Study of INBRX-105 and INBRX-105 With Pembrolizumab in Patients With Solid Tumors Including Head and Neck Cancer (PDL1x41BB)

Inhibrx Biosciences, Inc

Status and phase

Active, not recruiting

Phase 1

Conditions

Melanoma

Nasopharyngeal Carcinoma

Non-small Cell Lung Cancer

Esophageal Adenocarcinoma

Oropharyngeal Carcinoma

Renal Cell Carcinoma

Metastatic Solid Tumors

Gastric Adenocarcinoma

Head and Neck Squamous Cell Carcinoma

Treatments

Drug: INBRX-105 - PDL1x41BB antibody

Drug: Pembrolizumab

Study type

Interventional

Funder types

Industry

Identifiers

NCT03809624

Ph 1 Ph 2 INBRX-105

Details and patient eligibility

About

This is a first-in-human, open-label, nonrandomized, four-part 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.

Enrollment

160 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Parts 1 and 3 (escalation cohorts; completed): 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.
Part 2 (expansion cohorts): Patients with non-small cell lung cancer, cutaneous melanoma, head and neck squamous cell carcinoma or solid tumors amenable to paired biopsies, 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 relapsed or refractory to CPI cohorts: NSCLC, cutaneous melanoma, HNSCC, MSI/TMB-high or MMRd solid tumors
Part 4 CPI naive cohorts: locally advanced or metastatic, non-resectable NSCLC or HNSCC
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.

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Sequential Assignment

Masking

None (Open label)

160 participants in 11 patient groups

Single Agent Escalation

Experimental group

Description:

INBRX-105 will be escalated in patients with locally advanced or metastatic solid tumors.

Treatment:

Drug: INBRX-105 - PDL1x41BB antibody

Expansion Cohort Non-small Cell Lung Cancer

Experimental group

Description:

Patients will be treated with single-agent INBRX-105 at either the MTD or RP2D.

Treatment:

Drug: INBRX-105 - PDL1x41BB antibody

Expansion Cohort Melanoma

Experimental group

Description:

Patients will be treated with single-agent INBRX-105 at either the MTD or RP2D.

Treatment:

Drug: INBRX-105 - PDL1x41BB antibody

Expansion Cohort PD-L1 Positive Basket

Experimental group

Description:

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.

Treatment:

Drug: INBRX-105 - PDL1x41BB antibody

Expansion Cohort Nasopharyngeal or Oropharyngeal Carcinoma

Experimental group

Description:

Patients with head and neck squamous cell carcinoma (NPC or OPC) will be treated with single-agent INBRX-105 at either the MTD or RP2D.

Treatment:

Drug: INBRX-105 - PDL1x41BB antibody

INBRX-105 Escalation in Combination with Pembrolizumab

Experimental group

Description:

INBRX-105 will be escalated in combination with Pembrolizumab in pateitns with locally advanced or metastatic solid tumors.

Treatment:

Drug: Pembrolizumab

Drug: INBRX-105 - PDL1x41BB antibody

Combination Expansion Cohort Non-small Cell Lung Cancer

Experimental group

Description:

CPI relapsed/refractory patients will be treated with INBRX-105 in combination with Pembrolizumab.

Treatment:

Drug: Pembrolizumab

Drug: INBRX-105 - PDL1x41BB antibody

Combination Expansion Cohort Melanoma

Experimental group

Description:

CPI relapsed/refractory patients will be treated with INBRX-105 in combination with Pembrolizumab.

Treatment:

Drug: Pembrolizumab

Drug: INBRX-105 - PDL1x41BB antibody

Combination Expansion Cohort Cohort PD-L1 Positive Basket

Experimental group

Description:

CPI-relapsed/refractory 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.

Treatment:

Drug: Pembrolizumab

Drug: INBRX-105 - PDL1x41BB antibody

Combination Expansion Cohort CPI Naive Non-small Cell Lung Cancer

Experimental group

Description:

CPI naive patients (PD-L1 IHC between 1 and 49%) will be treated with INBRX-105 in combination with Pembrolizumab.

Treatment:

Drug: Pembrolizumab

Drug: INBRX-105 - PDL1x41BB antibody

Combination Expansion Cohort CPI Naive HNSCC

Experimental group