A Study to Assess IPN01194 When Administered Alone in Adults With Advanced Solid Tumours

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

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).

Study Overview

• Status: Recruiting
• Conditions: Melanoma; Colorectal Cancer; Solid Tumor; Head and Neck Squamous Cell Carcinoma; Pancreatic Ductal Adenocarcinoma
• Intervention / Treatment: Drug: IPN01194; Drug: IPN01194

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.

• Study Type: Interventional
• Enrollment (Estimated): 220
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Ipsen Clinical Study Enquiries; Phone Number: See e mail; Email: clinical.trials@ipsen.com

Study Locations

• France
  • Lyon, France
    • Not yet recruiting
    • Centre Léon Bérard - Lyon
  • Paris, France
    • Not yet recruiting
    • Paris Saint-Louis
  • Saint-Herblain, France
    • Not yet recruiting
    • Institut de Cancerologie de l'Ouest (St-Herblain)
  • Villejuif, France
    • Not yet recruiting
    • IGR-Villejuif
• Spain
  • Barcelona, Spain
    • Not yet recruiting
    • Barcelona - Val D'Hebron
  • Madrid, Spain
    • Not yet recruiting
    • Fundacion Jimenez Diaz - Madrid
  • Madrid, Spain
    • Not yet recruiting
    • M.D. Anderson Cancer Center Madrid
• United States
  • California
    • Los Angeles, California, United States, 90025
      • Not yet recruiting
      • The Angeles Clinic and Research Institute - California
    • San Diego, California, United States, 92037
      • Not yet recruiting
      • UC San Diego Health System - La Jolla
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Not yet recruiting
      • Yale Cancer Center - New Heaven
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Sarah Cannon Research Institute (SCRI) - Nashville
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Virginia Cancer Specialist

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase I (Dose Escalation with Backfilling); Nine dose levels are planned to be tested.	Drug: IPN01194; IPN01194 will be taken orally over a period of 28 days (a "Cycle") at the assigned dose level. The dose limiting toxicity (DLT) observation period consists of the first 28 days of treatment with IPN01194 (Cycle 1). Participants will receive IPN01194 treatment beyond Cycle 1 until treatment is precluded by toxicity, disease progression, or upon participant's request or investigator decision.; Drug: IPN01194; All participants will receive IPN01194 orally for 28-day cycles at one of the two dose levels determined at the end of Phase I. Participants will receive IPN01194 treatment until treatment is precluded by toxicity, disease progression, or upon participant's request or investigator decision
Experimental: Phase IIa (Cohort Expansion); Study intervention will be administered at one of two doses of interest determined at the end of Phase I.	Drug: IPN01194; IPN01194 will be taken orally over a period of 28 days (a "Cycle") at the assigned dose level. The dose limiting toxicity (DLT) observation period consists of the first 28 days of treatment with IPN01194 (Cycle 1). Participants will receive IPN01194 treatment beyond Cycle 1 until treatment is precluded by toxicity, disease progression, or upon participant's request or investigator decision.; Drug: IPN01194; All participants will receive IPN01194 orally for 28-day cycles at one of the two dose levels determined at the end of Phase I. Participants will receive IPN01194 treatment until treatment is precluded by toxicity, disease progression, or upon participant's request or investigator decision

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Percentage of participants with dose limiting toxicity (DLT)		Within 28 days of first dose
Phase 1: Percentage of participants experiencing Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TE SAEs)	An Adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.	At 30 days following the last administration of study intervention
Phase 1: Percentage of participants with dose interruptions and permanent treatment discontinuations		At 30 days following the last administration of study intervention
Phase 2a: Objective response rate (ORR)	Defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) as determined by investigator.	At end of treatment (up to approximately 32 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Time to maximum observed drug concentration (Tmax) after single and multiple doses of IPN01194		At Day 1 and Day 15.
Phase 1: Maximum observed drug concentration (Cmax) after single and multiple doses of IPN01194		At Day 1 and Day 15.
Phase 1: Area under the plasma concentration time curve (AUCtau) after single and multiple doses of IPN01194	AUCtau is defined as the concentration of drug over one dosing interval.	At Day 1 and Day 15.
Phase 1: Geometric mean ratio of Cmax of IPN01194 administered in fed state relative to fasted state		Between Day -8 and Day -3 (fasted period) and between Day -10 and Day -7 (fed state period)
Phase 1: Geometric mean ratio of AUClast of IPN01194 administered in fed state relative to fasted state	AUClast is defined as the concentration of drug from time zero to the last observable concentration.	Between Day -8 and Day -3 (fasted period) and between Day -10 and Day -7 (fed state period)
Phase 1: Geometric mean ratio of AUCinf administered in fed state relative to fasted state	AUCinf is defined as the concentration of drug extrapolated to infinite time.	Between Day -8 and Day -3 (fasted period) and between Day -10 and Day -7 (fed state period)
Phase 1: Prolongation of corrected QT interval (QTc)	Prolongation of QTc defined as the upper limit of 90% confidence interval for change from baseline QTc evaluated over Cycle 1 at the highest clinically relevant exposure.	Within 28 days of first dose
Phase 1: Objective response rate (ORR)	The ORR is defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR).	At end of treatment (up to approximately 32 months)
Phase 2a: Duration of response (DoR)	Defined as the percentage of participants with BOR of CR or PR, as determined by investigator per RECIST version 1.1	From randomisation to end of treatment (up to approximately 32 months)
Phase 2a: Progression-free survival (PFS)	PFS is defined as the time from the date of randomisation to the date of the first documented disease progression, as determined by investigator per RECIST version 1.1.	From randomisation to end of treatment (up to approximately 32 months)
Phase 2a: PFS rate at 4 months		From randomisation to 4 months
Phase 2a: Disease control rate (DCR)	DCR is defined as the percentage of participants with BOR of CR, PR or stable disease (SD), as determined by investigator per RECIST version 1.1.	At end of treatment (up to approximately 32 months)
Phase 2a: Percentage of participants with TEAEs and TE SAEs		At end of treatment (up to approximately 32 months)
Phase 2a: Percentage of participants with dose interruptions and permanent treatment discontinuations		At end of treatment (up to approximately 32 months)

Collaborators and Investigators

• Sponsor: Ipsen
• Investigators: Study Director: Ipsen Medical Director, Ipsen

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2024
• Primary Completion (Estimated): March 20, 2028
• Study Completion (Estimated): March 20, 2028

Study Registration Dates

• First Submitted: February 27, 2024
• First Submitted That Met QC Criteria: March 8, 2024
• First Posted (Actual): March 12, 2024

Study Record Updates

• Last Update Posted (Actual): June 28, 2024
• Last Update Submitted That Met QC Criteria: June 27, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
• Other Study ID Numbers: CLIN-01194-450; 2023-506228-10-00 (Other Identifier: Ipsen)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications.

Patient level data will be anonymized and study documents will be redacted to protect the privacy of study participants.

Any requests should be submitted to www.vivli.org for assessment by an independent scientific review board

• IPD Sharing Time Frame: Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and EU or after the primary manuscript describing the results has been accepted for publication, whichever is later.
• IPD Sharing Access Criteria: Access Criteria: Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No