ORM-5029 for HER2-Positive Breast Cancer

No longer recruiting at 11 trial locations

Overseen By Orum Therapeutics USA, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Orum Therapeutics USA, Inc.

Must not be taking: QT prolonging medications

Disqualifiers: CNS metastases, Uncontrolled hypertension, Cardiac diseases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called ORM-5029 for individuals with advanced HER2-positive breast cancer. The goal is to assess the safety and effectiveness of this drug at various doses. It targets those who have not had success with other treatments or cannot take standard treatments. Participants must have advanced breast cancer confirmed as HER2-positive. As a Phase 1 trial, participants will be among the first to receive this treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have taken any systemic cancer treatments or radiation therapy within 14 days before starting the trial, and you should not be on medications that prolong the QT interval unless stable for at least 4 weeks.

Is there any evidence suggesting that ORM-5029 is likely to be safe for humans?

Research has shown that ORM-5029 could be a promising treatment for tumors expressing HER2. In early studies, it effectively targeted cancer cells in lab tests and animal studies, suggesting potential efficacy in humans.

ORM-5029 is now undergoing its first human trials to assess safety. Researchers proceed to this step when lab and animal studies provide sufficient evidence of potential safety for humans. The main goal of this trial phase is to evaluate how well participants tolerate the treatment, with close monitoring for any side effects.

As this is an early trial, complete safety data for humans is not yet available. However, advancing to this trial phase indicates enough evidence supports its potential safety for human testing. Participants will be closely monitored to address any side effects promptly. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for HER2-positive breast cancer, which typically include options like trastuzumab and pertuzumab, ORM-5029 is being developed with a unique mechanism. It targets cancer cells more precisely by honing in on specific HER2 expressions, potentially leading to fewer side effects and greater treatment effectiveness. Researchers are excited about ORM-5029 because it offers hope for improved outcomes by delivering its therapeutic agents directly to the cancer cells, minimizing damage to healthy cells. This targeted approach could mean better efficacy and a more personalized treatment experience for patients.

What evidence suggests that ORM-5029 might be an effective treatment for HER2-positive breast cancer?

Research shows that ORM-5029 could be a promising treatment for HER2-positive breast cancer. Studies have found that targeting HER2 in breast cancer can improve survival rates and help control the disease. ORM-5029 is a new drug that specifically targets and breaks down a protein called GSPT1, found in HER2-positive cancer cells, which is crucial for its potential effectiveness. Early research suggests that ORM-5029 is highly active in models with low HER2 levels, both in lab tests and in living organisms. Although human studies have provided limited information, these early findings offer a strong basis for its potential effectiveness. Participants in this trial will receive ORM-5029 in either the Part 1 Dose Escalation or Part 2 Dose Expansion arms, where researchers are exploring different dosing strategies. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for adults with advanced breast cancer that tests positive for HER2. Participants should have tried standard treatments without success, or be unable to tolerate them. They must have a life expectancy of at least 12 weeks, good heart function, and stable organ and blood functions. Women of childbearing age need a negative pregnancy test and agree to use contraception; men also need to agree to contraception use.

Inclusion Criteria

Adequate coagulation parameters at Screening

My blood test results are within normal ranges.

My side effects from previous treatments have mostly gone away or are mild.

Exclusion Criteria

I have brain metastases but have received treatment for them.

Pregnant or breastfeeding

I haven't had cancer in the last 2 years, except for certain non-aggressive types.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive ORM-5029 in escalating dose cohorts to determine the Maximum Tolerated Dose (MTD) and Expansion Dose Level (EDL)

Approximately 18 months

Dose Expansion

Participants receive ORM-5029 at dose levels with pharmacodynamic activity or efficacy signals

Approximately 30 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ORM-5029

Trial Overview ORM-5029 is being tested in this Phase 1 trial on people with HER2-positive advanced solid tumors. The study has two parts: first, finding the right dose (Dose Escalation), then seeing how well it works at that dose (Dose Expansion).

How Is the Trial Designed?

Group I: Part 2 Dose Expansion Experimental Treatment 1 Intervention

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).

Group II: Part 1 Dose Escalation Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Orum Therapeutics USA, Inc.

Lead Sponsor

Trials

1

Recruited

90+

Published Research Related to This Trial

Trastuzumab (Herceptin) has been shown to significantly improve outcomes in HER-2-positive breast cancer, reducing the risk of recurrence by about 50% and the risk of death by nearly 30%, based on evidence from five large phase III adjuvant trials.

Herceptin is now approved for use in combination with chemotherapy for the adjuvant treatment of HER-2-positive breast cancer, marking a significant advancement in the management of this previously challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Trastuzumab (Herceptin) in the adjuvant treatment of HER-2-positive early breast cancer]. Láng, I., Hitre, E.[2015]

In a study of 208 patients with advanced HER2-positive breast cancer receiving first-line anti-HER2 therapy for at least 1 year, the median overall survival was found to be 81 months, indicating long-term efficacy of the treatment.

The overall response rate to the therapy was 87.5%, with a median progression-free survival of 39.5 months, although 4.8% of patients experienced cardiotoxicity, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcome with targeted therapy in advanced/metastatic HER2-positive breast cancer: The Royal Marsden experience. Battisti, NML., Tong, D., Ring, A., et al.[2020]

HER2-targeted therapies, including trastuzumab and newer agents like lapatinib and pertuzumab, have significantly improved survival rates for patients with HER2-positive breast cancer, transforming it from a poor prognosis to a more manageable condition.

Current research is exploring the effectiveness of HER2-targeted treatments without chemotherapy and assessing the benefits of these therapies earlier in the treatment process, indicating a shift towards more personalized and effective management strategies for breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of HER2-positive breast cancer. Figueroa-Magalhães, MC., Jelovac, D., Connolly, R., et al.[2022]

Targeted anti-HER2 therapies have significantly improved disease control and survival rates in patients with metastatic HER2-positive breast cancer, which affects about 20% of breast cancer cases.

This review highlights the importance of these therapies as the standard of care for first-line treatment and discusses ongoing advancements aimed at addressing remaining challenges in treating this aggressive cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting HER2 in Advanced Breast Cancer. Zhu, X., Joy, AA.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05511844

NCT05511844 | Study of ORM-5029 in Subjects With ... Have histologically confirmed advanced breast cancer that is HER2+ by In Situ Hybridization (ISH) and/or at least 1+ staining by Immunohistochemistry (IHC), ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.TPS1114

A phase 1, first-in-human, open label, escalation and ... This phase 1 first-in-human study evaluates the safety, tolerability, and efficacy of ORM-5029 administered by intravenous infusion in patients (pts) with HER2 ...

3. aacrjournals.org aacrjournals.org/cancerres/article/82/12_Supplement/3933/703288/Abstract-3933-ORM-5029-A-first-in-class-targeted

Abstract 3933: ORM-5029: A first-in-class targeted protein ... Here, we describe the development of ORM-5029, a highly potent and selective GSPT1 degrader targeting HER2-expressing tumor cells.

4. withpower.com withpower.com/trial/phase-1-her2-positive-breast-cancer-9-2022-420b4

ORM-5029 for HER2-Positive Breast Cancer Research shows that targeting HER2 in breast cancer with specific therapies has significantly improved survival and disease control. Similar treatments, like ...

5. orumrx.com orumrx.com/news/vl3wn5a30fp37mmj9vnpr5m8kdd1rv

Orum Therapeutics Presents Preclinical Data At AACR ... ORM-5029 exhibits potent activity in HER2-low models both in vitro and in vivo. Dose-dependent efficacy of ORM-5029 correlates with robust and ...