Study of TJ033721 (givastomig) in Subjects with Advanced or Metastatic Solid Tumors
- Conditions
- Solid TumorAdvanced CancerMetastatic CancerEsophageal AdenocarcinomaGastric CancerGastroesophageal Junction Carcinoma
- Interventions
- Drug: TJ033721 (givastomig)Drug: TJ033721 (givastomig) , nivolumab, chemotherapy
- Registration Number
- NCT04900818
- Lead Sponsor
- I-Mab Biopharma US Limited
- Brief Summary
This is an open label, multi-center, multiple dose Phase 1 study to evaluate the safety, tolerability, MTD PK, and PD of TJ033721 (givastomig) in subjects with advanced or metastatic solid tumors.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 168
Part 1 - Monotherapy
• Subjects with advanced or metastatic solid tumor in subjects whose disease has progressed despite standard therapy, or who has no further standard therapy, or who is unsuitable for available standard treatment options.
Part 2 - Combination Therapy Subjects with treatment naïve locally advanced, unresectable or metastatic gastric, GEJ, esophageal adenocarcinoma;
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 with adequate organ function
- Have known PD-L1 status with prior testing by immunohistochemistry and a corresponding combined positive score (CPS)
For dose expansion and Part 2 Combination subjects:
• Must have CLDN18.2-positive tumor expression
Exclusion Criteria
- Prior exposure to CLDN18.2 -targeted therapy
- Prior exposure to 4-1BB agonists
- Second malignancy within the last 3 years with the exception of cutaneous squamous cell carcinoma or cutaneous basal cell carcinoma or cervical carcinoma in situ
- Known active or chronic Hepatitis B or Hepatitis C, other hepatitides
- Unstable/active ulcer or digestive tract bleeding within 6 weeks
- Active autoimmune disease requiring systemic treatment within the past 2 years
- Active interstitial lung disease (ILD) or pneumonitis or a history of ILD or pneumonitis requiring treatment
- Known active CNS metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment;
- New York Heart Association (NYHA) Class 3 or 4 congestive heart failure, severe/unstable angina, myocardial infarction (MI), symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack (TIA), arterial embolism, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery bypass grafting (CABG) in the previous 6 months
- Diagnosis of immunodeficiency such as known active HIV
- Any active infection requiring parenteral treatment
For Part 2 Combination subjects:
• Prior treatment with anti-PD-1 or PD-L1
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description TJ033721 (givastomig) TJ033721 (givastomig) Dose Escalation: TJ033721 will be administered at up to 8 dose levels (0.1, 0.3, 1, 3, 5, 8, 12 and 15 mg/kg) bi weekly (Q2W) and 1 dose level (18 mg/kg) every 3 weeks (Q3W) During dose expansion, TJ033721 will be administered Q2W, starting at the RP2D or MTD in dose escalation. TJ033721 (givastomig) in combination with nivolumab and chemotherapy TJ033721 (givastomig) , nivolumab, chemotherapy TJ033721 will be administered in combination with nivolumab and chemotherapy
- Primary Outcome Measures
Name Time Method Maximum tolerated or administered dose (MTD, MAD) 28 Days Based on DLT definitions
Incidence and severity of AEs Up to 100 days post last dose The CTCAE criteria will be used to assess adverse events on this trial.
Dose-limiting toxicities (DLTs) 28 days
- Secondary Outcome Measures
Name Time Method Pharmacokinetic (PK) Parameters: Cmax up to 100 days post last dose Maximum observed concentration
Pharmacokinetic Parameters: T1/2 up to 100 days post last dose Investigational Product (IP) half-life (T1/2)
Pharmacokinetic (PK) Parameters: AUC∞ Up to 100 days post last dose Area under the curve from time zero extrapolated to infinity (AUC∞)
Pharmacokinetic (PK) Parameters: AUCt up to 100 days post last dose AUC from time zero to the time of the last quantifiable concentration (AUC0-t)
Pharmacokinetic Parameters: Tmax up to 100 days post last dose Time of peak concentration (Tmax)
Trial Locations
- Locations (21)
Stern Center for Cancer Clinical Trials and Research
🇺🇸Orange, California, United States
UCHealth Cancer Care - Anschutz Medical Campus
🇺🇸Aurora, Colorado, United States
Horizon Oncology Research, LLC.
🇺🇸Layfayette, Indiana, United States
Mass General Hospital
🇺🇸Boston, Massachusetts, United States
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
NYU Langone
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Carolina BioOncology Institute
🇺🇸Huntersville, North Carolina, United States
Vanderbilt-Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Mary Crowley Cancer Research
🇺🇸Dallas, Texas, United States
UW Carbone Cancer Center
🇺🇸Madison, Wisconsin, United States
The Second Hospital of Anhui Medical University
🇨🇳Hefei, Anhui, China
Beijing Cancer Hospital
🇨🇳Beijing, Beijing, China
Sixth Affiliated Hospital, Sun Yat-sen University
🇨🇳Guangzhou, Guangdong, China
HARBIN Medical University Cancer Hospital
🇨🇳Harbin,, Heilongjiang, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Hubei Cancer Hospital
🇨🇳Wuhan, Hubei, China
The First Hospital of China Medical University
🇨🇳Shenyang, Liaoning, China
Zhongshan Hospital, Fudan University
🇨🇳Shanghai, Shanghai, China
Tianjin Medical University Cancer Institute and Hospital
🇨🇳Tianjin, Tianjin, China
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
🇨🇳Hongzhou, Zhejiang, China