A Phase I/II Study of CS2009 in Participants With Advanced Solid Tumors

Official title

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

Overview

This is a first-in-human (FIH), open-label, and multi-center Phase I/II study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of CS2009 as Monotherapy and Combination Therapy in Participants with Advanced Solid Tumors. The study is comprised of a Phase I dose escalation and Phase II dose expansion.

Interventions

• Drug CS2009
  CS2009 will be administered via intravenous (IV) infusion on Day 1 of repeated 21-day cycles (Q3W).
• Drug CS2009
  CS2009 will be administered via intravenous (IV) infusion on Day 1 of repeated 14/21-day cycles (Q2W/Q3W).
• Drug Pemetrexed
  IV infusion
• Drug Carboplatin
  IV infusion
• Drug Paclitaxel
  IV infusion
• Drug Etoposide
  IV infusion
• Drug Nab-paclitaxel
  IV infusion
• Drug Oxaliplatin
  IV infusion
• Drug Capecitabine
  oral tablets
• Drug Docetaxel
  IV infusion

Primary outcome measures

• [Dose Escalation] Maximum tolerated dose (MTD) of CS2009 [Time frame: Cycle 1 (Up to 21 Days)]
• [Dose Escalation] Tentative recommended Phase II dose (RP2D) of CS2009 [Time frame: Cycle 1 (Up to 21 Days)]
• [Dose Escalation] Number of participants with 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 (7)

• [Dose Escalation & Expansion] Area under the curve (AUC) of CS2009 [Time frame: Up to approximately 2 years]
• [Dose Escalation & Expansion] Maximum concentration (Cmax) of CS2009 [Time frame: Up to approximately 2 years]
• [Dose Escalation & Expansion] Elimination half-life (t1/2) of CS2009 [Time frame: Up to approximately 2 years]
• [Dose Escalation & Expansion] Minimum concentration (Cmin) of CS2009 [Time frame: Up to approximately 2 years]
• [Dose Escalation & Expansion] Number of participants with anti-CS2009 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 Expansion] Number of participants with adverse events (AEs) [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.
• 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.

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.

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

China · 23 centers

• Beijing Cancer Hospital — Beijing
• Jilin Cancer Hospital — Changchun
• Hunan Cancer Hospital — Changsha
• Sichuan Cancer Hospital — Chengdu
• West China Hospital of Sichuan University — Chengdu
• Fujian Cancer Hospital — Fuzhou
• Sun Yat-sen Memorial Hospital, Sun Yat-sen University — Guangzhou
• Sun Yat-Sen University Cancer Center — Guangzhou
• … and 15 more centers

Australia · 8 centers

• Alfred Hospital (Alfred Health) — Melbourne
• Austin Hospital (Austin Health) — Melbourne
• Monash Medical Centre (Monash Health) — Melbourne
• Peter Maccallum Cancer Centre Research — Melbourne
• Icon Cancer Centre South Brisbane — South Brisbane
• Blacktown Hospital — Sydney
• Macquarie University Hospital — Sydney
• Scientia Clinical Research Ltd — Sydney

United States · 2 centers

• START Los Angeles, LLC — Los Angeles
• NEXT Dallas — Irving

Identifiers

NCT: NCT06741644 · CS2009-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗