Gastrointestinal Cancer, Head and Neck Cancer, Non Small Cell Lung Cancer, Ovarian Cancer, Ovarian Carcinoma, Triple Negative Breast Cancer
Conditions
Brief summary
This is a multicenter, open label, Phase 2 study of TJ004309 in combination with atezolizumab in patients with advanced or metastatic solid tumors.
Detailed description
This is a multicenter, open label, Phase 2 study of TJ004309 in combination with atezolizumab in patients with advanced or metastatic solid tumors. This clinical study includes two cohorts: Cohort 1 will include Immuno-Oncology (IO) treatment naïve ovarian cancer (OC) patients who have progressed on or after platinum therapy; and Cohort 2 will include patients with head and neck squamous cell carcinoma (HNSCC), non-small cell lung cancer (NSCLC), gastrointestinal cancer (GC), triple negative breast cancer (TNBC), or ovarian carcinoma (OC) with PD-L1 expression ≥ 1%. Additional cohorts for selected tumor types might be added later.
Interventions
DRUGTJ004309
Antibody to CD73
Sponsors
I-Mab Biopharma US Limited
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Cohort 1: Patients with histologically confirmed epithelial ovarian cancer, fallopian tube, or primary peritoneal cancer subjects with any high-grade serous component, progressed on or after platinum-containing therapy and not eligible for further platinum containing treatment (platinum-resistant, platinum-refractory disease defined by progression of disease on a platinum-containing regimen or recurrence of disease within 180 days of receiving the last dose of platinum-based treatment). * Cohort 2: Patients with selected tumor types that have relapsed or progressed after 2 lines of therapy or who are ineligible for other standard of care (SOC) therapies: 1. Histologically or cytologically confirmed metastatic NSCLC 2. Histologically or cytologically confirmed recurrent or metastatic HNSCC (oral cavity, oropharynx, hypopharynx, or larynx) 3. Histologically or cytologically confirmed metastatic or non-resectable advanced metastatic gastric or gastroesophageal adenocarcinoma 4. Histologically or cytologically confirmed unresectable, locally advanced or metastatic TNBC (confirmed HER2-negative, estrogen receptor-negative and progesterone receptor-negative) 5. Histologically confirmed ovarian cancer of all high-grade epithelial types who are IO treatment naïve and have progressed after 3 months on or after platinum-containing therapy 6. PD-L1 expression Tumor Proportion Score (TPS) ≥ 1% for NSCLC and Combined Proportion Score (CPS) ≥ 1% for all other tumor types 7. A 28-day washout period after the completion of programmed death-1 (PD-1)/PD-L1 therapy 8. Patients should have no more than 5 prior lines of therapies * Cohort 2 - (Optional for the ovarian cohort) Pre-treatment fresh tumor biopsies and paired treatment fresh tumor biopsies will be collected from at least 5 patients. Biopsy must be excisional, incisional, or core.
Exclusion criteria
* Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 \[CTLA-4\], OX 40 \[Tumor necrosis factor receptor superfamily, member 4 (TNFRSF4)\], CD137 \[tumor necrosis factor receptor superfamily member 9 (TNFRSF9)\]) (only applies to ovarian cancer patients in Cohorts 1 and 2) * Disease progression within 3 months of starting anti-PD-1 and anti-PD-L1 inhibitors * Known active or chronic Hepatitis B or Hepatitis C, other hepatitides (non-alcohol steatohepatitis, alcohol or drug-related, autoimmune) serology at screening or cirrhosis * Active autoimmune disease requiring systemic treatment within the past 12 months * Active interstitial lung disease (ILD) or pneumonitis or a history of ILD * Brain involvement with cancer, spinal cord compression, carcinomatous meningitis, or new evidence of brain or leptomeningeal disease; unless the lesion(s) have been radiated or resected, are considered fully treated and inactive, are asymptomatic, and no steroids have been administered for CNS disease over the 7 days prior to study treatment * Angina, myocardial infarction (MI), symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack TIA), arterial embolism, pulmonary embolism, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery bypass grafting (CABG) within 6 months prior to study treatment * Known human immunodeficiency virus (HIV) unless CD4+ T cell count \> 350 cells/μL with an undetectable viral load
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Assess the Efficacy of TJ004309 Combined With Atezolizumab in a Cohort of Patients With Platinum-resistant IO Naive Ovarian Carcinoma and a Separate Biomarker Enriched Cohort of Subjects With Selected Tumor Types | Up to 66 weeks | Anti-tumor activity of the combination of TJ004309 and atezolizumab was measured by objective response rate (ORR) based on RECIST 1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| o Assess the Efficacy of TJ004309 Combined With Atezolizumab in a Cohort of Patients With Platinum-resistant IO Naive Ovarian Carcinoma and a Separate Biomarker Enriched Cohort of Subjects With Selected Tumor Types | Up to 66 weeks | Anti-tumor activity of the combination of TJ004309 and atezolizumab was measured by objective response rate (ORR) based on iRECIST. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Platinum resistant or refractory IO naive ovarian carcinoma (OC)
TJ004309 20mg/kg Q3W and atezolizumab 1200 mg/flat dose Q3W | 17 |
| Cohort 2 HNSCC, NSCLC, GC, TNBC, OC
TJ004309 20 mg/kg Q3W and atezolizumab 1200 mg/flat dose Q3W | 8 |
| Total | 25 |
Baseline characteristics
| Characteristic | Cohort 1 | Cohort 2 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 2 Participants | 11 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 6 Participants | 14 Participants |
| Age, Continuous | 64.7 years STANDARD_DEVIATION 10.84 | 60.0 years STANDARD_DEVIATION 11.35 | 63.2 years STANDARD_DEVIATION 11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 6 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) White | 13 Participants | 6 Participants | 19 Participants |
| Region of Enrollment United States | 17 participants | 8 participants | 25 participants |
| Sex: Female, Male Female | 17 Participants | 3 Participants | 20 Participants |
| Sex: Female, Male Male | 0 Participants | 5 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 17 | 2 / 8 |
| other Total, other adverse events | 0 / 17 | 0 / 8 |
| serious Total, serious adverse events | 7 / 17 | 4 / 8 |
Outcome results
Primary
To Assess the Efficacy of TJ004309 Combined With Atezolizumab in a Cohort of Patients With Platinum-resistant IO Naive Ovarian Carcinoma and a Separate Biomarker Enriched Cohort of Subjects With Selected Tumor Types
Anti-tumor activity of the combination of TJ004309 and atezolizumab was measured by objective response rate (ORR) based on RECIST 1.1
Time frame: Up to 66 weeks
Population: Efficacy evaluable analysis set was defined as all patients who received at least one dose of study drug and undergo at least one post-baseline tumor assessment. Patients who died before the first scheduled post-baseline tumor assessment were also included in the efficacy evaluable analysis set- only 23 of the 25 subjects were efficacy evaluable per this definition.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 | To Assess the Efficacy of TJ004309 Combined With Atezolizumab in a Cohort of Patients With Platinum-resistant IO Naive Ovarian Carcinoma and a Separate Biomarker Enriched Cohort of Subjects With Selected Tumor Types | 1 Participants |
| Cohort 2 | To Assess the Efficacy of TJ004309 Combined With Atezolizumab in a Cohort of Patients With Platinum-resistant IO Naive Ovarian Carcinoma and a Separate Biomarker Enriched Cohort of Subjects With Selected Tumor Types | 0 Participants |
Secondary
o Assess the Efficacy of TJ004309 Combined With Atezolizumab in a Cohort of Patients With Platinum-resistant IO Naive Ovarian Carcinoma and a Separate Biomarker Enriched Cohort of Subjects With Selected Tumor Types
Anti-tumor activity of the combination of TJ004309 and atezolizumab was measured by objective response rate (ORR) based on iRECIST.
Time frame: Up to 66 weeks
Population: Overall number of participants is the number of subjects who had at least one response assessment (iRECIST) from N=6 out 15 in Cohort 1 and N=4 out of 8 in Cohort 2
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 | o Assess the Efficacy of TJ004309 Combined With Atezolizumab in a Cohort of Patients With Platinum-resistant IO Naive Ovarian Carcinoma and a Separate Biomarker Enriched Cohort of Subjects With Selected Tumor Types | 0 Participants |
| Cohort 2 | o Assess the Efficacy of TJ004309 Combined With Atezolizumab in a Cohort of Patients With Platinum-resistant IO Naive Ovarian Carcinoma and a Separate Biomarker Enriched Cohort of Subjects With Selected Tumor Types | 0 Participants |