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

NCT05082610 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: HMBD-002-V4C26-01
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 6

Brief Summary

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).

Conditions

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

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (6)

• Pharmacokinetics of HMBD-002

  Day 1 of dosing through 21 days post last dose.

• Pharmacokinetics of HMBD-002

  Day 1 of dosing through 21 days post last dose.

• Objective Response Rate (ORR)

  Day 1 of dosing through every 90 after the last dose.

• Duration of Response (DoR)

  Day 1 of dosing through every 90 after the last dose.

• Progression Free Survival (PFS)

  Day 1 of dosing through every 90 after the last dose.

Study Arms (4)

Part 1 - Dose Escalation Phase (Monotherapy)

EXPERIMENTAL

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

Part 1 - Dose Escalation Phase (Combination Therapy)

EXPERIMENTAL

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; Drug: Pembrolizumab

Part 2 - Dose Expansion (Monotherapy)

EXPERIMENTAL

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

Part 2 - Dose Expansion (Combination Therapy)

EXPERIMENTAL

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; Drug: Pembrolizumab

Interventions

HMBD-002 DRUG

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

Part 1 - Dose Escalation Phase (Combination Therapy); Part 1 - Dose Escalation Phase (Monotherapy); Part 2 - Dose Expansion (Combination Therapy); Part 2 - Dose Expansion (Monotherapy)

Pembrolizumab 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 1 - Dose Escalation Phase (Combination Therapy); Part 2 - Dose Expansion (Combination Therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• Measurable by Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.
• At least 18 years old.
• An Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.
• Adequate hematopoietic, kidney, and liver functions.
• A left ventricular ejection fraction (LVEF) ≥ 45%.
• 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.
• 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.
• Patient must give informed written consent for the study.
• Triple Negative Breast Cancer (TNBC)
• Histologic or cytologic evidence of TNBC that is advanced or metastatic.
• Will be requested to undergo a tumor biopsy before treatment and after 6 weeks of treatment.
• 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)

You may not qualify if:

• 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.
• Received radiotherapy within 2 weeks of treatment.
• Received radiotherapy exceeding 30 Gray (Gy) to the lung within 6 months of the first dose of study medication.
• Received an allogeneic tissue/solid organ transplant.
• Received a live or live-attenuated vaccine within 30 days prior to the first dose of study medication.
• Received a VISTA targeting agent.
• The patient must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline.
• The patient has an active autoimmune disease that required systemic treatment in the past.
• Presence of an uncontrolled endocrine disorder.
• Presence of clinically significant cardiovascular disease.
• History of (non-infectious) pneumonitis or interstitial pulmonary disease that required steroids or has current pneumonitis or interstitial pulmonary disease.
• Presence of uncontrolled, clinically significant pulmonary disease.
• A previous a severe hypersensitivity reaction (≥ Grade 3) to pembrolizumab and/or any of its excipients.
• 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.
• An uncontrolled intercurrent illness that would limit compliance with the study.

Sponsors & Collaborators

• Hummingbird Bioscience: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (6)

The City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Stanford Cancer Institute

Palo Alto, California, 94304, United States

Location

Smilow Cancer Hospital - Yale New Heaven Health

New Haven, Connecticut, 06511, United States

Location

UTSW Medical Center

Dallas, Texas, 75390, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Neoplasms; Carcinoma, Non-Small-Cell Lung; Triple Negative Breast Neoplasms; Neoplasm Metastasis

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2021
• First Posted: October 19, 2021
• Study Start: February 28, 2022
• Primary Completion: November 5, 2024
• Study Completion: December 3, 2024
• Last Updated: October 16, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)