Advanced Solid Tumors
Conditions
Keywords
EGFR, HER3, Bispecific Antibody-Drug Conjugate, Phase I, Advanced Solid Tumors
Brief summary
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
DRUGCS5007
CS5007 will be administered via intravenous (IV) infusion on Day 1 of repeated 21-day cycles (Q3W).
Sponsors
CStone Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| [Dose Escalation] Maximum tolerated dose (MTD) of CS5007 | Cycle 1 (Up to 21 Days) | Participants will receive CS5007 via intravenous (IV) infusion on Day 1 of repeated 21-day cycles (Q3W). The MTD will be determined, if any, by the number of participants who experience a dose limiting toxicity (DLT). |
| [Dose Escalation] Tentative recommended Phase II dose (RP2D) of CS5007 | Up to approximately 2 years | The selection of tentative RP2D will be based on consideration of overall safety information together with available pharmacokinetic, pharmacodynamic, and efficacy data. The tentative RP2D may be the MTD or a lower dose within the tolerable dose range. |
| [Dose Escalation] The incidence and severity of adverse events (AEs) | Up to approximately 2 years | — |
| [Dose Expansion] Objective response rate (ORR) evaluated by investigators per RECIST v1.1 | Up to approximately 2 years | — |
Secondary
| Measure | Time frame |
|---|---|
| [Dose Escalation & Expansion] Area under the curve (AUC) of CS5007 | Up to approximately 2 years |
| [Dose Escalation & Expansion] Maximum concentration (Cmax) of CS5007 | Up to approximately 2 years |
| [Dose Escalation & Expansion] Time to maximum concentration (Tmax) of CS5007 | Up to approximately 2 years |
| [Dose Escalation & Expansion] Elimination half-life (t1/2) of CS5007 | Up to approximately 2 years |
| [Dose Escalation & Expansion] Clearance (CL) of CS5007 | Up to approximately 2 years |
| [Dose Escalation & Expansion] Volume of distribution (Vz) of CS5007 | Up to approximately 2 years |
| [Dose Escalation & Expansion] Trough concentration (Ctrough) of CS5007 | Up to approximately 2 years |
| [Dose Escalation & Expansion] Accumulation ratio (R) of CS5007 | Up to approximately 2 years |
| [Dose Escalation & Expansion] Number of participants with anti-CS5007 antibodies | Up to approximately 2 years |
| [Dose Escalation] Objective response rate (ORR) evaluated by investigators per RECIST v1.1 | Up to approximately 2 years |
| [Dose Escalation & Expansion] Duration of response (DOR) evaluated by investigators per RECIST v1.1 | Up to approximately 2 years |
| [Dose Escalation & Expansion] Disease control rate (DCR) evaluated by investigators per RECIST v1.1 | Up to approximately 2 years |
| [Dose Expansion] The incidence and severity of adverse events (AEs) | Up to approximately 2 years |
Countries
Australia, China
Contacts
CONTACTSean Yao
Outcome results
None listed