Overview
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:
- A period to assess eligibility (screening period) that will take up to 28 days.
- 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.
- 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
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.