Phase 1completed; sponsor decided to change strategy to a combination study

This study is an open label, two-part, First in Human (FIH) Phase 1/2 dose-finding study designed to determine the safety, tolerability, Pharmacokinetics (PK), Pharmacodynamics (PD) and proof-of-concept (POC) of OMO-103 in patients with advanced solid tumours.

This study is an open label, two-part, FIH Phase 1/2 dose-finding study designed to determine the safety, tolerability, PK, PD and proof-of-concept of OMO-103 in patients with advanced solid tumours.

The study consists of two parts:

• Part 1: Dose escalation in patients with advanced solid tumours, including 5 OMO-103 dose levels.

Approximately 11 to 24 patients in total will be enrolled in Part 1, covering 5 dose levels with the primary objective of determining the safety and tolerability of OMO-103 and defining an appropriate dose for further evaluation in Part 2.

The study will start with an accelerated-titration dose-escalation scheme enrolling one evaluable patient per cohort for the first 2 dose levels followed by a classic 3+3 design.

• Part 2: Dose expansion where at least 3 parallel groups of patients with advanced Non Small Cell Lung Cancer (NSCLC), Triple Negative Breast Cancer (TNBC) and Colorectal Cancer (CRC) will be treated at the recommended Phase 2 dose (RP2D) of OMO-103 to further characterise the safety, tolerability, PK, PD and anti-tumour activity of OMO-103.

Approximately 18 patients will be enrolled in each of the 3 parallel groups of patients (NSCLC, TNBC, CRC) in Part 2.

Main Inclusion Criteria:

- Male or female patients, 18 years of age or older who sign the informed consent document, are willing and able to comply with the study protocol and have:

Part 1 (Dose Escalation):

- Histologically or cytologically proven advanced solid tumour for which there is no curative therapy and has progressed on Standard of Care (SOC) treatment or is intolerant to or has no available SOC or SOC unacceptable.

Part 2 (Dose Expansion):

- Histologically or cytologically proven advanced NSCLC whose tumours are KRAS-mutated and where the disease has progressed after a chemotherapy and immunotherapy regimen (at least two prior lines of standard therapy), advanced TNBC where the disease has progressed after having received anthracyclines and taxanes (at least two prior lines of standard therapy) and advanced CRC whose tumours are RAS mutated and where the disease has progressed after at least two prior lines of standard therapy.

Parts 1 and 2:

• Patient must have measurable disease as per RECIST v1.1 criteria
• Tumour biopsy (either from the primary tumour or from metastases) during Screening and during Treatment should be obtained from the patients, if feasible.
• Documented progression on or following the last line of therapy.
• ECOG performance status up to 1.
• Life expectancy of ≥12 weeks.
• Adequate organ function

Main Exclusion Criteria:

Parts 1 and 2:

• Systemic anti-cancer therapy within 4 weeks prior to study entry.
• Radiation therapy within 4 weeks prior to study entry. Localised palliative radiotherapy to non-target lesions is allowed.
• Non-malignant systemic disease including cerebrovascular accident (CVA), unstable angina pectoris, unstable atrial fibrillation, unstable cardiac arrhythmia, myocardial infarction in the last 6 months, New York Heart Association (NYHA) Class III or IV heart failure, coagulation abnormalities and clinically significant pulmonary compromise, particularly a requirement for supplemental oxygen use to maintain adequate oxygenation in the previous 6 months.
• Patients with a history of congenital or acquired immunodeficiency syndrome, or currently receiving immunosuppressive therapy >10 mg prednisolone or equivalent. Patients receiving inhaled or topical corticosteroids are eligible.
• Patients with symptomatic or unstable central nervous system (CNS) primary tumour or metastases and/or carcinomatous meningitis. Patients with documented treated CNS metastases stable for at least 4 weeks may be enrolled at the discretion of the Investigator.
• Patients with need of therapeutic anticoagulation.

AE were collected for each patient from signing informed consent until last follow-up which was in average 3 months but varied a lot from 4 day up to 536 days.

no deviation. CTCAE version 5 was used.