Study of ORM-5029 in Subjects With HER2-Expressing Advanced Solid Tumors

NCT05511844 | Terminated Phase 1 FDA Drug

• 1 other identifier: ORM-5029-01-001
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 11

Brief Summary

This is a Phase 1 first-in-human study of ORM-5029 in participants with HER2-expressing advanced solid tumors. The study consists of two parts: a Part 1 Dose Escalation and Part 2 Dose Expansion.

Conditions

HER2-positive Breast Cancer; HER-2 Protein Overexpression; HER-2 Gene Amplification; HER2 Gene Mutation

Keywords

HER2 Expressing; HER2 Positive; HER2 Associated; Antibody Drug Conjugate; Protein-Degradation; GSPT1; Celmod; Imid

Outcome Measures

Primary Outcomes (4)

• Determination of Maximum Tolerated Dose (MTD) and Expansion Dose Level (EDL) [Dose Escalation Only]

  Identify the Dose-limiting Toxicities (DLTs) for each dose level tested and determine the MTD and EDL for ORM-5029

  DLT assessment period: At the end of Cycle 1 (each cycle is 21 or 28 days); Approximately 18 months for MTD and EDL

• Incidence of Adverse Events (AEs)

  Evaluate the safety and tolerability of ORM-5029 by identifying the treatment-emergent adverse events (TEAEs)

  Every cycle (each cycle is 21 or 28 days) until study discontinuation; Approximately 30 months

• Define the Objective Response Rate (ORR) of ORM-5029 based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 [Dose Expansion Only]

  ORR is defined as the percentage of subjects with Partial Response (PR) or Complete Response (CR)

  Approximately 30 months

• Define the Duration of Response (DOR) of ORM-5029 based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 [Dose Expansion Only]

  DOR is defined as the length of time from the date of the first documented response (PR or CR) until the date of first documented progression or date of death from any cause, whichever came first

  Approximately 30 months

Secondary Outcomes (10)

• Assess pharmacokinetic (PK) parameters including area under the concentration versus time curve from time 0 hours to the last quantifiable concentration (AUC0-last) and from time 0 hours to infinity (AUC0-inf)

  Serial PK collections at on Days 1, 2, 4, 8 and 15 of Cycle 1 and Day 1 of Cycle 3 (Pre-dose and at multiple timepoints [up to 6 hours]; each cycle is 21 or 28 days)

• Assess maximum plasma and serum drug concentration (Cmax)

  Serial PK collections at on Days 1, 2, 4, 8 and 15 of Cycle 1 and Day 1 of Cycle 3 (Pre-dose and at multiple timepoints [up to 6 hours]; each cycle is 21 or 28 days)

• Define time to Cmax (Tmax)

  Serial PK collections at on Days 1, 2, 4, 8 and 15 of Cycle 1 and Day 1 of Cycle 3 (Pre-dose and at multiple timepoints [up to 6 hours]; each cycle is 21 or 28 days)

• Access pharmacokinetic (PK) parameters including terminal rate consent and terminal elimination half-life (t1/2)

  Serial PK collections at Baseline, Days 2, 4, 8 and 15 of Cycle 1 and Day 1 of Cycle 3 (Pre-dose and at multiple timepoints [up to 6 hours]; each cycle is 21 or 28 days)

• Define Clinical Benefit Rate (CBR) of ORM-5029 based on RECIST 1.1

  Approximately 30 months

Study Arms (2)

Part 1 Dose Escalation

EXPERIMENTAL

All participants receive ORM-5029 in escalating dose cohorts in Part 1 Dose Escalation and at the Expansion Dose Level (EDL) in Part 2 Dose Expansion.

Drug: ORM-5029

Part 2 Dose Expansion

EXPERIMENTAL

All participants receive ORM-5029 at dose levels with pharmacodynamic activity or efficacy signals (Expansion Cohort A) or at the Expansion Dose Level (EDL) (Expansion Cohorts B and C).

Drug: ORM-5029

Interventions

ORM-5029 DRUG

Intravenous infusion

Part 1 Dose Escalation; Part 2 Dose Expansion

Eligibility Criteria

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

You may qualify if:

• Have histologically confirmed advanced breast cancer that is HER2+ by In Situ Hybridization (ISH) and/or at least 1+ staining by Immunohistochemistry (IHC), determined at the institution.
• Participant is not a candidate for or would be unlikely to tolerate or derive significant clinical benefit from, appropriate standard-of-care therapy, or the participant declines standard-of-care therapy, or the participant did not tolerate standard-of-care therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
• Evaluable disease (for participants in the Part 1 Dose Escalation) or measurable disease as per RECIST v1.1 (for participants in the Part 2 Dose Expansion).
• Acceptable organ function at Screening.
• Acceptable hematologic function at Screening.
• Adequate coagulation parameters at Screening.
• Female participants of childbearing potential must:
• Have a negative pregnancy test (serum) at Screening.
• Agree to use at least one highly effective form of contraception during study treatment and after the last dose of ORM-5029.
• Male participants with female partners of childbearing potential must:
• Agree to use at least one highly effective form of contraception during study treatment and after the last dose of ORM-5029.
• Refrain from donating sperm during their participation in the study and after the last dose of ORM-5029.
• Resolution of all toxicities of prior therapy or surgical procedures to baseline or Grade 1 (except for neuropathy, which must have resolved to Grade ≤2, hypothyroidism requiring medication, and alopecia).
• Adequate cardiac left ventricular function, as defined by a left ventricular ejection fraction (LVEF) ≥ institutional standard of normal.

You may not qualify if:

• Systemic antineoplastic agent or radiation therapy given within 14 days prior to the first dose of ORM-5029.
• Known sensitivity to any of the ingredients of ORM-5029, including previously reported infusion reactions to pertuzumab leading to pertuzumab treatment discontinuation.
• History of other malignancy within the last 2 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or other malignancy with a similar expected curative outcome.
• Symptomatic central nervous system (CNS) metastases or presence of leptomeningeal disease. Participant with previously treated brain metastases may participate.
• Pregnant or breastfeeding.
• Major surgery (excluding placement of vascular access) within 4 weeks prior to first dose of ORM-5029.
• Uncontrolled hypertension (systolic BP ≥160 mmHg; diastolic BP ≥100 mmHg) despite adequate treatment prior to the first dose of ORM-5029.
• Cardiac diseases currently or within the last 6 months as defined by New York Heart Association ≥Class 2.
• Mean resting QT interval corrected for heart rate (QTc) interval using the Fridericia formula (QTcF) \>450 msec for males and \>470 msec for females.
• Concurrent treatment with medications that are well-known to prolong the QT interval (see CredibleMeds website: https://www.crediblemeds.org/) unless a participant is QT stable on QT prolonging medication for at least 4 weeks.
• Severe dyspnea at rest, due to complications of advanced malignancy.
• Past medical history or complications of interstitial lung disease. Note: Participants with history of radiation induced interstitial lung disease may be enrolled if the participant's symptoms have recovered
• Active, uncontrolled bacterial, fungal, or viral infection, including known hepatitis B virus (HBV), known hepatitis C virus (HCV), known human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS) related illness.
• HIV Seropositive participants who are healthy and at low risk for AIDS-related outcomes can be considered eligible. HIV positive participants must be evaluated and discussed with the Medical Monitor, and should have:
• CD4+ (cluster of differentiation 4) T-cell counts ≥350 cells/μL

Sponsors & Collaborators

• Orum Therapeutics USA, Inc.: lead

Study Sites (11)

University of Alabama Birmingham

Birmingham, Alabama, 35233, United States

Location

University of California - Los Angeles

Los Angeles, California, 90095, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Weill Cornell Medicine-New York

New York, New York, 10065, United States

Location

Sarah Cannon Research Institute at Tennessee Oncology

Nashville, Tennessee, 32703, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

NEXT Oncology

San Antonio, Texas, 78229, United States

Location

NEXT Oncology - Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

Location

Study Design

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

Study Record Dates

• First Submitted: August 17, 2022
• First Posted: August 23, 2022
• Study Start: October 3, 2022
• Primary Completion: June 2, 2025
• Study Completion: June 2, 2025
• Last Updated: July 4, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)