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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ipsen Pharma

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

27 Jun 2024 → ongoing

Decision date (initial)

2024-05-02

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Ipsen Pharma SAS

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Pharmacokinetic, Efficacy, Safety, Dose response, Others

1. Phase 1: Percentage of participants with dose limiting toxicity (DLT)
2. Phase 1: Percentage of participants experiencing treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TE SAEs).
3. Phase 1: Percentage of participants with dose interruptions and permanent treatment discontinuations
4. Phase 2a: Objective response rate (ORR)

Secondary objectives 14

1. Phase 1: Time to maximum observed drug concentration (Tmax) after single and multiple doses of IPN01194
2. Phase 1: Maximum observed drug concentration (Cmax) after single and multiple doses of IPN01194
3. Phase 1: Area under the plasma concentration time curve (AUCtau) after single and multiple doses of IPN01194.
4. Phase 1: Geometric mean ratio of Cmax of IPN01194 administered in fed state relative to fasted state
5. Phase 1: Geometric mean ratio of AUClast of IPN01194 administered in fed state relative to fasted state.
6. Phase 1: Geometric mean ratio of AUCinf administered in fed state relative to fasted state.
7. Phase 1: Prolongation of corrected QT interval (QTc).
8. Phase 1: Objective response rate (ORR).
9. Phase 2a: Duration of response (DoR).
10. Phase 2a: Progression-free survival (PFS).
11. Phase 2a: PFS rate at 4 months
12. Phase 2a: DCR (Disease control rate)
13. Phase 2a: Percentage of participants with TEAEs and TE SAEs
14. Phase 2a: Percentage of participants with dose interruptions and permanent treatment discontinuations

Conditions and MedDRA coding

Pancreatic Ductal Adenocarcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Participants must be ≥18 years of age
2. Participants with histologically confirmed metastatic solid tumour (melanoma, CRC, PDAC or HNSCC) for whom no suitable alternative standard therapy exists
3. Participants must bear tumours harbouring selected classes of genetic mutations, (MAPKm).
4. Participants must have measurable disease per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1
5. Eastern Cooperative Oncology Group (ECOG)/performance status (PS) of 0 or 1.
6. Participants must consent to the use of archival tumour tissue or, if not available, collection of fresh tumour biopsy at screening
7. 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 24

1. Gastrointestinal conditions that could impair absorption of IPN01194 or inability to swallow oral medications
2. Active brain metastases or leptomeningeal metastases
3. Current enrolment or past participation in any other clinical trial involving an investigational study treatment within the last 28 days
4. Live vaccine(s) within 28 days prior to first dose of study intervention
5. Concurrent treatment with any other anti-cancer therapy (including radiotherapy or investigational agents).
6. Treatment with medications that prolong the QT/QTc interval
7. Treatment with strong and moderate CYP3A4 inducers
8. Treatment with strong or moderate inhibitors of CYP3A4
9. 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.
10. Non-adequate bone marrow function
11. Non-adequate renal function
12. Any evidence of severe active infection or inflammatory condition
13. Non-adequate hepatic function
14. Non adequate coagulation function
15. Known uncontrolled human immunodeficiency virus (HIV) infection or hepatitis B or C
16. Sensitivity to IPN01194 or any of its components
17. Non-adequate cardiac function
18. Have one or more of study defined ophthalmological findings/conditions
19. 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
20. Underlying medical conditions that, in the investigator’s or sponsor’s opinion, will obscure the interpretation of toxicity determination or AEs
21. Known second malignancy within the last 2 years prior to first dose of study intervention
22. Major surgery within 28 days prior to first dose of study intervention
23. 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).
24. France-specific: participants under court protection, not affiliated to a social security system or protected adults.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Phase 1: Percentage of participants with dose limiting toxicity (DLT) [Time Frame: Cycle 1: Day 1 to Day 28]
2. 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. [Time Frame: From Cycle 1 Day 1 to 30 days following the last administration of study intervention]
3. Phase 1: Percentage of participants with dose interruptions and permanent treatment discontinuations [Time Frame: From Cycle 1 Day 1 to 30 days following the last administration of study intervention]
4. 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. [Time Frame: Cycle 1 Day 1 to 12 weeks (up to approximately 32 months)]

Secondary endpoints 14

1. Phase 1: Time to maximum observed drug concentration (Tmax) after single and multiple doses of IPN01194 [Time Frame: Cycle 1 Day 1 to Day 28]
2. Phase 1: Maximum observed drug concentration (Cmax) after single and multiple doses of IPN01194 [Time Frame: Cycle 1 Day 1 to Day 28]
3. 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. [Time Frame: Cycle 1 Day 1 to Day 28]
4. Phase 1: Geometric mean ratio of Cmax of IPN01194 administered in fed state relative to fasted state [Time Frame: From Day -10 to Day -1 before baseline (Cycle 1 Day 1)]
5. 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. [Time Frame: From Day -10 to Day -1 before baseline (Cycle 1 Day 1)]
6. 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. [Time Frame: From Day -10 to Day -1 before baseline (Cycle 1 Day 1)]
7. 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. [Time Frame: Cycle 1 Day 1 to Day 28]
8. 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). [Time Frame: Cycle 1 Day 1 to 12 weeks]
9. 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 [Time Frame: From randomisation to end of treatment (up to approximately 32 months)]
10. 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. [Time Frame: From randomisation to end of treatment (approximately 32 months)]
11. Phase 2a: PFS rate at 4 months [Time Frame: From randomisation to 4 months]
12. Phase 2a: DCR. DCR is defined as the percentage of participants with BOR of CR, PR or SD, as determined by investigator per RECIST version 1.1. [Time Frame: Cycle 1 Day 1 to end of treatment (approximately 32 months)]
13. Phase 2a: Percentage of participants with TEAEs and TE SAEs [Time Frame: Cycle 1 Day 1 to end of treatment (up to approximately 32 months)]
14. Phase 2a: Percentage of participants with dose interruptions and permanent treatment discontinuations [Time Frame: Cycle 1 Day 1 to end of treatment (up to approximately 32 months)]

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ipsen Pharma

Sponsor organisation

Ipsen Pharma

Address

70 Rue Balard

City

Paris

Postcode

75015

Country

France

Scientific contact point

Organisation

Ipsen Pharma

Contact name

Medical Development Director

Public contact point

Organisation

Ipsen Pharma

Contact name

Ipsen Clinical Study Enquiries

Third parties 11

Locations

2 EU/EEA countries · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications