Clinical trial NCT06305247: A Study to Assess IPN01194 When Administered Alone in Adults With Advanced Solid Tumours
Official title: An Open-label, Phase I/IIa First-in-human, Dose Escalation and Cohort Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetic, Pharmacodynamic and Antitumour Activity of ERK1/2 Inhibitor IPN01194 as Single Agent in Adult Participants With Advanced Solid Tumours
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Melanoma
Head and Neck Squamous Cell Carcinoma
Pancreatic Ductal Adenocarcinoma
Colorectal Cancer
Solid Tumor
Lead sponsor: Ipsen
Sponsor class: INDUSTRY
First posted: 2024-03-12
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Phase I is a dose escalation with backfill in participants with selected MAPKm advanced solid tumours.

Phase IIa (cohort expansion) is an open label randomised study.
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the appropriate dosage, safety and effectiveness of the study drug, IPN01194 in adults with advanced solid tumours.

The participants in this study will have advanced solid tumours. 'Advanced solid tumours' refers to cancers that can occur in several places, including cancers in organs or tissues that have spread from their original site to nearby tissues or other parts of the body.

In this study, all participants will receive the study drug, which will be taken by mouth (orally).

Detailed description: The study consists of two parts, called Phase I and Phase IIa.

Phase I is designed to assess the safety of increasing doses of IPN01194 in participants with specific types of advanced solid tumours.

The aim of this "dose escalation" phase is to find the dose range showing activity on the tumor that can be tolerated by the participants, and to determine the two doses for further testing in Phase IIa. Phase I will assess how the body processes and responds to the study drug when administered with and without food.

In Phase IIa, participants with selected single tumour type will be invited to take part. During this phase, the two dose levels of the study drug identified from Phase I will be tested. Participants will take the study drug one of the two dose levels. Each participant will be assigned to a dose level at random (by chance).

Each phase will consist of three periods:

1. A period to assess eligibility (screening period) that will take up to 28 days.
2. A treatment period of at least 28 days that will require at least two visits for the first month followed by one visit every month. There will be also one visit, at the end of treatment, at least 30 days after the last administration of study drug.
3. A follow-up period (Phase IIa participants only), where every 3 months, participants will be contacted by phone, until death or the study cut-off date, whichever comes first.

Participants will undergo blood samplings, urine collections, physical examinations, and clinical evaluations. They may continue some other medications, but the details need to be recorded.

If in the opinion of the investigator a participant is continuing to experience clinical benefit after the cut-off date, the participant may remain in the study and continue to receive the study drug until either disease progression, unacceptable toxicity or other withdrawal criteria are met.

Eligibility criteria: Inclusion Criteria :

* Participants must be ≥18 years of age
* Participants with histologically confirmed metastatic solid tumour (melanoma, metastatic colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC) or head and neck squamous cell carcinoma (HNSCC)) for whom no suitable alternative standard therapy exists.
* Participants must bear tumours harbouring selected classes of genetic mutations, (MAPKm).
* Participants must have measurable disease per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1
* Eastern Cooperative Oncology Group (ECOG)/performance status (PS) of 0 or 1.
* Participants must consent to the use of archival tumour tissue or, if not available, collection of fresh tumour biopsy at screening
* Male and female participants Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical trials.

Exclusion Criteria

* Gastrointestinal conditions that could impair absorption of IPN01194 or inability to swallow oral medications.
* Any evidence of severe active infection or inflammatory condition.
* Non-adequate cardiac function
* Have one or more of study defined ophthalmological findings/conditions
* Known psychiatric or substance abuse disorder, or any other cognitive disorder per the opinion of the investigator that would interfere with the participant's ability to cooperate with the requirements of the study.
* Underlying medical conditions that, in the investigator's or sponsor's opinion, will obscure the interpretation of toxicity determination or AEs.
* Known second malignancy within the last 2 years prior to first dose of study intervention..
* Major surgery within 28 days prior to first dose of study intervention.
* Ongoing AEs caused by any prior anti-cancer therapy ≥Grade 2 (National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0).
* Active brain metastases or leptomeningeal metastases
* Current enrolment or past participation in any other clinical trial involving an investigational study treatment within the last 28 days.
* Live vaccine(s) within 28 days prior to first dose of study intervention
* Concurrent treatment with any other anti-cancer therapy (including radiotherapy or investigational agents).
* Treatment with medications that prolong the QT/QTc interval.
* Treatment with strong and moderate CYP3A4 inducers
* Treatment with strong or moderate inhibitors of CYP3A4
* Only for Phase I participants assigned to dose escalation and low-dose backfill participants: treatment with proton pump inhibitors within 14 days prior to first dose of study intervention.
* Non-adequate bone marrow function
* Non-adequate renal function
* Non-adequate hepatic function
* Non adequate coagulation function.
* Known uncontrolled human immunodeficiency virus (HIV) infection or hepatitis B or C
* Sensitivity to IPN01194 or any of its components.

Primary outcomes:
measure: Phase 1: Percentage of participants with dose limiting toxicity (DLT)
timeFrame: Within 28 days of first dose
measure: Phase 1: Percentage of participants experiencing Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TE SAEs)
timeFrame: At 30 days following the last administration of study intervention
measure: Phase 1: Percentage of participants with dose interruptions and permanent treatment discontinuations
timeFrame: At 30 days following the last administration of study intervention
measure: Phase 2a: Objective response rate (ORR)
timeFrame: At end of treatment (up to approximately 32 months)
Secondary outcomes:
measure: Phase 1: Time to maximum observed drug concentration (Tmax) after single and multiple doses of IPN01194
timeFrame: At Day 1 and Day 15.
measure: Phase 1: Maximum observed drug concentration (Cmax) after single and multiple doses of IPN01194
timeFrame: At Day 1 and Day 15.
measure: Phase 1: Area under the plasma concentration time curve (AUCtau) after single and multiple doses of IPN01194
timeFrame: At Day 1 and Day 15.
measure: Phase 1: Geometric mean ratio of Cmax of IPN01194 administered in fed state relative to fasted state
timeFrame: Between Day -8 and Day -3 (fasted period) and between Day -10 and Day -7 (fed state period)
measure: Phase 1: Geometric mean ratio of AUClast of IPN01194 administered in fed state relative to fasted state
timeFrame: Between Day -8 and Day -3 (fasted period) and between Day -10 and Day -7 (fed state period)
measure: Phase 1: Geometric mean ratio of AUCinf administered in fed state relative to fasted state
timeFrame: Between Day -8 and Day -3 (fasted period) and between Day -10 and Day -7 (fed state period)
measure: Phase 1: Prolongation of corrected QT interval (QTc)
timeFrame: Within 28 days of first dose
measure: Phase 1: Objective response rate (ORR)
timeFrame: At end of treatment (up to approximately 32 months)
measure: Phase 2a: Duration of response (DoR)
timeFrame: From randomisation to end of treatment (up to approximately 32 months)
measure: Phase 2a: Progression-free survival (PFS)
timeFrame: From randomisation to end of treatment (up to approximately 32 months)
measure: Phase 2a: PFS rate at 4 months
timeFrame: From randomisation to 4 months
measure: Phase 2a: Disease control rate (DCR)
timeFrame: At end of treatment (up to approximately 32 months)
measure: Phase 2a: Percentage of participants with TEAEs and TE SAEs
timeFrame: At end of treatment (up to approximately 32 months)
measure: Phase 2a: Percentage of participants with dose interruptions and permanent treatment discontinuations
timeFrame: At end of treatment (up to approximately 32 months)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: The Angeles Clinic and Research Institute - California
state: California
city: San Diego
country: United States
facility: UC San Diego Health System - La Jolla
state: California
city: New Haven
country: United States
facility: Yale Cancer Center - New Heaven
state: Connecticut
city: Nashville
country: United States
facility: Sarah Cannon Research Institute (SCRI) - Nashville
state: Tennessee
city: Fairfax
country: United States
facility: Virginia Cancer Specialist
state: Virginia
city: Lyon
country: France
facility: Centre Léon Bérard - Lyon
city: Paris
country: France
facility: Paris Saint-Louis
city: Saint-Herblain
country: France
facility: Institut de Cancerologie de l'Ouest (St-Herblain)
city: Villejuif
country: France
facility: IGR-Villejuif
city: Barcelona
country: Spain
facility: Barcelona - Val D'Hebron
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz - Madrid
city: Madrid
country: Spain
facility: M.D. Anderson Cancer Center Madrid
Study officials:
affiliation: Ipsen
name: Ipsen Medical Director
role: STUDY_DIRECTOR
References: