Study of TJ033721 (Givastomig) in Subjects With Advanced or Metastatic Solid Tumors

I-Mab Biopharma

Status and phase

Enrolling

Phase 1

Conditions

Metastatic Cancer

Advanced Cancer

Solid Tumor

PDAC - Pancreatic Ductal Adenocarcinoma

Gastric Cancer

Biliary Tract Cancer (BTC)

Esophageal Adenocarcinoma

Gastroesophageal Junction Carcinoma

Treatments

Drug: TJ033721 (givastomig), durvalumab, chemotherapy

Drug: TJ033721 (givastomig)

Drug: TJ033721 (givastomig) , nivolumab, chemotherapy

Drug: TJ033721 (givastomig), chemotherapy

Study type

Interventional

Funder types

Industry

Identifiers

NCT04900818

TJ033721STM101

Details and patient eligibility

About

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.

Enrollment

330 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Sequential Assignment

Masking

Double Blind

330 participants in 4 patient groups

TJ033721 (givastomig)

Experimental group

Description:

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.

Treatment:

Drug: TJ033721 (givastomig)

TJ033721 (givastomig) in combination with nivolumab and chemotherapy

Experimental group

Description:

TJ033721 will be administered in combination with nivolumab and chemotherapy

Treatment:

Drug: TJ033721 (givastomig) , nivolumab, chemotherapy

TJ033721 (givastomig) in combination chemotherapy

Experimental group

Description:

TJ033721 (givastomig) will be administered in combination chemotherapy