A Study of HMBD-002, a Monoclonal Antibody Targeting VISTA, as Monotherapy and Combined With Pembrolizumab, in Patients With Advanced Solid Tumors

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

48 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-02-28

Study Completion Date

2024-12-03

Brief Summary

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This is a phase 1/2, open-label, multi-center, first-in-human, two-stage (Part 1: dose escalation and Part 2: dose expansion) study evaluating multiple doses and schedules of intravenously (IV) administered HMBD-002, with or without pembrolizumab KEYTRUDA®, in patients with advanced solid tumors (i.e., locally advanced and unresectable, or metastatic).

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Detailed Description

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This is a phase 1/2, open-label, multi-center study whose principal phase 1 stage objective is to determine the recommended phase 2 dose (RP2D) of the anti-VISTA monoclonal antibody (mAb) as a single agent and combined with the anti-PD-1 mAb pembrolizumab KEYTRUDA® in subjects with advanced solid malignancies.

In the phase 2 stage, the antitumor activity of HMBD-002 alone or combined with pembrolizumab KEYTRUDA® will be evaluated in patients with triple negative breast cancer (TNBC), non-small cell lung cancer (NSCLC) and a wide range of other malignancies known or documented to express VISTA.

Conditions

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Cancer Tumor, Solid Nonsmall Cell Lung Cancer Triple Negative Breast Cancer Malignant Neoplasm Metastatic Cancer Advanced Solid Tumor

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Part 1 - Dose Escalation Phase (Monotherapy)

HMBD-002 administered as a 60-minute IV infusion as a monotherapy. HMBD-002 will be administered on Days 1, 8, and 15 of a 21-day cycle.

Group Type EXPERIMENTAL

HMBD-002

Intervention Type DRUG

IgG4 monoclonal antibody (mAb) targeting the V-domain immunoglobulin suppressor of T cell activation (VISTA) receptor.

Part 1 - Dose Escalation Phase (Combination Therapy)

HMBD-002 administered as a 60-minute IV infusion at escalating doses in combination with pembrolizumab KEYTRUDA®. HMBD-002 will be administered on Days 1, 8, and 15 of a 21-day cycle.

The treatment pembrolizumab KEYTRUDA® will be administered as a 30-minute IV infusion at a dose of 200 mg on Day 1 of every 21-day cycle.

Group Type EXPERIMENTAL

HMBD-002

Intervention Type DRUG

IgG4 monoclonal antibody (mAb) targeting the V-domain immunoglobulin suppressor of T cell activation (VISTA) receptor.

Pembrolizumab

Intervention Type DRUG

IgG4 mAb with high specificity of binding to the PD-1 receptor, thus inhibiting its interaction with PD-L1 and programmed cell death ligand 2 (PD-L2).

Part 2 - Dose Expansion (Monotherapy)

HMBD-002 administered at the MTD/RP2D as a 60-minute IV infusion as a monotherapy in patients with TNBC or NSCLC.

Group Type EXPERIMENTAL

HMBD-002

Intervention Type DRUG

IgG4 monoclonal antibody (mAb) targeting the V-domain immunoglobulin suppressor of T cell activation (VISTA) receptor.

Part 2 - Dose Expansion (Combination Therapy)

HMBD-002 administered at the MTD/RP2D as a 60-minute IV infusion in combination with pembrolizumab KEYTRUDA® at the standard labeled dose in patients with TNBC or NSCLC.

Group Type EXPERIMENTAL

HMBD-002

Intervention Type DRUG

IgG4 monoclonal antibody (mAb) targeting the V-domain immunoglobulin suppressor of T cell activation (VISTA) receptor.

Pembrolizumab

Intervention Type DRUG

IgG4 mAb with high specificity of binding to the PD-1 receptor, thus inhibiting its interaction with PD-L1 and programmed cell death ligand 2 (PD-L2).

Interventions

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HMBD-002

IgG4 monoclonal antibody (mAb) targeting the V-domain immunoglobulin suppressor of T cell activation (VISTA) receptor.

Intervention Type DRUG

Pembrolizumab

IgG4 mAb with high specificity of binding to the PD-1 receptor, thus inhibiting its interaction with PD-L1 and programmed cell death ligand 2 (PD-L2).

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Histologic or cytologic evidence of a malignant solid cancer (any histology) with advanced or metastatic disease and no available therapies known to confer clinical benefit.
2. Tumor tissue, or paraffin block, ideally from the patient's most recent biopsy. A fresh tumor biopsy will be obtained if archival samples are not available.
3. Measurable by Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.
4. At least 18 years old.
5. An Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.
6. Adequate hematopoietic, kidney, and liver functions.
7. A left ventricular ejection fraction (LVEF) ≥ 45%.
8. Women of childbearing potential (WOCBP) must not be pregnant or breastfeeding. A WOCBP must agree to follow contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment.
9. Male subjects must agree to follow contraceptive guidance during the study period and for at least 120 days after the last dose of study treatment.
10. Patient must give informed written consent for the study.

Triple Negative Breast Cancer (TNBC)

1. Histologic or cytologic evidence of TNBC that is advanced or metastatic.
2. Will be requested to undergo a tumor biopsy before treatment and after 6 weeks of treatment.
3. Must have received appropriate treatment with at least one prior regimen for TNBC and there are no available therapies known to confer clinical benefit.

Non-Small Cell Lung Cancer (Monotherapy and Combination)

1. Histologic or cytologic evidence of NSCLC that is advanced or metastatic.
2. Will be requested to undergo a tumor biopsy before treatment and after 6 weeks of treatment.
3. Absence of an activating mutation of the EGFR or ALK.
4. Must have received treatment with an approved therapy if there are other genomic aberrations for which targeted therapies are approved and available.
5. Must have had disease progression on at least one approved or comparable standard therapy for NSCLC.
6. Must have received appropriate prior treatment with a mAb to PD-1 or PD-L1.

Multiple Other Cancers (Combination Therapy Baskets)

1. Histologic or cytologic evidence of an advanced or metastatic cancer aside from TNBC and NSCLC with no available therapies known to confer clinical benefit.
2. Will be requested to undergo a tumor biopsy before treatment and after 6 weeks of treatment.
3. Must have had appropriate treatment for their specific cancer and there is an absence of available therapy with a reasonable likelihood of conferring clinical benefit.

Exclusion Criteria

1. If the patient received prior therapy with an anti-PD-1 or anti-PD-L1 mAb or with an agent targeting stimulatory or co-inhibitory T-cell receptor and was discontinued from that treatment due to a Grade 3 or higher immune related adverse event.
2. Received radiotherapy within 2 weeks of treatment.
3. Received radiotherapy exceeding 30 Gray (Gy) to the lung within 6 months of the first dose of study medication.
4. Received an allogeneic tissue/solid organ transplant.
5. Received a live or live-attenuated vaccine within 30 days prior to the first dose of study medication.
6. Received a VISTA targeting agent.
7. The patient must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline.
8. The patient has an active autoimmune disease that required systemic treatment in the past.
9. Presence of an uncontrolled endocrine disorder.
10. Presence of clinically significant cardiovascular disease.
11. History of (non-infectious) pneumonitis or interstitial pulmonary disease that required steroids or has current pneumonitis or interstitial pulmonary disease.
12. Presence of uncontrolled, clinically significant pulmonary disease.
13. A previous a severe hypersensitivity reaction (≥ Grade 3) to pembrolizumab and/or any of its excipients.
14. A diagnosis of immunodeficiency or is receiving chronic systemic corticosteroids at a dose that exceeds 10 mg daily of prednisone equivalent or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug. Inhaled or topical steroids are permitted in the absence of active autoimmune disease.
15. An uncontrolled intercurrent illness that would limit compliance with the study.
16. A positive status for human immunodeficiency virus (HIV).
17. A known history of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C viral (defined as HCV RNA detected) infection.
18. Oxygen-dependence.
19. A medical condition which, in the opinion of the Investigator, places the patient at an unacceptably high risk for toxicity.
20. A positive COVID test within one week of study treatment if not fully vaccinated.
21. Another active malignancy that is progressing or has required active treatment within the past 3 years.
22. Known active central nervous system metastases and/or carcinomatous meningitis.

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No