Phase 1 Study of INBRX-109 in Subjects With Locally Advanced or Metastatic Solid Tumors Including Sarcomas

Inhibrx

Status and phase: Enrolling; Phase 1

Conditions: Malignant Pleural Mesothelioma; Colorectal Adenocarcinoma; SDH-deficient Solid Tumors; Chondrosarcoma; Sarcoma; Pancreatic Adenocarcinoma; Ewing Sarcoma; Solid Tumors; GIST; Gastric Adenocarcinoma

Treatments: Drug: 5-fluorouracil; Drug: Carboplatin; Drug: Pemetrexed; Drug: Temozolomide; Drug: Irinotecan; Drug: INBRX-109; Drug: Cisplatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT03715933

Ph1 INBRX-109

Details and patient eligibility

About

This is a first-in-human, open-label, non-randomized, three-part phase 1 trial of INBRX-109, which is a recombinant humanized tetravalent antibody targeting the human death receptor 5 (DR5).

Enrollment: 240 estimated patients

Sex: All

Ages: 12 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Males or females aged ≥12 to <85 years for Ewing sarcoma and 18 to <85 years of age for GIST.
• Escalation: Histologically or cytologically-confirmed advanced/metastatic or non-resectable solid tumors, including sarcoma, that are refractory or intolerant to standard therapy, or for which no standard therapy exists that is likely to confer any clinical benefit.
• Expansion Cohorts: Malignant pleural mesothelioma, gastric adenocarcinoma, colorectal adenocarcinoma, pancreatic adenocarcinoma and certain sarcoma subtypes (e.g., chondrosarcoma, Ewing sarcoma), GIST, and SDH-def solid tumors with locally advanced or metastatic, non-resectable disease, that are refractory or intolerant to standard therapy, or for which no standard therapy exists that is likely to confer any clinical benefit.
• Measurable disease as defined by RECISTv1.1 (or modified RECIST for mesothelioma) criteria.
• Adequate hematologic, coagulation, hepatic and renal function as defined per protocol.
• Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 for Part 1 and ECOG PS of 0, 1 or 2 for Parts 2 and 3.

Exclusion criteria

• Prior treatment with or exposure to DR5 agonists.
• Receipt of any anticancer therapy (including investigational agents) within 4 weeks or within 5 half-lives prior to the first dose of study treatment. Exceptions per protocol.
• Receipt of radiotherapy within 4 weeks prior to the first dose of study treatment, and liver-directed within 12 months prior to the first dose of study drug.
• Subject has undergone allogeneic hematopoietic stem cell or bone marrow transplantation within the last 5 years. Exception: Participants who have had a stem cell or bone marrow transplant > 5 years ago are eligible for enrollment, as long as there are no symptoms of graft-versus-host disease (GVHD).
• 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-109.
• Hematologic malignancies.
• Symptomatic active primary CNS tumors, leptomeningeal disease, and CNS metastases. Exceptions per protocol.
• Chronic liver disease including but not limited to cirrhosis, non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH), alcohol-related liver disease, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, multiple liver hemangioma (except incidental finding of clinically nonsignificant liver hemangioma), hepatic or biliary autoimmune disorders (ie, primary biliary cholangitis, autoimmune hepatitis), history of portal or hepatic vein thrombosis, and sinusoidal occlusion syndrome. Exceptions per protocol.
• Acute viral or toxic liver disease within 12 months prior to the first dose of study drug.
• Evidence or history of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.
• Clinically significant cardiac condition, including myocardial infarction, uncontrolled angina, cerebrovascular accident, or other acute uncontrolled heart disease < 3 months;
• Sensitivity or contraindications to INBRX-109, irinotecan, or temozolomide.
• Major surgery within 4 weeks prior to enrollment on this trial.
• Systemic infection requiring antibiotics within 2 weeks prior to the first dose of study drug.
• Pregnant or nursing females.
• Patients who are receiving strong cytochrome P450 (CYP) 3A inhibitors and/or inducers, and/or UGT1A1 inhibitors within 14 days of Cycle 1 Day 1.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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240 participants in 11 patient groups

Dose Escalation

Experimental group

Description:

INBRX-109 will be escalated (3+3 design) in subjects with locally advanced or metastatic solid tumors including sarcomas.

Treatment:

Drug: INBRX-109

Expansion Malignant Pleural Mesothelioma

Experimental group

Description:

Subjects with malignant pleural mesothelioma will be treated with single-agent INBRX-109 at either the MTD or RP2D.

Treatment:

Drug: INBRX-109

Expansion Gastric Adenocarcinoma

Experimental group

Description:

Subjects with gastric adenocarcinoma will be treated with single-agent INBRX-109 at either the MTD or RP2D.

Treatment:

Drug: INBRX-109

Expansion Colorectal Adenocarcinoma

Experimental group

Description:

Subjects with colorectal (CRC) adenocarcinoma will be treated with single-agent INBRX-109 at either the MTD or RP2D.

Treatment:

Drug: INBRX-109

Expansion Sarcomas

Experimental group

Description:

Subjects with certain sarcoma subtypes will be treated with single-agent INBRX-109 at either the MTD or RP2D.

Treatment:

Drug: INBRX-109

Combination Expansion Malignant Pleural Mesothelioma

Experimental group

Description:

Subjects with malignant pleural mesothelioma will be treated with INBRX-109 in combination with chemotherapies (carboplatin, cisplatin, carboplatin and pemetrexed, or cisplatin and pemetrexed)

Treatment:

Drug: INBRX-109

Drug: Cisplatin

Drug: Pemetrexed

Drug: Carboplatin

Combination Expansion Pancreatic Adenocarcinoma

Experimental group

Description:

Subjects with pancreatic adenocarcinoma will be treated with INBRX-109 in combination with 5FU/irinotecan based chemotherapy

Treatment:

Drug: INBRX-109

Drug: Irinotecan

Drug: 5-fluorouracil

Combination Expansion Ewing Sarcoma

Experimental group

Description:

Subjects with Ewing Sarcoma will be treated with INBRX-109 in combination with irinotecan and temozolomide

Treatment:

Drug: INBRX-109

Drug: Irinotecan

Drug: Temozolomide

Combination Expansion Colorectal Adenocarcinoma

Experimental group

Description:

Subjects with colorectal adenocarcinoma will be treated with INBRX-109 in combination with FOLFIRI based chemotherapy

Treatment:

Drug: INBRX-109

Drug: Irinotecan

Drug: 5-fluorouracil

Expansion Solid Tumors

Experimental group

Description:

Subjects with Solid tumors and high BMI will be treated with single-agent INBRX-109 at either the MTD or RP2D.

Treatment:

Drug: INBRX-109

Combination Expansion SDH-deficient solid tumors or GIST

Experimental group

Description:

Subjects with SDH-deficient solid tumors or GIST will be treated with INBRX-109 in combination with temozolomide

Treatment:

Drug: INBRX-109

Drug: Temozolomide