Study of an Anti-HER3 Antibody, HMBD-001, With or Without Chemotherapy in Patients With NRG1 Gene Fusion Advanced Solid Tumors

Sponsor

Hummingbird Bioscience (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05919537

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a phase 1b multi-center, open-label study of HMBD-001 with or without chemotherapy in participants with advanced solid tumors harboring NRG1 gene fusions.

Condition or Disease	Intervention/Treatment	Phase
Non-Small Cell Lung Cancer Pancreatic Cancer Locally Advanced Solid Tumor Metastatic Solid Tumor	Drug: HMBD-001 Drug: Docetaxel Drug: Nab-paclitaxel Drug: Gemcitabine	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

54 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1b Study to Evaluate HMBD-001 With or Without Chemotherapy in Participants With Advanced Solid Tumors Harboring NRG1 Gene Fusions

Anticipated Study Start Date :

Jun 30, 2023

Anticipated Primary Completion Date :

Mar 1, 2031

Anticipated Study Completion Date :

Mar 1, 2031

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A Participants with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) harboring NRG1 gene fusions	Drug: HMBD-001 HMBD-001 is a humanized IgG1 anti-HER3 monoclonal antibody (mAb). It is administered IV weekly Drug: Nab-paclitaxel Nab-paclitaxel 125 mg/m^2 IV on days 1, 8, 15, every 4 weeks Drug: Gemcitabine Gemcitabine 1000 mg/m^2 IV on days 1, 8, 15, every 4 weeks
Experimental: Arm B Participants with non-small cell lung cancer (NSCLC) harboring NRG1 gene fusions	Drug: HMBD-001 HMBD-001 is a humanized IgG1 anti-HER3 monoclonal antibody (mAb). It is administered IV weekly Drug: Docetaxel Docetaxel 75 mg/m^2 IV once every 3 weeks
Experimental: Arm C Participants with other solid tumors harboring NRG1 gene fusions	Drug: HMBD-001 HMBD-001 is a humanized IgG1 anti-HER3 monoclonal antibody (mAb). It is administered IV weekly

Arm

Intervention/Treatment

Experimental: Arm A

Participants with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) harboring NRG1 gene fusions

Drug: HMBD-001

HMBD-001 is a humanized IgG1 anti-HER3 monoclonal antibody (mAb). It is administered IV weekly

Drug: Nab-paclitaxel

Nab-paclitaxel 125 mg/m^2 IV on days 1, 8, 15, every 4 weeks

Drug: Gemcitabine

Gemcitabine 1000 mg/m^2 IV on days 1, 8, 15, every 4 weeks

Experimental: Arm B

Participants with non-small cell lung cancer (NSCLC) harboring NRG1 gene fusions

Drug: HMBD-001

HMBD-001 is a humanized IgG1 anti-HER3 monoclonal antibody (mAb). It is administered IV weekly

Drug: Docetaxel

Docetaxel 75 mg/m^2 IV once every 3 weeks

Experimental: Arm C

Participants with other solid tumors harboring NRG1 gene fusions

Drug: HMBD-001

HMBD-001 is a humanized IgG1 anti-HER3 monoclonal antibody (mAb). It is administered IV weekly

Outcome Measures

Primary Outcome Measures

Incidence and Nature of Adverse Events (AEs) [From the time the ICF is signed until 30 days after last dose of study treatment]
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered to be related to the study treatment.
Arm A and B only: Incidence and nature of dose-limiting toxicities (DLTs) during the first cycle of treatment [Arm A: During the first four weeks of study treatment Arm B: During the first three weeks of study treatment]
DLTs will be assessed during the safety run-in phase and are defined as toxicities that meet pre-defined severity criteria and assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, intercurrent illness, or concomitant medications that occurs within the first cycle (4 weeks for Arm A, 3 weeks for Arm B) of treatment
Objective Response Rate (ORR) by RECIST V1.1 [Up to 24 months]
The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR, based on RECIST Version 1.1

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Ability to understand and be willing to sign an informed consent form
Males and females aged over 18 years
Eastern Cooperative Oncology Group (ECOG) status of 0 to 1
Histologic or cytologic evidence of an advanced malignant solid that is resistant/refractory to standard systemic therapy, or for which there is no standard systemic therapy or reasonable therapy in the physician's judgment likely to result in clinical benefit, or the participant has demonstrated to be intolerable to such therapy, or if such therapy has been refused by the participant
Cancer harboring an NRG1 gene fusion with EGF-like domain; Arm A: Participants with locally advanced or metastatic pancreatic adenocarcinoma that have not received prior treatment with gemcitabine or nab-paclitaxel and /or have not received more than 2 lines of systemic therapy for advanced disease; Arm B: Participants with locally advanced or metastatic non-small cell lung cancer that have not received prior treatment with docetaxel and /or have not received more than 2 lines of systemic therapy for advanced disease; Arm C: Participants must not be eligible to participate in Arm A or B
Have an estimated life expectancy of at least 3 months
Have an archival tumour sample available or have a site of disease amenable to biopsy and be willing to undergo a biopsy prior to the receipt of the assigned study treatment
Have adequate organ function
Females must be non-pregnant and non-lactating, willing to use a highly effective method of contraception from screening until study completion or be either surgically sterile or post-menopausal
Males must be surgically sterile, abstinent, or if engaged in sexual relations with a woman of child-bearing potential, the participant and his partner must be surgically sterile or using an acceptable, highly effective contraceptive method from screening until study completion

Exclusion Criteria:

Prior treatment with HMBD-001, pertuzumab, or an agent that specifically targets HER3, including pan-HER tyrosine kinase inhibitors
Persistent clinically significant toxicities (Grade ≥2) from previous anti-cancer therapy except for Grade >2 toxicities that are considered unlikely to put the participant at an increased risk of treatment-related toxicity and/or impact the study results e.g., alopecia
Most recent anti-cancer therapy including radiotherapy at least 4 weeks, or nitrosourea or mitomycin 3 at least 6 weeks, or 5 half-lives whichever is shorter prior to starting the assigned study treatment
Symptomatic primary Central Nervous System (CNS) cancer or metastases unless the symptoms are stable for at least 28 days prior to the first dose of the study drug and any symptoms have returned to baseline
Evidence of abnormal cardiac function
History of uncontrolled allergic reactions and/or known expected hypersensitivity to the study drugs used in the treatment arm to which the participant is to be enrolled into
Any other known active malignancy except for treated cervical intraepithelial neoplasia, or non-melanoma skin cancer
Any uncontrolled illness or significant uncontrolled condition(s) requiring systemic treatment
Known Human Immunodeficiency Virus (HIV) infection
Active hepatitis B or hepatitis C infection
Pregnant or breast feeding
COVID 19 infection within 3 months prior to the first dose of the study drug
COVID 19 vaccination within 14 days prior to the first dose of the study drug