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

A Phase 1 Study of HMBD-002-V4C26 (HMBD-002), a Monoclonal Antibody Targeting VISTA, as Monotherapy and Combined With Pembrolizumab, in Patients With Advanced Solid Malignancies

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).

Study Overview

• Status: Completed
• Conditions: Cancer; Metastatic Cancer; Triple Negative Breast Cancer; Advanced Solid Tumor; Nonsmall Cell Lung Cancer; Malignant Neoplasm; Tumor, Solid
• Intervention / Treatment: Drug: HMBD-002; Drug: Pembrolizumab

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • The City of Hope National Medical Center
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Palo Alto, California, United States, 94304
      • Stanford Cancer Institute
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Smilow Cancer Hospital - Yale New Heaven Health
  • Texas
    • Dallas, Texas, United States, 75390
      • UTSW Medical Center
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria (Phase 1 and 2 Stages)

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.

Inclusion Criteria for HMBD-002 Phase 2 Stage

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: HMBD-002; IgG4 monoclonal antibody (mAb) targeting the V-domain immunoglobulin suppressor of T cell activation (VISTA) receptor.
Experimental: 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.	Drug: HMBD-002; IgG4 monoclonal antibody (mAb) targeting the V-domain immunoglobulin suppressor of T cell activation (VISTA) receptor.
Experimental: 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.	Drug: HMBD-002; IgG4 monoclonal antibody (mAb) targeting the V-domain immunoglobulin suppressor of T cell activation (VISTA) receptor.; 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).
Experimental: 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.	Drug: HMBD-002; IgG4 monoclonal antibody (mAb) targeting the V-domain immunoglobulin suppressor of T cell activation (VISTA) receptor.; 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting Toxicity	The incidence of DLTs during the DLT assessment period.	First 21 days of treatment.
Dose-Finding	Determination of the MTD or maximum tested dose, and the RP2D.	Screening to 90 days from last dose.
Frequency and Severity of Adverse Events (AE)	The incidences and percentages of patients experiencing AEs summarized by NCI CTCAE version 5.0 grade and by causality.	Screening to 90 days from last dose.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR according to RECIST v1.1.	Day 1 of dosing through every 90 after the last dose.
Progression Free Survival (PFS)	Time from the date of initiation of study therapy to the date measurement criteria are first met for PD or death from any cause, whichever occurs first.	Day 1 of dosing through every 90 after the last dose.
Overall Survival (OS)	Time from the date of initiation of study therapy to the date of death from any cause.	Day 1 of dosing through every 90 after the last dose.
Pharmacokinetics of HMBD-002	Maximum Plasma Concentration (Cmax)	Day 1 of dosing through 21 days post last dose.
Pharmacokinetics of HMBD-002	Area Under the Curve (AUC)	Day 1 of dosing through 21 days post last dose.
Duration of Response (DoR)	Time from the date measurement criteria are first met for PR or CR to the date measurement criteria are first met for PD.	Day 1 of dosing through every 90 after the last dose.

Collaborators and Investigators

• Sponsor: Hummingbird Bioscience
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2022
• Primary Completion (Actual): November 5, 2024
• Study Completion (Actual): December 3, 2024

Study Registration Dates

• First Submitted: September 21, 2021
• First Submitted That Met QC Criteria: October 14, 2021
• First Posted (Actual): October 19, 2021

Study Record Updates

• Last Update Posted (Estimated): October 16, 2025
• Last Update Submitted That Met QC Criteria: October 14, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplastic Processes; Lung Neoplasms; Skin Diseases; Breast Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Breast Neoplasms; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Neoplasms; Neoplasm Metastasis; Carcinoma, Non-Small-Cell Lung; Triple Negative Breast Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; pembrolizumab
• Other Study ID Numbers: HMBD-002-V4C26-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No