PDL1x41BB: Study of INBRX-105 in Patients With Solid Tumors

Sponsor

Inhibrx, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03809624

Collaborator

(none)

170

Enrollment

Locations

Arms

Anticipated Duration (Months)

14.2

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a first-in-human, open-label, nonrandomized, four-part Phase 1 trial to determine the safety profile and identify the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of INBRX-105 and INBRX-105 in combination with Pembrolizumab. INBRX-105, a next generation bispecific antibody, targets the human programmed death-ligand 1 (PD-L1) receptor and the human 4-1BB receptor. INBRX-105 provides localized conditional T-cell co-stimulation through 4-1BB agonism.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Solid Tumors Non-small Cell Lung Cancer Melanoma Head and Neck Squamous Cell Carcinoma Gastric Adenocarcinoma Renal Cell Carcinoma Urothelial Carcinoma Esophageal Adenocarcinoma	Drug: INBRX-105 - PDL1x41BB antibody Drug: Pembrolizumab	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

170 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open-Label, Multicenter, First-in-Human, Dose-Escalation, Phase 1 Study of INBRX-105 and INBRX-105 in Combination With Pembrolizumab in Patients With Locally Advanced or Metastatic Solid Tumors

Actual Study Start Date :

Jan 30, 2019

Anticipated Primary Completion Date :

Aug 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single Agent Escalation INBRX-105 will be escalated in patients with locally advanced or metastatic solid tumors.	Drug: INBRX-105 - PDL1x41BB antibody The active ingredient of INBRX-105 is a recombinant, humanized, bispecific IgG antibody that targets the human programmed death-ligand 1 (PD-L1) receptor and the human 4-1BB receptor.
Experimental: Expansion Cohort Non-small Cell Lung Cancer Patients will be treated with single-agent INBRX-105 at either the MTD or RP2D.	Drug: INBRX-105 - PDL1x41BB antibody The active ingredient of INBRX-105 is a recombinant, humanized, bispecific IgG antibody that targets the human programmed death-ligand 1 (PD-L1) receptor and the human 4-1BB receptor.
Experimental: Expansion Cohort Melanoma Patients will be treated with single-agent INBRX-105 at either the MTD or RP2D.	Drug: INBRX-105 - PDL1x41BB antibody The active ingredient of INBRX-105 is a recombinant, humanized, bispecific IgG antibody that targets the human programmed death-ligand 1 (PD-L1) receptor and the human 4-1BB receptor.
Experimental: Expansion Cohort PD-L1 Positive Basket Patients with gastric or gastro-esophageal junction adenocarcinoma, renal cell carcinoma, and urothelial (transitional) cell carcinoma will be treated with single-agent INBRX-105 at either the MTD or RP2D.	Drug: INBRX-105 - PDL1x41BB antibody The active ingredient of INBRX-105 is a recombinant, humanized, bispecific IgG antibody that targets the human programmed death-ligand 1 (PD-L1) receptor and the human 4-1BB receptor.
Experimental: Expansion Cohort Head and Neck Squamous Cell Carcinoma Patients with head and neck squamous cell carcinoma will be treated with single-agent INBRX-105 at either the MTD or RP2D.	Drug: INBRX-105 - PDL1x41BB antibody The active ingredient of INBRX-105 is a recombinant, humanized, bispecific IgG antibody that targets the human programmed death-ligand 1 (PD-L1) receptor and the human 4-1BB receptor.
Experimental: INBRX-105 Escalation in Combination with Pembrolizumab INBRX-105 will be escalated in combination with Pembrolizumab in pateitns with locally advanced or metastatic solid tumors.	Drug: INBRX-105 - PDL1x41BB antibody The active ingredient of INBRX-105 is a recombinant, humanized, bispecific IgG antibody that targets the human programmed death-ligand 1 (PD-L1) receptor and the human 4-1BB receptor. Drug: Pembrolizumab Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle. Other Names: Keytruda
Experimental: Combination Expansion Cohort Non-small Cell Lung Cancer Patients will be treated with INBRX-105 in combination with Pembrolizumab.	Drug: INBRX-105 - PDL1x41BB antibody The active ingredient of INBRX-105 is a recombinant, humanized, bispecific IgG antibody that targets the human programmed death-ligand 1 (PD-L1) receptor and the human 4-1BB receptor. Drug: Pembrolizumab Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle. Other Names: Keytruda
Experimental: Combination Expansion Cohort Melanoma Patients will be treated with INBRX-105 in combination with Pembrolizumab.	Drug: INBRX-105 - PDL1x41BB antibody The active ingredient of INBRX-105 is a recombinant, humanized, bispecific IgG antibody that targets the human programmed death-ligand 1 (PD-L1) receptor and the human 4-1BB receptor. Drug: Pembrolizumab Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle. Other Names: Keytruda
Experimental: Combination Expansion Cohort Cohort PD-L1 Positive Basket Patients with head and neck squamous cell carcinoma, gastro-esophageal junction adenocarcinoma, renal cell carcinoma, and urothelial (transitional) cell carcinoma will be treated with INBRX-105 in combination with Pembrolizumab.	Drug: INBRX-105 - PDL1x41BB antibody The active ingredient of INBRX-105 is a recombinant, humanized, bispecific IgG antibody that targets the human programmed death-ligand 1 (PD-L1) receptor and the human 4-1BB receptor. Drug: Pembrolizumab Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle. Other Names: Keytruda
Experimental: Combination Expansion Cohort Treatment Naive Non-small Cell Lung Cancer Treatment naive patients (PD-L1 IHC between 1 and 49%) will be treated with INBRX-105 in combination with Pembrolizumab.	Drug: INBRX-105 - PDL1x41BB antibody The active ingredient of INBRX-105 is a recombinant, humanized, bispecific IgG antibody that targets the human programmed death-ligand 1 (PD-L1) receptor and the human 4-1BB receptor. Drug: Pembrolizumab Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle. Other Names: Keytruda

Outcome Measures

Primary Outcome Measures

Frequency of adverse events of INBRX-105 [Up to 2-3 years]
Adverse events will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.
Severity of adverse events of INBRX-105 [Up to 2-3 years]
Severity of adverse events will be assessed and assigned by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.
Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of INBRX-105 [Up to 2-3 years]
The MTD and/or RP2D of INBRX-105 will be determined.

Secondary Outcome Measures

Area under the serum concentration time curve (AUC) of INBRX-105 [Up to 2-3 years]
Area under the serum concentration time curve (AUC) of INBRX-105 will be determined.
Maximum observed serum concentration (Cmax) of INBRX-105 [Up to 2-3 years]
Maximum observed serum concentration (Cmax) of INBRX-105 will be determined.
Trough observed serum concentration (Ctrough) of INBRX-105 [Up to 2-3 years]
Trough observed serum concentration (Cmax) of INBRX-105 will be determined.
Time to Cmax (Tmax) of INBRX-105 [Up to 2-3 years]
Time to Cmax (Tmax) of INBRX-105 will be determined.
Immunogenicity of INBRX-105 [Up to 2-3 years]
Frequency of anti-drug antibodies (ADA) against INBRX-105 will be determined.

Other Outcome Measures

Anti-tumor activity of INBRX-105 [Up to 2-3 years]
Tumor response will be determined by the revised Response Evaluation Criteria in Solid Tumors version 1.1 (RECISTv1.1).
Anti-tumor activity of INBRX-105 [Up to 2-3 years]
Tumor response will be determined by immune Response Evaluation Criteria in Solid Tumors (iRECIST).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Parts 1 and 3 (escalation cohorts): Patients with locally advanced or metastatic non-resectable solid tumors, whose disease has progressed despite standard therapy and for whom no further standard therapy exists.
Parts 2 and 4 (expansion cohorts): Patients with non-small cell lung cancer, melanoma, head and neck squamous cell carcinoma, gastric or gastro-esophageal junction adenocarcinoma, renal cell carcinoma, or urothelial (transitional) cell carcinoma, with locally advanced or metastatic, non-resectable disease, which has progressed despite standard therapy or for whom no standard or clinically acceptable therapy exists.
Part 4 treatment naive NSCLC cohort: Locally advanced or metastatic, non-resectable NSCLC, who have not received prior systemic treatment, including CPI, for advanced or metastatic disease. PD-L1 IHC Tumor Proportion Score (TPS) ≥ 1% and </= 49%. In Part 4, all patients with non-squamous NSCLC must have documentation of absence of tumor activating EGFR mutations and absence of ALK gene rearrangements.
Refractory or relapsed to anti-PD-1 or anti-PD-L1, and anti-CTLA4 if applicable (NOTE: For all tumor types with checkpoint inhibitor approvals) with exception of the treatment naive NSCLC cohort.
PD-L1 positivity by immunohistochemistry (IHC): Parts 1 and 3 (escalation cohorts) PD-L1 positivity is not required. Parts 2 and 4 (expansion cohorts): Combined Positive Score (CPS) or Tumor Proportion Score (TPS) above certain thresholds as defined per protocol.
Adequate hematologic, coagulation, hepatic and renal function as defined per protocol.
Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.

Exclusion Criteria:

Prior exposure to 4-1BB agonists.
Receipt of any investigational product or any approved anticancer drug(s) or biological product(s) within 4 weeks prior to the first dose of study drug.

Exceptions: Hormone replacement therapy, testosterone, or oral contraceptives. NOTE:

Previous exposure to anti-PD-L1 checkpoint inhibitor requires a minimum washout period of 24 weeks prior to the first dose of study drug.

Hematologic malignancies (e.g., ALL, AML, MDS, CLL, CML, NHL, Hodgkin lymphoma and multiple myeloma).
Prior or concurrent malignancies. Exception: Subjects with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessments of INBRX-105.
Known or active primary central nervous system (CNS) tumors, leptomeningeal disease and CNS metastases. Exception: Subjects with previously treated, asymptomatic, and clinically stable CNS metastases may be allowed study entry if certain criteria apply.
Grade ≥ 3 immune-related adverse events (irAEs) or irAE that lead to discontinuation of prior immunotherapy. Some exceptions as defined per protocol apply.
Active autoimmune disease or documented history of autoimmune disease that required systemic steroids or other immunosuppressive medications. Certain exceptions as defined in protocol apply.
Treatment with systemic immunosuppressive medications within 4 weeks prior to the first dose of study drug. Certain exceptions as defined in protocol apply.
History of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV). Exceptions as defined in protocol for expansion cohorts will apply.
History of hepatitis or cirrhosis (e.g., non-alcohol steatohepatitis, alcohol or drug-related, autoimmune, hepatitis B, or hepatitis C). Exceptions as defined in protocol for expansion cohorts will apply.
Active interstitial lung disease (ILD) or pneumonitis or a history of ILD or pneumonitis requiring treatment with steroids or other immunosuppressive medications.
Clinically significant cardiac condition, including myocardial infarction, uncontrolled angina, cerebrovascular accident, or other acute uncontrolled heart disease < 3 months; left ventricular ejection fraction (LVEF) < 50%; New York Heart Association (NYHA) Class III or IV congestive heart failure; or uncontrolled hypertension.
Active, hemodynamically significant pulmonary embolism within 3 months prior to enrollment on this trial.
Major surgery within 4 weeks prior to enrollment on this trial.
Anti-infectious drug treatments (i.e., antibiotics) within 4 weeks prior to the first dose of study drug.
Prior organ allograft transplantations or allogeneic peripheral blood stem cell (PBSC) or bone marrow (BM) transplantation.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	HonorHealth Research Institute	Scottsdale	Arizona	United States	85258
2	City of Hope	Duarte	California	United States	91010
3	Valkyrie Clinical Trials	Los Angeles	California	United States	90069
4	Emory University - Winship Cancer Institute	Atlanta	Georgia	United States	30322
5	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
6	START Midwest	Grand Rapids	Michigan	United States	49546
7	Nebraska Cancer Specialists	Omaha	Nebraska	United States	68130
8	Abramson Cancer Center - University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
9	MD Anderson Cancer Center	Houston	Texas	United States	77030
10	NEXT Oncology	San Antonio	Texas	United States	78229
11	START Mountain Region	West Valley City	Utah	United States	84119
12	Virginia Cancer Specialists	Fairfax	Virginia	United States	22031