A Phase 1/2 Clinical Trial to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of HMBD-501 in Patients With HER3-Expressing Solid Tumors

NCT06956690 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: HMBD-501-101
• Study Type: interventional
• Target: 180
• Locations: 2 countries
• Sites: 7

Brief Summary

This study is a Phase 1/2, first-in-human, open-label, clinical trial to assess the safety, tolerability, pharmacokinetics and preliminary efficacy of HMBD-501 in patients with advanced-stage, relapsed and/or refractory human epidermal growth factor receptor 3 (HER3)-expressing solid tumors. The study consists of 2 phases: a dose escalation phase (Phase 1) and a dose expansion phase (Phase 2). The primary objectives of Phase 1 are to characterize the overall safety and tolerability profile of increasing doses of HMBD-501 in patients with advanced-stage solid tumors and identify the recommended Phase 2 dose (RP2D) of ENV-501. During Phase 1, successive cohorts of patients will receive escalating doses of HMBD-501. The results of the dose escalation will determine the RP2D and dosing schedule of HMBD-501 to be administered in the Phase 2 part of the study. The primary objective of Phase 2 is to evaluate the preliminary clinical efficacy of HMBD-501 in dose expansion cohorts.

Conditions

Melanoma (Skin); Non Small Cell Lung Cancer; Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Phase 1 (Dose Escalation): Frequency of treatment-emergent adverse events

  through study completion, an average of 6 months

• Phase 2 (Dose Expansion): Objective Response Rate (ORR)

  Objective Response is defined as Complete Response (CR) or Partial Response (PR) by investigator assessment, measured by revised Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1).

  through study completion, an average of 6 months

Secondary Outcomes (24)

• Phase 1 (Dose Escalation): Disease Control Rate (DCR)

  through study completion, an average of 6 months

• Phase 1 (Dose Escalation): Objective Response Rate (ORR)

  through study completion, an average of 6 months

• Phase 1 (Dose Escalation): maximum blood concentration (Cmax) after a single dose

  At the end of Cycle 1 (each cycle is 21 days)

• Phase 1 (Dose Escalation): time of maximum blood concentration (Tmax) after a single dose

  At the end of Cycle 1 (each cycle is 21 days)

• Phase 1 (Dose Escalation): absorption to time t (AUC0-t) after a single dose

  At the end of Cycle 1 (each cycle is 21 days)

Study Arms (1)

HMBD-501

EXPERIMENTAL

HMBD-501 intravenous injection once every 3 weeks; successive cohorts will receive escalating doses of HMBD-501 until the RP2D is reached

Biological: ENV-501

Interventions

ENV-501 BIOLOGICAL

ENV-501 is a HER3-targeted antibody-drug conjugate (ADC) with a humanized monoclonal antibody (mAb) conjugated with a chemotherapeutic payload via a linker.

HMBD-501

Eligibility Criteria

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

You may qualify if:

• Body weight ≥ 40 kg.
• Willing and able to provide signed written informed consent before any study-related screening procedures are performed.
• Patients with histologically or cytologically confirmed diagnosis of advanced-stage or metastatic HER3+ solid tumors that are relapsed or refractory to or ineligible for standard therapy, or for whom no standard therapy is available; or the patient has documented their refusal of standard of care therapies. These include the following:
• Unresectable or metastatic cutaneous melanoma (HER3+)
• Locally advanced or metastatic mutated EGFR (mEGFR) NSCLC (HER3+)
• Unresectable, locally advanced or metastatic breast cancer
• Relapsed or refractory solid tumors, with documented HER3+ expression such as Pancreatic Ductal Adenocarcinoma (PDAC) and gastric cancers, may be allowed in the protocol following sponsor approval on a case-by -case basis.
• If molecular pathology report to confirm HER3+ status is not available, willingness to undergo fresh tumor biopsy for retrospective assessment of HER3+ status following enrollment..
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2.
• Contraceptive requirements:
• Women of childbearing potential (WOCBP) must use contraception from at least 28 days prior to study start, during the study, and for at least 6 months after the last dose of study drug.
• Males who are sexually active with partner(s) who are WOCBP must agree to use a male condom with spermicide beginning at study start, during the study and for at least 6 months after the last dose of study drug.
• Females must:
• Agree to not donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for at least 6 months after the last dose of study drug.
• Agree to not breastfeed and do not plan to become pregnant during the study and for at least 6 months after the last dose of study drug.

You may not qualify if:

• Any of the following treatment interventions within the specified time frame prior to study drug administration at study start:
• Any anti-tumor-directed drug therapy within 21 days or 5 times the elimination half-life (whichever is shorter).
• Treatment with investigational drugs within 21 days.
• Major surgery within 21 days.
• Radiation therapy ≤4 weeks or radiotherapy that included \>30% of the bone marrow.
• Autologous or allogeneic stem cell transplantation or allogeneic tissue/organ transplant within 3 months.
• CYP3A4 strong inhibitor (including any prescription or non-prescription drugs or herbal supplements) ≤4 half-lives.
• CYP3A4 strong inducer ≤4 half-lives.
• OATP1B inhibitor (including any prescription or non-prescription drugs or herbal supplements) ≤4 half-lives.
• Prior treatment with a HER3-targeted ADC or any exatecan- or exatecan-derivative-conjugated ADC inhibitor as last line of therapy.
• Prior treatment with a topoisomerase I inhibitor as last line of therapy.
• Primary immune deficiency (e.g. congenital syndromes).
• Active and uncontrolled infections requiring intravenous antibiotic or antiviral treatment within 2 weeks prior to study start.
• Known/suspected hypersensitivity against ENV-501, human or humanized immunoglobulin Gs (IgGs), or their ingredients.
• History of noninfectious or drug-induced pneumonitis or interstitial lung disease (ILD).

Sponsors & Collaborators

• Hummingbird Bioscience: lead

Study Sites (7)

Research Site

La Jolla, California, 92093, United States

RECRUITING

Research Site

Indianapolis, Indiana, 46250, United States

RECRUITING

Research Site

Farmington Hills, Michigan, 48334, United States

RECRUITING

Research Site

Dallas, Texas, 75230, United States

RECRUITING

Research Site

San Antonio, Texas, 78229, United States

RECRUITING

Research Site

Campbelltown, New South Wales, 2560, Australia

WITHDRAWN

Research Site

Miranda, New South Wales, 2228, Australia

WITHDRAWN

MeSH Terms

Conditions

Melanoma; Carcinoma, Non-Small-Cell Lung; Breast Neoplasms

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Breast Diseases

Study Officials

• Kevin Heller

  Hummingbird Bioscience

  STUDY DIRECTOR

Central Study Contacts

Kevin Heller, Dr

CONTACT

+65 6978 9377; HMBD Patients <patients@hummingbirdbio.com>

Hummingbird Bioscience Team

CONTACT

HMBD Patients <patients@hummingbirdbio.com>

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2025
• First Posted: May 4, 2025
• Study Start: December 17, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: March 2, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (5); AU (2)