A Phase I/II, 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, as Monotherapy and Combination Therapy in Participants With Advanced Solid Tumors

Study Identifier:
CS2009-101
CT.gov Identifier:
NCT06741644
EudraCT Identifier:
N/A
EU Trial (CTIS) Number:
N/A
Study Contact Information:
(210) 593-5651 or [email protected]
Recruiting

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Study 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. Phase Ia part (dose escalation of CS2009), to evaluate the safety and tolerability of CS2009; to determine the maximum tolerated dose (MTD, if any) and the provisional recommended phase II dose (RP2D) of CS2009 Phase Ib part (dose expansion of CS2009), to evaluate the efficacy of CS2009 in selected patients with advanced malignancies according to RECIST v1.1 The Phase Ib/II study comprises dose expansion and pivotal extension, assessing safety, tolerability, PK, and efficacy through multiple parallel cohorts investigating both monotherapy and combination regimens across various solid tumors. This trial will thoroughly evaluate the clinical potential of CS2009 in a wide range of advanced solid tumors, including but not limited to non-small cell lung cancer, hepatocellular carcinoma, gastric adenocarcinoma, endometrial cancer, ovarian cancer, renal cell carcinoma, colorectal cancer, and cervical cancer The multi-cohort expansion trial will evaluate CS2009 monotherapy and combination regimens across 15 cohorts covering multiple solid tumor indications: Non-Small Cell Lung Cancer (NSCLC): Monotherapy in treatment-naïve PD-L1 positive (tumor proportion score [TPS]≥1%), actionable genomic alterations (AGA) negative patients; Combination with chemotherapy in first-line non-squamous AGA negative patients; Combination with chemotherapy in first-line squamous AGA negative patients; Combination with chemotherapy in second-line PD-(L)1 refractory/resistant patients; Combination with chemotherapy for EGFR-mutant non-squamous patients after EGFR-TKI failure. - Hepatocellular Carcinoma (HCC): Monotherapy in unresectable advanced HCC after ≤2 prior systemic therapies. - Colorectal Cancer (CRC): Combination with chemotherapy in first-line proficient mismatch repair/microsatellite stable (pMMR/MSS) patients. - Platinum-Resistant Ovarian Cancer (PROC): Monotherapy after ≤2 lines post-platinum resistance; Combination with chemotherapy after ≤2 prior therapies. - Triple-Negative Breast Cancer (TNBC): Monotherapy after ≤2 prior therapies; Combination with chemotherapy in first-line setting. - Extensive-Stage SCLC (ES-SCLC): Combination with chemotherapy as first-line treatment. - Cervical Cancer (CC): Combination with chemotherapy as first-line treatment. - Gastric/Gastroesophageal Junction Cancer (GC/GEJC): Combination with chemotherapy as first-line treatment. - Esophageal Squamous Cell Carcinoma (ESCC): Combination with chemotherapy as first-line treatment.

To evaluate the efficacy and safety of CS2009 monotherapy and combination therapy across 15 cohorts in 9 solid tumor types, including NSCLC, CRC, extensive-stage small cell lung cancer (ES-SCLC), cervical cancer (CC), gastric or gastroesophageal junction cancer (GC/GEJC), esophageal squamous cell carcinoma (ESCC), platinum-resistant ovarian cancer (PROC), triple-negative breast cancer (TNBC), and hepatocellular carcinoma (HCC).

Safety was assessed in all treated pts. Efficacy was assessed in pts who had at least one post-baseline tumor assessment per RECIST v1.1.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Solid Tumor
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
Phase I/II
Sex
Female & Male
Age
18+ years
Study Drug
Drug: Drug: Cisplatin
Study Status
Indicates the current recruitment status or the expanded access status
Recruiting

Requirements information
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.
  • Phase I:
  • 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.
  • Phase II:
  • Pathologically or cytologically confirmed unresectable advanced solid tumors, including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), etc.
  • 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.
  • 1 I sign and date the Informed Consent Form indicating that the patient is informed of all matters related to this research study prior to undergoing any research specific procedures that are not part of the patient's routine care.
  • 2 Willing and able to comply with prescribed visits, treatment plans, laboratory tests, and other study procedures.
  • 3 The age was ≥ 18 years on the day of signing the informed consent.
  • 4 a) Unresectable advanced solid tumors confirmed by pathology or cytology. b) For advanced disease stage, standard treatment has failed, or there is no standard treatment available, or the patient is intolerant to standard treatment, or refuses standard treatment. Note: If disease relapse occurs during or ≤6 months after the end of adjuvant chemotherapy, adjuvant chemotherapy is considered to be the first-line systemic chemotherapy for the disease.
  • 5 Patients had at least one measurable lesion as defined by RECIST v1.1.
  • 6 The patients' Eastern Cooperative Oncology Group (ECOG) performance status was 0-1.
  • 7 Patients must have adequate organ function as shown by the following laboratory values (no blood transfusion, erythropoietin, granulocyte colony-stimulating factor, or other medical supportive therapy within 7 days before study drug administration).
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.
  • 1Have a disease that is amenable to local radical treatment.
  • 2A second active malignant disease within the past 3 years, except for locally curable cancers that have been completely cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
  • 3Known primary central nervous system (CNS) tumors or CNS metastases from solid tumors who are symptomatic, untreated, or require treatment.
  • 4Any active infection requiring systemic treatment within 2 weeks prior to the first dose of study drug.
  • 5Patients known to be human immunodeficiency virus (HIV) positive or with acquired immunodeficiency syndrome (AIDS).
  • 6Receipt of a live vaccine within 28 days before the first dose of study drug.
  • 7Patients who have used anti-tumor Chinese herbal preparations or Chinese patent medicines within 7 days before the first administration of study drug.
  • 8Patients who have used any other investigational drugs within 21 days before the first dose of study drug.
  • 9Pregnant or breastfeeding women.

Clinical Study Information for Healthcare Providers

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Study Locations

Location
Investigator
Status
Condition(s) Treated at Site
Location
START Los Angeles
Los Angeles, CA, United States, 90025
Investigator
Lasika Seneviratne
Status
Will Be Recruiting
Condition(s) Treated at Site
Solid Tumor