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

Inhibrx Biosciences, Inc

Status and phase: Enrolling; Phase 1

Conditions: Colorectal Adenocarcinoma; Ewing Sarcoma

Treatments: Drug: Leucovorin; Drug: Fluorouracil; Drug: carboplatin; Drug: INBRX-109; Drug: pemetrexed; Drug: Irinotecan; Drug: Trifluridine + Tipiracil; Drug: Temozolomide; Drug: Bevacizumab

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: 411 estimated patients

Sex: All

Ages: 12 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Males or females aged ≥12 to less than 85 years for Ewing sarcoma and 18 to less than 85 years of age for other tumors.

2. Part 3 combination therapy expansion tumor types:

   • Histologically confirmed Ewing sarcoma with a classical fusion: Patients with locally advanced or metastatic, unresectable, relapsed, or refractory disease who have received at least 1 but no more than 2 prior lines of systemic treatment with a preferred first line chemotherapy regimens.
   • Colorectal adenocarcinoma: Patients who have failed 1 (one) prior line of systemic therapy that did not include irinotecan.
   • Colorectal adenocarcinoma: Patients who have failed 2 but no more than 3 prior lines of systemic therapy and are FTD/TPI-naïve.

3. Measurable disease as defined by RECISTv1.1 (or modified RECIST for mesothelioma) criteria.

4. Adequate hematologic, coagulation, hepatic and renal function as defined per protocol.

5. Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1, or Karnofsky Performance Status score of ≥60, or Lansky Play-Performance Scale for Children score ≥60 (for patients less than 16 years).

6. Estimated life expectancy of at least 12 weeks.

7. Availability of archival tissue or fresh cancer biopsy are mandatory.

Exclusion criteria

1. Prior treatment with or exposure to DR5 agonists.

2. 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.

3. Allergy or sensitivity to INBRX-109 or known allergies to CHO-produced antibodies.

4. 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.

5. Subject has undergone allogeneic hematopoietic stem cell or bone marrow transplantation within the last 5 years. Exceptions per protocol.

6. Prior or concurrent malignancies. Exceptions per protocol.

7. Hematologic malignancies.

8. Symptomatic active primary CNS tumors, leptomeningeal disease, and CNS metastases. Exceptions per protocol. Patients with any evidence or history of multiple sclerosis (MS) or other demyelinating disorders are excluded.

9. Chronic liver diseases including fatty liver. Exception: Patients < 45 years old with fatty liver disease may be accepted as long as adequate hepatic function as defined in the inclusion/exclusion criteria is confirmed.

10. Acute viral or toxic liver disease within 12 months prior to the first dose of study drug.

11. Evidence or history of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.

12. Known sensitivity or contraindications to the following drugs:

    • Ewing sarcoma: irinotecan or TMZ
    • colorectal adenocarcinoma: FU, leucovorin, irinotecan, bevacizumab or FTP/TPI

13. Clinically significant cardiac condition, including myocardial infarction, uncontrolled angina, cerebrovascular accident, or other acute uncontrolled heart disease less than 3 months prior to enrollment.

14. Acute, hemodynamically significant deep vein thrombosis or clinically significant pulmonary embolism not resolved or stable for at least 3 months prior to the start of study treatment.

15. Major surgery within 4 weeks prior to enrollment on this trial.

16. Systemic infection requiring antibiotics within 2 weeks prior to the first dose of study drug.

17. Other exclusion criteria per protocol.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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411 participants in 14 patient groups

Dose Escalation (Complete)

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 (Complete)

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 (Complete)

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 (Complete)

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 (Complete)

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 (Complete)

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: pemetrexed

Drug: INBRX-109

Drug: carboplatin

Combination Expansion Pancreatic Adenocarcinoma (Complete)

Experimental group

Description:

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

Treatment:

Drug: Irinotecan

Drug: INBRX-109

Drug: Fluorouracil

Drug: Leucovorin

Combination Expansion Adult Ewing Sarcoma

Experimental group

Description:

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

Treatment:

Drug: Temozolomide

Drug: Irinotecan

Drug: INBRX-109

Combination Expansion Colorectal Adenocarcinoma (Complete)

Experimental group

Description:

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

Treatment:

Drug: Irinotecan

Drug: INBRX-109

Drug: Fluorouracil

Drug: Leucovorin

Expansion Solid Tumors (Complete)

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 (Complete)

Experimental group

Description:

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

Treatment:

Drug: Temozolomide

Drug: INBRX-109

Combination Expansion Colorectal Adenocarcinoma patients with FOLFIRI plus bevacizumab

Experimental group

Description:

Colorectal adenocarcinoma will be treated with INBRX-109 with FOLFIRI (FU, leucovorin, and irinotecan) plus bevacizumab

Treatment:

Drug: Bevacizumab

Drug: Irinotecan

Drug: INBRX-109

Drug: Fluorouracil

Drug: Leucovorin

Combination Expansion Colorectal Adenocarcinoma with FTD/TPI plus bevacizumab

Experimental group

Description:

Colorectal adenocarcinoma will be treated with INBRX-109 with FTD/TPI plus bevacizumab

Treatment:

Drug: Bevacizumab

Drug: Trifluridine + Tipiracil

Drug: INBRX-109

Combination Expansion Adolescent Ewing Sarcoma

Experimental group

Description:

Adolescent (12 to \<18) subjects with Ewing Sarcoma will be treated with INBRX-109 in combination with irinotecan and temozolomide

Treatment:

Drug: Temozolomide

Drug: Irinotecan

Drug: INBRX-109