Clinical trial NCT06741644: A Phase I Study of CS2009 in Participants With Advanced Solid Tumors
Official title: A Phase I, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Antitumor Activities of CS2009, a Tri-specific Antibody Targeting PD-1/VEGFA/CTLA-4, in Participants With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: PD-1
VEGFA
CTLA4
tri-specific antibody
advanced solid tumors
Phase I
Lead sponsor: CStone Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2024-12-19
Enrollment: 230
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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 CS2009 in participants with advanced solid tumors. The study is comprised of a Phase Ia dose escalation and Phase Ib dose expansion.


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.
* Age ≥ 18 years on the day of signing informed consent.
* Pathologically or cytologically confirmed, unresectable advanced solid tumors, including but not limited to non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), gastric cancer (GC), ovarian cancer (OC), cervical cancer (CC), etc.
* Failure of established standard of care for advanced disease, or no available standard of care, or intolerance to standard of care.
* Participants with at least one measurable lesion as defined per RECIST v1.1 solid tumor.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Adequate organ function.
* Fertile male participants and female participants of childbearing potential must be willing to use an effective method of birth control from providing signed consent and for 180 days after the last investigational product administration.
* Female participants of childbearing potential must have a negative pregnancy test ≤ 7 days prior to the first dose of the investigational product.

Exclusion Criteria:

* 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 either symptomatic, untreated, or requires therapy.
* Presence of uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage within 4 weeks prior to the first dose of investigational product.
* Receipt of systemic corticosteroid treatment or any other form of immune suppressing treatment within 7 days prior to the first dose of investigational product.
* Active or prior history of definite inflammatory bowel disease.
* History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, or presence of active or suspected ILD/pneumonitis.
* Active infections requiring systemic therapy within 2 weeks prior to the first dose of investigational product.
* Positive for human immunodeficiency virus (HIV) or presence of acquired immune deficiency syndrome (AIDS).
* Active Hepatitis B or C infection.
* Active pulmonary tuberculosis (TB).
* Major surgery, chemotherapy, definitive radiotherapy, target therapy, immunotherapy, or other anti-cancer therapy within 21 days prior to the first dose of investigational product.
* Palliative radiotherapy within 14 days prior to the first dose of investigational product, or receipt of radioactive drug within 56 days prior to the first dose of investigational product.
* Administration of live vaccine within 28 days prior to the first dose of investigational product.
* History of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
* Receipt of antitumor Chinese herbal preparations or Chinese patent medicine within 7 days prior to the first dose of investigational product.
* Receipt of any other investigational drugs within 21 days prior to the first dose in this trial.
* History of hypersensitivity or idiosyncrasy to the excipients of the study drug or any monoclonal antibody.
* Any toxic effects of prior therapy or surgical procedures unresolved to baseline severity or NCI-CTCAE Version 5.0 Grade ≤ 1.
* Active alcohol or drug abuse.
* Female participants who are pregnant or breastfeeding.
* Other acute or chronic medical or psychiatric conditions that may increase the risk associated with study participation or investigational product administration.

Primary outcomes:
measure: [Dose Escalation] Maximum tolerated dose (MTD) of CS2009
timeFrame: Cycle 1 (Up to 21 Days)
measure: [Dose Escalation] Tentative recommended Phase II dose (RP2D) of CS2009
timeFrame: Cycle 1 (Up to 21 Days)
measure: [Dose Escalation] Number of participants with adverse events (AEs)
timeFrame: Up to approximately 2 years
measure: [Dose Expansion] Objective response rate (ORR) evaluated by investigators per RECIST v1.1
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: [Dose Escalation & Expansion] Area under the curve (AUC) of CS2009
timeFrame: Up to approximately 2 years
measure: [Dose Escalation & Expansion] Maximum concentration (Cmax) of CS2009
timeFrame: Up to approximately 2 years
measure: [Dose Escalation & Expansion] Elimination half-life (t1/2) of CS2009
timeFrame: Up to approximately 2 years
measure: [Dose Escalation & Expansion] Minimum concentration (Cmin) of CS2009
timeFrame: Up to approximately 2 years
measure: [Dose Escalation & Expansion] Number of participants with anti-CS2009 antibodies
timeFrame: Up to approximately 2 years
measure: [Dose Escalation] Objective response rate (ORR) evaluated by investigators per RECIST v1.1
timeFrame: Up to approximately 2 years
measure: [Dose Expansion] Number of participants with adverse events (AEs)
timeFrame: Up to approximately 2 years
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Alfred Hospital (Alfred Health)
city: Melbourne
country: Australia
facility: Austin Hospital (Austin Health)
city: Melbourne
country: Australia
facility: Monash Medical Centre (Monash Health)
city: South Brisbane
country: Australia
facility: Icon Cancer Centre South Brisbane
city: Sydney
country: Australia
facility: Blacktown Hospital
city: Sydney
country: Australia
facility: Macquarie University Hospital
city: Sydney
country: Australia
facility: Scientia Clinical Research Ltd
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Changchun
country: China
facility: Jilin Cancer Hospital
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
city: Guangzhou
country: China
facility: Sun Yat-sen Memorial Hospital, Sun Yat-sen University
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
city: Hefei
country: China
facility: Anhui Provincial Hospital
city: Linyi
country: China
facility: Linyi Cancer Hospital
city: Shanghai
country: China
facility: Shanghai East Hospital
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
city: Xuzhou
country: China
facility: Xuzhou Central Hospital
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
Study officials:
References: