Advanced Cancer, Biliary Tract Cancer (BTC), Esophageal Adenocarcinoma, Gastric Cancer, Gastroesophageal Junction Carcinoma, Metastatic Cancer, PDAC - Pancreatic Ductal Adenocarcinoma, Solid Tumor
Conditions
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.
Interventions
DRUGTJ033721 (givastomig)
Tetravalent IgG(H)-scFv fusion-type of bi-specific antibody (BsAb)
DRUGTJ033721 (givastomig) , nivolumab, chemotherapy
Tetravalent IgG(H)-scFv fusion-type of bi-specific antibody (BsAb), nivolumab, chemotherapy
DRUGTJ033721 (givastomig), chemotherapy
Tetravalent IgG(H)-scFv fusion-type of bi-specific antibody (BsAb), chemotherapy
DRUGTJ033721 (givastomig), durvalumab, chemotherapy
Tetravalent IgG(H)-scFv fusion-type of bi-specific antibody (BsAb), durvalumab, chemotherapy
Sponsors
I-Mab Biopharma US Limited
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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; Part 3: Combination Therapy Subjects with unresectable, locally advanced or metastatic histologically confirmed pancreatic adenocarcinoma; Part 4: Combination Therapy Subjects with unresectable, locally advanced or metastatic histologically confirmed biliary tract cancer. * 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, Part 3, Part 4 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, 3, 4 Combination subjects: • Prior treatment with anti-PD-1 or PD-L1 agent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-limiting toxicities (DLTs) | 28 days | — |
| 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. |
| Maximum tolerated or administered dose (MTD, MAD) | 28 Days | Based on DLT definitions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 (PK) Parameters: Cmax | up to 100 days post last dose | Maximum observed concentration |
| Pharmacokinetic Parameters: Tmax | up to 100 days post last dose | Time of peak concentration (Tmax) |
| Pharmacokinetic Parameters: T1/2 | up to 100 days post last dose | Investigational Product (IP) half-life (T1/2) |
Countries
China, United States
Contacts
CONTACTClinical Development
Outcome results
None listed