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J2454 - A Phase 1, Multicenter, Open-Label, Dose Escalation, and Dose Expansion Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of DCSZ11 as a Monotherapy and in Combination in Patients with Advanced or

Details

Status

open

Study Type

Interventional

Study Phase

I

Location(s)

The Johns Hopkins Hospital

1800 Orleans St Baltimore, MD 21287

Brief Summary

This multi-center trial will be conducted worldwide. The overall time to participate in this study is 60 months. Participants will make multiple visits to the clinic, and survival follow-up for a maximum of up to 12 months after the last dose of the study drug.

The drug being tested in this study is called DCSZ11. DCSZ11 is being tested to treat people who have advanced or metastatic solid tumors. The study will include a dose escalation phase and a dose expansion phase.

The study will enroll approximately 138 patients in dose escalation, and approximately 113 participants in the dose expansion phase. Participants will receive escalating doses of DCSZ11 and a fixed dose of pembrolizumab until DCSZ11 doses for phase 1b are selected:

Phase 1a DCSZ11 monotherapy Dose Escalation. Phase 1a DCSZ11 in combination with fixed dose of pembrolizumab Dose Escalation. Once Phase 1b doses are selected for Phase 1b, participants of select advanced or metastatic solid tumors will receive DCSZ11 in below defined cohorts in Phase 1b:

Phase 1b cohort 1 NSCLC. Phase 1b cohort 2 Microsatellite Stable Colorectal Cancer (MSS-CRC) without liver involvement. Phase 1b cohort 3 MSS-CRC with liver involvement.

Eligibility

Inclusion Criteria: 1.Male or female patients ≥ 18 years of age. 2.Have a histologically or cytologically documented, advanced (metastatic and/or unresectable) solid tumor that has progressed on or after standard therapy (relapsed/refractory patients; patients must have failed at least one prior line of therapy) or for whom there is no effective standard therapy based on the Investigator's judgment. 3.At least 1 measurable lesion according to RECIST Version 1.1. 4. Patients must have a lesion that can be biopsied with acceptable clinical risk and agree to have a biopsy at Screening and on treatment. 5.Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.

Exclusion Criteria: 1.Received systemic anticancer treatments or investigational products within 14 days before the first dose of the study drug or 5 half-lives, whichever is shorter. 2.Received extended field radiotherapy ≤4 weeks before the start of treatment (≤7 days for limited field radiation for palliation outside the chest or brain). 3.Patients with second malignancy within the previous 3 years, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, cervical carcinoma in situ, resected colorectal adenomatous polyps, breast cancer in situ, or other malignancy for which the patient is not on active anticancer therapy. 4.Systemic arterial thrombotic or embolic events, such as cerebrovascular accident (including ischemic attacks) or hemoptysis within 3 months prior to the first dose of study drug. 5.Systemic venous thrombotic events (eg, deep vein thrombosis) or pulmonary arterial events (eg, pulmonary embolism) within 1 month prior to the first dose of study drug. Patients with venous thrombotic events prior to the first dose of study drug on stable anticoagulation therapy are eligible.