Clinical trial · Interventional
M8891 First in Human in Solid Tumors
An Open-label, Phase I Dose Escalation Trial of Methionine Aminopeptidase 2 Inhibitor M8891 in Subjects With Advanced Solid Tumors
NCT03138538CI-TRIAL-00057058M8891terminatedPhase 1Results postedClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Why stopped (as posted): As part of a portfolio-level management of the company's oncology pipeline, it was decided to stop the next phase of internal development of the MetAP2 (M8891) program to enable realization of other opportunities within the oncology portfolio.
Summary
Brief summary (as posted)
The purpose of this study was to determine the maximum tolerated dose (MTD), safety, tolerability, Pharmacokinetic (PK), pharmacodynamic and clinical activity of M8891 as single agent in participants with advanced solid tumors in Part 1.
Conditions
Conditions (2)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Advanced Solid Tumors | Solid Neoplasm | CURATED_BROADER | 0.80 |
| Metastatic Renal Cell Carcinoma | Renal Cell Carcinoma | CURATED_BROADER | 0.80 |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Part 1: M8891 | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (6)
- type
- EXPERIMENTAL
- label
- M8891 7 mg
- description
- Participant received M8891 at dose of 7 milligrams (mg) orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
- interventionNames
- Drug: Part 1: M8891
- type
- EXPERIMENTAL
- label
- M8891 12 mg
- description
- Participant received M8891 at dose of 12 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
- interventionNames
- Drug: Part 1: M8891
- type
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: * Participants must be refractory to or intolerant of existing cancer therapy(ies) known to provide clinical benefit. * Histologically confirmed advanced solid tumors with no clear curative treatment options available after at least 1 prior systemic anticancer therapy. * Tumor accessible for biopsies and agreement to conduct pre-dose and post-dose fresh tumor biopsies. * Male or female subjects at least 18 years of age * Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 at Screening * Histologic or cytologic evidence/proven of metastatic renal cell carcinoma (mRCC) with clear cell component * Part 2A: Participants should have progressed to 1 or more previous lines of systemic anticancer therapy, excluding treatment with cabozantinib * Part 2B: Participants should have progressed to 1 or 2 previous lines of systemic anticancer therapy, excluding treatment with cabozantinib. Participants should have failed to only 1 previous TKI for metastatic disease. Adjuvant therapy with sunitinib will be considered as 1 line of therapy for metastatic disease in the case that disease progression occurs during or within 3 months of the completion of the treatment. * Other protocol defined inclusion criteria could apply Exclusion Criteria: * ECOG PS \>= 2 * Extensive prior radiotherapy on more than 30% of bone marrow reserves, or prior bone marrow/stem cell transplantation within 5 years of study start. * Severe bone marrow, renal or liver impairment. * Tumor in contact with, invading or encasing major blood vessels or radiographic evidence of significant cavitary pulmonary lesions * Uncontrolled hypertension defined as sustained Blood Pressure (BP) \> 150 millimeters of mercury (mm Hg) systolic or \> 100 mm Hg diastolic despite optimal antihypertensive treatment * Participant is pregnant or breastfeeding * Part 2A and 2B: Previous use of cabozantinib or a MetAP2 inhibitor, tumor in contact with invading or encasing major blood vessels or radiographic evidence of significant cavitary pulmonary lesions * Other protocol defined exclusion criteria could apply
References
Publications (2)
- DERIVEDLignet F, Friese-Hamim M, Jaehrling F, El Bawab S, Rohdich F. Preclinical Pharmacokinetics and Translational Pharmacokinetic/Pharmacodynamic Modeling of M8891, a Potent and Reversible Inhibitor of Methionine Aminopeptidase 2. Pharm Res. 2023 Dec;40(12):3011-3023. doi: 10.1007/s11095-023-03611-z. Epub 2023 Oct 5. PMID 37798538
- DERIVEDCarducci MA, Wang D, Habermehl C, Bodding M, Rohdich F, Lignet F, Duecker K, Karpenko O, Pudelko L, Gimmi C, LoRusso P. A First-in-human, Dose-escalation Study of the Methionine Aminopeptidase 2 Inhibitor M8891 in Patients with Advanced Solid Tumors. Cancer Res Commun. 2023 Aug 24;3(8):1638-1647. doi: 10.1158/2767-9764.CRC-23-0048. eCollection 2023 Aug. PMID 37637935