Trial Title:
Study of ORM-5029 in Subjects With HER2-Expressing Advanced Solid Tumors
NCT ID:
NCT05511844
Condition:
HER2-positive Breast Cancer
HER-2 Protein Overexpression
HER-2 Gene Amplification
HER2 Gene Mutation
Conditions: Keywords:
HER2 Expressing
HER2 Positive
HER2 Associated
Antibody Drug Conjugate
Protein-Degradation
GSPT1
Celmod
Imid
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
ORM-5029
Description:
Intravenous infusion
Arm group label:
Part 1 Dose Escalation
Arm group label:
Part 2 Dose Expansion
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.
Criteria for eligibility:
Criteria:
KEY INCLUSION CRITERIA
- 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:
1. Have a negative pregnancy test (serum) at Screening.
2. 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:
1. Agree to use at least one highly effective form of contraception during study
treatment and after the last dose of ORM-5029.
2. 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.
- Life expectancy of ≥12 weeks according to the Investigator's judgment.
KEY EXCLUSION CRITERIA
- 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.
1. 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
- No prior history of AIDS-defining opportunistic infections
- Received established anti-retroviral therapy for at least four weeks and
have an HIV viral load <400 copies/mL prior to enrolment.
2. Participants who are hepatitis B surface antigen positive are eligible if they
have received HBV antiviral therapy for at least 4 weeks prior to the first
dose of ORM-5029 and have undetectable HBV viral load prior to enrolment. Note:
Participants must remain on antiviral therapy throughout study intervention and
follow local guidelines for HBV antiviral therapy post completion of study
intervention.
3. Participants with a history of HCV infection are eligible if they have received
curative treatment and HCV viral load is undetectable prior to enrolment.
Participants who are HCV Ab positive but HCV RNA negative due to prior
treatment or natural resolution are eligible. Note: Participants must have
completed curative antiviral therapy at least 4 weeks prior to enrolment.
- Acute or chronic uncontrolled renal disease, pancreatitis, or liver disease (with
exception of participants with Gilbert's Syndrome, asymptomatic gallstones, liver
metastases, or stable chronic liver disease per Investigator assessment).
- Moderate or severe hepatic impairment (i.e., Child-Pugh class B or C).
- Any bleeding disorder (e.g., coagulopathy) or history of chronic bleeding and
participants on therapeutic anticoagulant therapy during the treatment. Note:
Participants on prophylactic anticoagulant therapy are considered eligible.
- Life-threatening illness, medical condition, active uncontrolled infection, or organ
system dysfunction.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of Alabama Birmingham
Address:
City:
Birmingham
Zip:
35233
Country:
United States
Status:
Recruiting
Contact:
Phone:
205-801-8415
Investigator:
Last name:
Nusrat Jahan, MD
Email:
Principal Investigator
Facility:
Name:
University of California - Los Angeles
Address:
City:
Los Angeles
Zip:
90095
Country:
United States
Status:
Recruiting
Contact:
Phone:
310-998-4747
Investigator:
Last name:
Nicolaos J Palaskas, MD, PhD
Email:
Principal Investigator
Facility:
Name:
Dana Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Contact:
Phone:
617-632-3800
Investigator:
Last name:
Antonio Giordano, MD, PhD
Email:
Principal Investigator
Facility:
Name:
Washington University
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Status:
Recruiting
Contact:
Phone:
314-867-3627
Investigator:
Last name:
Katherine Clifton, MD
Email:
Principal Investigator
Facility:
Name:
Memorial Sloan Kettering Cancer Center
Address:
City:
New York
Zip:
10065
Country:
United States
Status:
Recruiting
Contact:
Phone:
332-275-4665
Investigator:
Last name:
Joshua Drago, MD
Email:
Principal Investigator
Facility:
Name:
Weill Cornell Medicine-New York
Address:
City:
New York
Zip:
10065
Country:
United States
Status:
Recruiting
Contact:
Phone:
646-962-2800
Investigator:
Last name:
Massimo Cristofanilli, MD
Email:
Principal Investigator
Facility:
Name:
Sarah Cannon Research Institute at Tennessee Oncology
Address:
City:
Nashville
Zip:
32703
Country:
United States
Status:
Recruiting
Contact:
Phone:
615-320-5090
Investigator:
Last name:
Erika P Hamilton, MD
Email:
Principal Investigator
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Phone:
855-839-7183
Investigator:
Last name:
Paula Pohlmann, MD, PhD
Email:
Principal Investigator
Facility:
Name:
NEXT Oncology
Address:
City:
San Antonio
Zip:
78229
Country:
United States
Status:
Recruiting
Contact:
Phone:
210-580-9500
Investigator:
Last name:
Sharon T Wilks, MD, FACP
Email:
Principal Investigator
Facility:
Name:
NEXT Oncology - Virginia Cancer Specialists
Address:
City:
Fairfax
Zip:
22031
Country:
United States
Status:
Recruiting
Contact:
Phone:
703-280-5390
Investigator:
Last name:
Alex Spira, MD, PhD
Email:
Principal Investigator
Facility:
Name:
Fred Hutchinson Cancer Center
Address:
City:
Seattle
Zip:
98109
Country:
United States
Status:
Recruiting
Contact:
Phone:
855-557-0555
Investigator:
Last name:
William R. Gwin III, MD
Email:
Principal Investigator
Start date:
October 3, 2022
Completion date:
October 2025
Lead sponsor:
Agency:
Orum Therapeutics USA, Inc.
Agency class:
Industry
Source:
Orum Therapeutics USA, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05511844
