Sponsor Decision

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.

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.