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

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06305247
• Other study ID #: CLIN-01194-450
• Secondary ID: 2023-506228-10-0
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: April 3, 2024
• Est. completion date: March 20, 2028

Study information

• Verified date: May 2024
• Source: Ipsen
• Contact: Ipsen Clinical Study Enquiries
• Phone: See e mail
• Email: clinical.trials[@]ipsen.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 220
• Est. completion date: March 20, 2028
• Est. primary completion date: March 20, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Colorectal Cancer
• Head and Neck Squamous Cell Carcinoma
• Melanoma
• Pancreatic Ductal Adenocarcinoma
• Solid Tumor
• Squamous Cell Carcinoma of Head and Neck

Intervention

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.
• 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

Locations

Country	Name	City	State
France	Centre Léon Bérard - Lyon	Lyon
France	Paris Saint-Louis	Paris
France	Institut de Cancerologie de l'Ouest (St-Herblain)	Saint-Herblain
France	IGR-Villejuif	Villejuif
Spain	Barcelona - Val D'Hebron	Barcelona
Spain	Fundacion Jimenez Diaz - Madrid	Madrid
Spain	M.D. Anderson Cancer Center Madrid	Madrid
United States	Virginia Cancer Specialist	Fairfax	Virginia
United States	The Angeles Clinic and Research Institute - California	Los Angeles	California
United States	Sarah Cannon Research Institute (SCRI) - Nashville	Nashville	Tennessee
United States	Yale Cancer Center - New Heaven	New Haven	Connecticut
United States	UC San Diego Health System - La Jolla	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Ipsen

Countries where clinical trial is conducted

United States,  France,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1: Percentage of participants with dose limiting toxicity (DLT)		Within 28 days of first dose
Primary	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
Primary	Phase 1: Percentage of participants with dose interruptions and permanent treatment discontinuations		At 30 days following the last administration of study intervention
Primary	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	Phase 1: Time to maximum observed drug concentration (Tmax) after single and multiple doses of IPN01194		At Day 1 and Day 15.
Secondary	Phase 1: Maximum observed drug concentration (Cmax) after single and multiple doses of IPN01194		At Day 1 and Day 15.
Secondary	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.
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Phase 2a: PFS rate at 4 months		From randomisation to 4 months
Secondary	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)
Secondary	Phase 2a: Percentage of participants with TEAEs and TE SAEs		At end of treatment (up to approximately 32 months)
Secondary	Phase 2a: Percentage of participants with dose interruptions and permanent treatment discontinuations		At end of treatment (up to approximately 32 months)