A Phase I Study of CS5007 in Participants With Advanced Solid Tumors

Official title

A Phase I, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Anti Tumor Activities of CS5007, a Novel EGFR and HER3 Bispecific Antibody-Drug Conjugate, in Participants With Advanced Solid Tumors

Overview

This is a first-in-human (FIH), open-label, and multi-center Phase I study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of CS5007 as monotherapy in participants with advanced solid tumors. The study is comprised of a Phase Ia dose escalation and Phase Ib dose expansion.

Interventions

• Drug CS5007
  CS5007 will be administered via intravenous (IV) infusion on Day 1 of repeated 21-day cycles (Q3W).

Primary outcome measures

• [Dose Escalation] Maximum tolerated dose (MTD) of CS5007 [Time frame: Cycle 1 (Up to 21 Days)]
• [Dose Escalation] Tentative recommended Phase II dose (RP2D) of CS5007 [Time frame: Up to approximately 2 years]
• [Dose Escalation] The incidence and severity of adverse events (AEs) [Time frame: Up to approximately 2 years]
• [Dose Expansion] Objective response rate (ORR) evaluated by investigators per RECIST v1.1 [Time frame: Up to approximately 2 years]

Secondary outcome measures (12)

• [Dose Escalation & Expansion] Area under the curve (AUC) of CS5007 [Time frame: Up to approximately 2 years]
• [Dose Escalation & Expansion] Maximum concentration (Cmax) of CS5007 [Time frame: Up to approximately 2 years]
• [Dose Escalation & Expansion] Time to maximum concentration (Tmax) of CS5007 [Time frame: Up to approximately 2 years]
• [Dose Escalation & Expansion] Elimination half-life (t1/2) of CS5007 [Time frame: Up to approximately 2 years]
• [Dose Escalation & Expansion] Clearance (CL) of CS5007 [Time frame: Up to approximately 2 years]
• [Dose Escalation & Expansion] Volume of distribution (Vz) of CS5007 [Time frame: Up to approximately 2 years]
• [Dose Escalation & Expansion] Trough concentration (Ctrough) of CS5007 [Time frame: Up to approximately 2 years]
• [Dose Escalation & Expansion] Accumulation ratio (R) of CS5007 [Time frame: Up to approximately 2 years]
• [Dose Escalation & Expansion] Number of participants with anti-CS5007 antibodies [Time frame: Up to approximately 2 years]
• [Dose Escalation] Objective response rate (ORR) evaluated by investigators per RECIST v1.1 [Time frame: Up to approximately 2 years]
• [Dose Escalation & Expansion] Duration of response (DOR) evaluated by investigators per RECIST v1.1 [Time frame: Up to approximately 2 years]
• [Dose Escalation & Expansion] Disease control rate (DCR) evaluated by investigators per RECIST v1.1 [Time frame: Up to approximately 2 years]

Eligibility criteria

Inclusion criteria

• Evidence of a personally signed and dated informed consent document.
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
• Being ≥ 18 years of age on the day of signing informed consent.
• Pathologically or cytologically confirmed, unresectable advanced solid tumors.
• Participants must have at least one measurable lesion according to RECIST Version1.1.
• Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1.
• Adequate organ function.
• Life expectancy ≥ 3 months.
• Fertile men and women of childbearing potential must agree to use an effective method of birth control from providing signed consent and for 180 days after the last study drug administration

Exclusion criteria

• Has disease that is suitable for local treatment administered with curative intent.
• Has a history of a second malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured.
• Known primary central nervous system (CNS) tumor or solid tumor CNS metastasis that is symptomatic, untreated, or requires therapy.
• Has life-threatening bleeding event or severe bleeding within 3 months prior to first dose.
• Has uncontrolled pleural effusion, pericardial effusion, or ascites.
• Has immune deficient disease or received systemic immunosuppressive treatment.
• Has intestinal obstruction,or history of inflammatory bowel disease,or chronic diarrhea.
• Has history of (non-infectious) interstitial lung disease/pneumonitis that required steroids.
• Has active infections requiring systemic therapy.
• Has significant cardiovascular disease or cerebrovascular accident within specified timeframes prior to first dose.
• Insufficient washout from prior anti-tumor therapy.
• Received live vaccine within 28 days prior to first dose.
• History of allogeneic organ or hematopoietic stem cell transplantation.
• History of hypersensitivity to excipients of study drug or any monoclonal antibody.
• Any toxic effects of prior therapy unresolved to Grade ≤1.
• Active alcohol or drug abuse.
• Pregnant or breastfeeding women.
• Other acute or chronic medical or psychiatric conditions that may increase risk or interfere with study results, in the investigator's judgment.

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

Australia · 6 centers

• St Vincent's Hospital Sydney — Darlinghurst
• Macquarie University — North Ryde
• Calvary Mater Newcastle Hospital — Waratah
• Icon Cancer Centre South Brisbane — South Brisbane
• St Vincent's Hospital Melbourne — Fitzroy
• Linear Clinical Research Ltd — Nedlands

China · 1 center

• Shanghai Chest Hospital — Shanghai

Identifiers

NCT: NCT07622524 · CS5007-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗