An Open-label, Phase I/II First in Human, Dose Escalation, Optimisation and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Anti-tumour Activity of IPN01203 in Participants With Locally Advanced or Metastatic Solid Tumours Who Have Progressed on or After Immune Checkpoint Inhibitor Therapies

The primary objective of this study is to evaluate the safety and tolerability of IPN01203 administered as a single agent and to determine the maximum tolerated dose (MTD) and maximum administered dose (MAD) in participants with selected advanced or metastatic solid tumours who have progressed on or after immune checkpoint inhibitor therapies during Phase Ia. In Phase Ib, the primary objective is to determine the optimal dosing regimen of IPN01203 in selected tumours. These objectives are clinically relevant for establishing the therapeutic window and appropriate dosing strategy for IPN01203 in this treatment-refractory patient population.

The secondary objectives include: • Phase Ia: To characterise single and multiple dose pharmacokinetics (PK) of IPN01203 • To assess the immunogenicity potential of IPN01203 • To assess the preliminary clinical benefit of IPN01203 by evaluation of anti-tumour activity • Phase Ib: To assess clinical activity of IPN01203 as a single agent in participants with selected advanced or metastatic solid tumours • To further assess the immunogenicity potential of IPN01203

The sponsor did not provide information regarding the total number of participants enrolled in this clinical trial. The study population includes **adult participants** aged 18 years and older with **advanced solid tumors** or **metastatic solid tumors**. Both **male** and **female** participants are eligible for enrollment. Participants must have an **ECOG performance status** of 0 to 1, indicating they are fully ambulatory or have restricted physically strenuous activity but are capable of light work. The trial requires **measurable disease** according to **RECIST version 1.1** criteria, with documented locally advanced or metastatic disease confirmed by **CT** and/or **MRI** imaging. Participants must have adequate hematologic and end organ function, and any acute, clinically significant treatment-related adverse events from prior therapy must be resolved to Grade 1 or lower. Participants with chronic toxicities of moderate intensity (Grade ≤2) that are stable and well controlled may be included. A vulnerable population is included in this trial. Male and female participants must use appropriate contraceptive methods consistent with local regulations. All participants must be capable of providing signed informed consent.

This is an open-label, Phase I/II, first-in-human study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and anti-tumour activity of IPN01203 in participants with locally advanced or metastatic solid tumours who have progressed on or after immune checkpoint inhibitor therapies. The study consists of two phases: Phase Ia involves dose escalation to determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) of IPN01203 as a single agent, while Phase Ib focuses on dose optimisation to establish the optimal dosing regimen in selected tumour types. The trial is not randomised or blinded, and all participants will receive the investigational medicinal product IPN01203, which is administered as a solution for infusion via intravenous infusion. The active substance is a protein-based agent, and the product is manufactured by IPSEN PHARMA.

The estimated recruitment start date is January 15, 2026, with an anticipated study completion date of July 14, 2032, indicating an overall trial duration of approximately 6.5 years. Participant involvement will vary depending on individual response to treatment and tolerability, but participants will remain in the study until disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-defined criteria for discontinuation are met. During Phase Ia, the primary endpoints include the percentage of participants experiencing dose-limiting toxicity (DLT) and the percentage of participants with treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TE SAEs). In Phase Ib, the primary endpoint is objective response rate (ORR), defined as the percentage of participants achieving a complete response (CR) or partial response (PR) according to RECIST version 1.1 criteria as assessed by the investigator.

Secondary endpoints encompass pharmacokinetic parameters, including time to maximum observed drug concentration (Tmax), maximum observed drug concentration (Cmax), and area under the plasma concentration-time curve (AUCtau) after single and multiple doses. Immunogenicity will be assessed by measuring the percentage of treatment-emergent anti-drug antibodies (TEADA), including binding and neutralizing antibodies. Additional efficacy endpoints include duration of response (DoR), duration of stable disease (SD), progression-free survival (PFS), disease control rate (DCR), and time to response (TTR). DoR is measured from the first documented evidence of CR or PR until progressive disease or death. PFS is defined as the time from the first administration of IPN01203 to the first documented disease progression per RECIST version 1.1 or death from any cause. DCR represents the percentage of participants with a best overall response of CR, PR, or SD.

Eligible participants must be at least 18 years of age at the time of informed consent and have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Participants must have measurable disease according to RECIST version 1.1, with at least one measurable lesion documented by computed tomography (CT) or magnetic resonance imaging (MRI). Tumour lesions in previously irradiated areas are considered measurable if progression has been demonstrated following radiation. All acute, clinically significant treatment-related adverse events from prior therapy must have resolved to Grade 1 or lower before study entry, although participants with stable chronic toxicities of moderate intensity (Grade ≤2) that are well controlled may be included. Participants must have adequate haematologic and end-organ function and a life expectancy sufficient for disease-related evaluation as determined by the investigator. Male and female participants must use contraception consistent with local regulations for clinical study participation. Participants must be capable of providing signed informed consent as described in the study protocol.

Study visits will include a screening visit to assess eligibility criteria, followed by treatment visits during which IPN01203 will be administered and safety, pharmacokinetic, pharmacodynamic, and efficacy assessments will be conducted. Follow-up visits will be scheduled to monitor ongoing response, disease progression, and long-term safety. The end-of-study visit will occur when participants discontinue treatment due to disease progression, unacceptable toxicity, withdrawal of consent, or completion of the study protocol. Early termination from the study may occur if participants experience unacceptable toxicity, disease progression, withdrawal of informed consent, investigator decision, pregnancy, non-compliance with study procedures, or death. The study aims to provide comprehensive data on the safety profile, pharmacological characteristics, and clinical activity of IPN01203 in the target patient population with advanced or metastatic solid tumours previously treated with immune checkpoint inhibitors.

The experimental treatment in this clinical trial consists of **IPN01203**, a **solution for infusion** containing the active substance IPN01203, which is classified as a protein-based therapeutic agent. The product is manufactured by IPSEN PHARMA and is administered via **intravenous infusion**. This investigational medicinal product serves as the test treatment in the study and is being evaluated in participants with locally advanced or metastatic solid tumours who have progressed on or after immune checkpoint inhibitor therapies.

The study employs a dose escalation and optimization approach across two phases. During **Phase Ia**, the primary objective is to evaluate the safety and tolerability of IPN01203 as a single agent and to determine the **maximum tolerated dose** (MTD) or **maximum administered dose** (MAD) in participants with selected tumours. In **Phase Ib**, the focus shifts to determining the optimal dosing regimen of IPN01203 in selected tumour types. The specific dosage amounts, frequency of administration, and treatment duration will be established through the dose escalation and optimization phases of the trial. This is a first-in-human study designed to assess the **safety**, **tolerability**, **pharmacokinetics**, **pharmacodynamics**, **immunogenicity**, and anti-tumour activity of the investigational product.

Efficacy will be assessed through distinct endpoints for each phase of the study. In Phase Ia, the primary efficacy endpoint is **objective response rate (ORR)**, evaluated as a secondary measure, defined as the percentage of participants with best overall response of **complete response** or **partial response**, as determined by investigator per RECIST version 1.1. In Phase Ib, ORR serves as the primary efficacy endpoint, defined as the percentage of participants with best overall response of complete response or partial response, as determined by investigator per RECIST version 1.1.

Secondary efficacy endpoints include **duration of response (DoR)**, defined as the time from first documented evidence of complete response or partial response until **progressive disease**, as determined by investigator per RECIST version 1.1, or death from any cause, whichever occurs first. Duration of **stable disease** is defined as the time from the date of first IPN01203 administration to the date of the first documented disease progression, as determined by investigator per RECIST version 1.1, or death due to any cause, whichever occurs first, for participants with stable disease as best response, with a minimum stable disease duration of 8 weeks. **Progression-free survival (PFS)** is defined as the time from the date of first IPN01203 administration to the date of the first documented disease progression, as determined by investigator per RECIST version 1.1, or death due to any cause, whichever occurs first. **Disease control rate (DCR)** is defined as the percentage of participants with best overall response of complete response, partial response, or stable disease, as determined by investigator per RECIST version 1.1, from the first IPN01203 administration throughout the study. **Time to response (TTR)** is defined as the time between date of start of treatment until first documented response (complete response or partial response), as determined by investigator per RECIST version 1.1. Disease assessment will be performed using CT and/or MRI, with measurable disease defined per RECIST version 1.1.