IPN01203 for adults with advanced or metastatic solid tumors after immune checkpoint therapy

An Open-label, Phase I/II First in Human, Dose Escalation, Optimisation and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Anti-tumour Activity of IPN01203 in Participants With Locally Advanced or Metastatic Solid Tumours Who Have Progressed on or After Immune Checkpoint Inhibitor Therapies

We will test whether the experimental drug IPN01203 is safe and can slow or stop tumor growth in adults with advanced or metastatic solid tumors who previously received immune checkpoint inhibitors.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 102 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Ipsen (Industry-sponsored)
• Drugs / interventions: radiation, prednisone
• Locations: 11 sites (Boston, Massachusetts and 10 other locations)
• Trial ID: NCT07213830 on ClinicalTrials.gov

What this trial studies

This multi-center, first-in-human Phase Ia/Ib trial uses dose escalation followed by dose optimization to study IPN01203 in adults with measurable locally advanced or metastatic solid tumors previously exposed to immune checkpoint inhibitors. Phase Ia will escalate doses to identify a tolerable and potentially active dose range, while Phase Ib will compare low- and high-dose schedules to further characterize safety, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary anti-tumor activity. The protocol includes RECIST v1.1 tumor imaging, routine labs, and close adverse event monitoring with dose decisions guided by observed toxicities and PK/PD data. A Phase II expansion cohort may be opened if early safety and activity signals support further testing.

Who should consider this trial

Good fit: Adults (≥18 years) with measurable locally advanced or metastatic solid tumors, ECOG performance status 0–1, prior exposure to immune checkpoint inhibitors, and recovery from acute treatment-related toxicities are the intended participants.

Not a fit: Patients with poor performance status (ECOG ≥2), rapidly declining health, uncontrolled comorbidities, or tumors that are not measurable by RECIST are unlikely to benefit from this early-phase trial.

Why it matters

Potential benefit: If successful, IPN01203 could offer a new treatment option that stabilizes or reduces tumor burden in patients whose cancers progressed after checkpoint inhibitor therapy.

How similar studies have performed: Some early-phase immuno-oncology agents and combination approaches have produced responses in subsets of patients, but IPN01203 is a novel compound and its clinical benefit has not yet been established.

Eligibility criteria

Inclusion Criteria:

* Participant must be ≥18 years of age, at the time of signing the informed consent.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
* Measurable disease per RECIST version 1.1 (at least one lesion that is measurable by RECIST 1.1. Tumour lesions in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions after radiation) and documented locally advanced or metastatic disease with CT and/or MRI.
* All acute, clinically significant (CS) treatment-related AEs from a prior therapy resolved to Grade 1 or lower prior to study entry. Participants with chronic toxicities such as Grade ≤2 neuropathy or alopecia can be included.
* Have a life expectancy for disease-related mortality, as evaluated by the investigator.
* 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 studies.
* Adequate haematologic and end organ function
* Participant is capable of giving signed informed consent as described in the protocol.

Exclusion Criteria:

* Have untreated or active primary brain tumour, Central Nervous System (CNS) metastases, leptomeningeal disease, or spinal cord compression.
* Experienced severe, life-threatening immune-mediated AEs, or infusion-related reactions such as those that lead to permanent discontinuation while on treatment with prior anticancer therapy such as immune checkpoint inhibitor therapy.
* History of known autoimmune disease
* History of stroke or significant cerebrovascular disease, encephalitis, meningitis, organic brain disease (e,g., Parkinson's disease) or uncontrolled seizures in the year prior to first dose of study drug.
* History of CS cardiac disease within 6 months prior to the initiation of study intervention, including but not limited to unstable angina, acute myocardial infarction, endoscopic or open-heart cardiac surgery, or heart failure classified as New York Heart Association Grade 2 or higher. Additional exclusion criteria include:

  1. Left ventricular ejection fraction \<45%
  2. QT interval corrected by Fridericia (QTcF) \>470 ms (for women) and \>450 ms (for men) or CS arrhythmias.
* History of CS respiratory disease within 6 months prior to the initiation of study intervention, including severe chronic obstructive pulmonary disease or asthma.
* Prior organ transplantation.
* Chronic or ongoing active infections within 4 weeks prior to Cycle1 Day1 (C1D1).
* Presence of hepatitis B surface antigen (HBsAg) \[or hepatitis B core antibody (HBcAb)\] at screening or within 3 months prior to the first dose of study intervention.
* Positive hepatitis C antibody test result at screening or within 3 months prior to the first dose of study intervention.
* Participants with known history of HIV infection are excluded from the study unless they meet the following criteria:

  1. Stable Antiretroviral Therapy: Participants must be on a stable antiretroviral therapy regimen for at least 4 weeks prior to enrolment.
  2. CD4+ T cell Count: Participants must have a CD4+ T cell count of at least 200 cells/µL.
  3. Viral Load: Participants must have an undetectable viral load (HIV RNA \<50 copies/mL)
  4. No Opportunistic Infections: Participants must not have had any opportunistic infections or other human immunodeficiency virus (HIV)-related illness within the past 6 months Note: HIV testing will be performed in any countries where it is mandatory per local requirements.
* History of other malignancy within the last years.
* Significant concurrent, uncontrolled medical condition that would put participants at unacceptable risk from study participation or preclude them from complying with study procedures per investigator including, but not limited to renal, hepatic, haematologic, gastrointestinal, endocrine, pulmonary, neurological, cerebral, or psychiatric disease.
* Treatment with \>10 mg per day of prednisone (or equivalent) or other immune suppressive drugs within 7 days prior to the initiation of study drug. Exceptions may be made for participants who have had allergic reaction to iodinated contrast media. Steroids for topical, ophthalmic, inhaled, or nasal administration are allowed.
* Concurrent participation in another therapeutic treatment study.
* Participants accommodated in an institution because of regulatory or legal order; prisoners or participants who are legally institutionalised.
* For French participants only: participants are under court protection, not affiliated to a social security system or protected adults.

Where this trial is running

Boston, Massachusetts and 10 other locations

• Dana-Farber Cancer Institute — Boston, Massachusetts, United States (Not_yet_recruiting)
• START MidWest PI Sharma — Grand Rapids, Michigan, United States (Recruiting)
• Sarah Cannon Research Institute PI McKean Nasville, TN, USA — Nashville, Tennessee, United States (Recruiting)
• MD Anderson PI Champiat — Houston, Texas, United States (Not_yet_recruiting)
• Start San Antonio PI Rasco — San Antonio, Texas, United States (Recruiting)
• NEXT PI Spira — Fairfax, Virginia, United States (Not_yet_recruiting)
• Princess Margaret Cancer Center PI Spreafico — Toronto, Canada (Recruiting)
• Gustave Roussy Cancer Campus Grand Paris- (Institut de Cancerologie Gustave-Roussy) - PI Ronan — Villejuif, France (Not_yet_recruiting)
• Hospital Universitario Vall d'Hebron PI Garralda Cabanas — Barcelona, Spain (Not_yet_recruiting)
• NEXT Quiron-Barcelona - PI Saavedra Santa Gadea — Barcelona, Spain (Recruiting)
• START Madrid - CIOCC. Grupo Hospital de Madrid (HM) - Centro Integral Oncologico Clara Campal (CIOCC) - Calvo Aller — Madrid, Spain (Recruiting)

Study contacts

• Study coordinator: Ipsen Clinical Study Enquiries

Conditions Advanced Solid Tumor; Metastatic Solid Tumor