tuberculosis within 1 year before enrollment
• If participants had adverse reactions to previous antitumor treatment that have not recovered to guidelines of CTCAE Grade ≤ 1 and Grade 2 peripheral neurological symptoms
• Have received chemotherapy within 3 weeks of first dose of IMP; immunotherapy or biologic targeted antitumor treatments within 3 weeks before the first dose of IMP or other investigational products within 4 weeks of first dose of IMP
• Administration of any of the following

• Current use or anticipated need for food or drugs that are known strong CYP3A4/5 inhibitors or inducers
• Have prior treatment with B7-H3 or PTK7 antibody-drug conjugate (ADC).
• Have prior treatment with a topoisomerase I inhibitor (TOP1i), including an ADC with a TOP1i payload, within 6 months of first dose of IMP
• Have received radiotherapy within 2 weeks prior to study entry
• Have undergone major surgery or trauma within 4 weeks prior to study entry.
• Have received live attenuated vaccine within 28 days prior to the first dose or are expected to receive live attenuated vaccine during the study treatment.
• Female participants who are pregnant, lactating, or planning to become pregnant during the study period to 7 months after the last dose of IMP.
• Are known to be allergic to any component or excipient of the IMP product or have a history of severe allergic reactions to other monoclonal antibody/fusion protein drugs.
• Participants with complications in the eye including ulcers in the eye, and severe dry eye

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

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 15 centers

• Sarah Cannon Research Institute at HealthONE — Denver
• Florida Cancer Specialists — Sarasota
• Karmanos Cancer Institute — Detroit
• START New York Long Island, LLC — Lake Success
• SCRI Oncology Partners — Nashville
• NEXT Texas LLC - Austin — Austin
• START Dallas Fort Worth, LLC — Fort Worth
• MD Anderson — Houston
• … and 7 more centers

Identifiers

NCT: NCT07503808 · IDE034-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗