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A Study of HMBD-002, a Monoclonal Antibody Targeting VISTA, as Monotherapy and Combined With Pembrolizumab

Primary Purpose

Cancer, Tumor, Solid, Nonsmall Cell Lung Cancer

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
HMBD-002
Pembrolizumab
Sponsored by
Hummingbird Bioscience
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • The City of Hope National Medical CenterRecruiting
  • Cedars-Sinai Medical CenterRecruiting
  • Stanford Cancer InstituteRecruiting
  • Smilow Cancer Hospital - Yale New Heaven HealthRecruiting
  • UTSW Medical CenterRecruiting
  • The University of Texas MD Anderson Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Part 1 - Dose Escalation Phase (Monotherapy)

Part 1 - Dose Escalation Phase (Combination Therapy)

Part 2 - Dose Expansion (Monotherapy)

Part 2 - Dose Expansion (Combination Therapy)

Arm Description

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.

HMBD-002 administered as a 60-minute IV infusion at escalating doses in combination with pembrolizumab. HMBD-002 will be administered on Days 1, 8, and 15 of a 21-day cycle. Pembrolizumab will be administered as a 30-minute IV infusion at a dose of 200 mg on Day 1 of every 21-day cycle.

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

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

Outcomes

Primary Outcome Measures

Dose-limiting Toxicity
The incidence of DLTs during the DLT assessment period.
Dose-Finding
Determination of the MTD or maximum tested dose, and the RP2D.
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.

Secondary Outcome Measures

Pharmacokinetics of HMBD-002
Maximum Plasma Concentration (Cmax)
Pharmacokinetics of HMBD-002
Area Under the Curve (AUC)
Objective Response Rate (ORR)
ORR according to RECIST v1.1.
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.
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.
Overall Survival (OS)
Time from the date of initiation of study therapy to the date of death from any cause.

Full Information

First Posted
September 21, 2021
Last Updated
August 7, 2023
Sponsor
Hummingbird Bioscience
Collaborators
Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT05082610
Brief Title
A Study of HMBD-002, a Monoclonal Antibody Targeting VISTA, as Monotherapy and Combined With Pembrolizumab
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 1, 2022 (Actual)
Primary Completion Date
October 2024 (Anticipated)
Study Completion Date
January 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hummingbird Bioscience
Collaborators
Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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, in patients with advanced solid tumors (i.e., locally advanced and unresectable, or metastatic).
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 in subjects with advanced solid malignancies. In the phase 2 stage, the antitumor activity of HMBD-002 alone or combined with pembrolizumab 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cancer, Tumor, Solid, Nonsmall Cell Lung Cancer, Triple Negative Breast Cancer, Malignant Neoplasm, Metastatic Cancer, Advanced Solid Tumor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
240 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Part 1 - Dose Escalation Phase (Monotherapy)
Arm Type
Experimental
Arm Description
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.
Arm Title
Part 1 - Dose Escalation Phase (Combination Therapy)
Arm Type
Experimental
Arm Description
HMBD-002 administered as a 60-minute IV infusion at escalating doses in combination with pembrolizumab. HMBD-002 will be administered on Days 1, 8, and 15 of a 21-day cycle. Pembrolizumab will be administered as a 30-minute IV infusion at a dose of 200 mg on Day 1 of every 21-day cycle.
Arm Title
Part 2 - Dose Expansion (Monotherapy)
Arm Type
Experimental
Arm Description
HMBD-002 administered at the MTD/RP2D as a 60-minute IV infusion as a monotherapy in patients with TNBC or NSCLC.
Arm Title
Part 2 - Dose Expansion (Combination Therapy)
Arm Type
Experimental
Arm Description
HMBD-002 administered at the MTD/RP2D as a 60-minute IV infusion in combination with pembrolizumab at the standard labeled dose in patients with TNBC or NSCLC.
Intervention Type
Drug
Intervention Name(s)
HMBD-002
Intervention Description
IgG4 monoclonal antibody (mAb) targeting the V-domain immunoglobulin suppressor of T cell activation (VISTA) receptor.
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Intervention Description
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).
Primary Outcome Measure Information:
Title
Dose-limiting Toxicity
Description
The incidence of DLTs during the DLT assessment period.
Time Frame
First 21 days of treatment.
Title
Dose-Finding
Description
Determination of the MTD or maximum tested dose, and the RP2D.
Time Frame
Screening to 90 days from last dose.
Title
Frequency and Severity of Adverse Events (AE)
Description
The incidences and percentages of patients experiencing AEs summarized by NCI CTCAE version 5.0 grade and by causality.
Time Frame
Screening to 90 days from last dose.
Secondary Outcome Measure Information:
Title
Pharmacokinetics of HMBD-002
Description
Maximum Plasma Concentration (Cmax)
Time Frame
Day 1 of dosing through 21 days post last dose.
Title
Pharmacokinetics of HMBD-002
Description
Area Under the Curve (AUC)
Time Frame
Day 1 of dosing through 21 days post last dose.
Title
Objective Response Rate (ORR)
Description
ORR according to RECIST v1.1.
Time Frame
Day 1 of dosing through every 90 after the last dose.
Title
Duration of Response (DoR)
Description
Time from the date measurement criteria are first met for PR or CR to the date measurement criteria are first met for PD.
Time Frame
Day 1 of dosing through every 90 after the last dose.
Title
Progression Free Survival (PFS)
Description
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.
Time Frame
Day 1 of dosing through every 90 after the last dose.
Title
Overall Survival (OS)
Description
Time from the date of initiation of study therapy to the date of death from any cause.
Time Frame
Day 1 of dosing through every 90 after the last dose.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria (Phase 1 and 2 Stages) 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. Inclusion Criteria for HMBD-002 Phase 2 Stage 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) Histologic or cytologic evidence of NSCLC that is advanced or metastatic. Will be requested to undergo a tumor biopsy before treatment and after 6 weeks of treatment. Absence of an activating mutation of the EGFR or ALK. Must have received treatment with an approved therapy if there are other genomic aberrations for which targeted therapies are approved and available. Must have had disease progression on at least one approved or comparable standard therapy for NSCLC. Must have received appropriate prior treatment with a mAb to PD-1 or PD-L1. Multiple Other Cancers (Combination Therapy Baskets) Histologic or cytologic evidence of an advanced or metastatic cancer aside from TNBC and NSCLC with no available therapies known to confer clinical benefit. Will be requested to undergo a tumor biopsy before treatment and after 6 weeks of treatment. 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 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. A positive status for human immunodeficiency virus (HIV). A known history of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C viral (defined as HCV RNA detected) infection. Oxygen-dependence. A medical condition which, in the opinion of the Investigator, places the patient at an unacceptably high risk for toxicity. A positive COVID test within one week of study treatment if not fully vaccinated. Another active malignancy that is progressing or has required active treatment within the past 3 years. Known active central nervous system metastases and/or carcinomatous meningitis.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kon Yew Kwek, BMBCh, DPhil
Phone
+65 6979 5574
Email
k.y.kwek@hummingbirdbio.com
Facility Information:
Facility Name
The City of Hope National Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Miguel A Villalona-Calero, MD
Facility Name
Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Monica Mita, MD
Phone
310-248-6729
Email
monica.mita@cshs.org
Facility Name
Stanford Cancer Institute
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anastasia L Harper
Phone
650-727-0378
Email
anastasia.harper@stanford.edu
First Name & Middle Initial & Last Name & Degree
Melinda Telli, MD
Facility Name
Smilow Cancer Hospital - Yale New Heaven Health
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06511
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ingrid Palma
First Name & Middle Initial & Last Name & Degree
Joseph W Kim, MD
Facility Name
UTSW Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joshua Gruber, MD
First Name & Middle Initial & Last Name & Degree
Joshua Gruber, MD
Facility Name
The University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jordi Rodon, MD, PhD
Phone
713-792-5603
Email
jrodon@mdanderson.org
First Name & Middle Initial & Last Name & Degree
Uyen Vu
Phone
713-794-1254
Email
umvu@mdanderson.org

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

A Study of HMBD-002, a Monoclonal Antibody Targeting VISTA, as Monotherapy and Combined With Pembrolizumab

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