Clinical trial · Interventional
Trial of MEK Inhibitor and PI3K/mTOR Inhibitor in Subjects With Locally Advanced or Metastatic Solid Tumors
An Open-Label, Phase Ib Dose Escalation Trial of Oral Combination Therapy With MSC1936369B and SAR245409 in Subjects With Locally Advanced or Metastatic Solid Tumors
NCT01390818CI-TRIAL-00026339completedPhase 1Results postedClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
This research trial is testing a combination of two experimental drugs, MSC1936369B (Mitogen-activated protein extracellular signal-regulated kinase (MEK) Inhibitor) and SAR245409 (Phosphatidylinositol 3-kinase (Pi3K)/Mammalian Target of Rapamycin (mTOR) inhibitor), in the treatment of locally advanced or metastatic solid tumors. The primary purpose of the study is to determine the maximum tolerated dose of the drug combination.
Conditions
Conditions (6)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Breast Cancer | Malignant Breast Neoplasm | CURATED_EXACT | 0.92 |
| Colorectal Cancer | Malignant Colorectal Neoplasm | CURATED_BROADER | 0.80 |
| Locally Advanced Solid Tumor | Solid Neoplasm | CURATED_BROADER | 0.80 |
| Melanoma | Melanoma | ONTOLOGY_EXACT | 0.98 |
| Metastatic Solid Tumor | Solid Neoplasm | CURATED_BROADER | 0.80 |
| Non Small Cell Lung Cancer | Lung Non-Small Cell Carcinoma | ALIAS | 0.90 |
Interventions
Interventions (2)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| MSC1936369B (pimasertib) | Drug | — | UNRESOLVED |
| SAR245409 (PI3K and mTOR inhibitor) | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- MSC1936369B and SAR245409 once daily
- interventionNames
- Drug: MSC1936369B (pimasertib)
- Drug: SAR245409 (PI3K and mTOR inhibitor)
- type
- EXPERIMENTAL
- label
- MSC1936369B and SAR245409 twice daily
- interventionNames
- Drug: MSC1936369B (pimasertib)
- Drug: SAR245409 (PI3K and mTOR inhibitor)
Primary outcomes (1)
- measure
- Number of Subjects With Dose Limiting Toxicities (DLT)
- timeFrame
- Day 1 up to Day 16 in cycle 1
- description
- DLT was defined as any of the following toxicities experienced during the first cycle of treatment at any dose level (DL) and judged not to be related to the underlying disease or any concomitant medication by the Investigator and/or the Sponsor: A treatment emergent adverse event (TEAE) of potential clinical significance such that further dose escalation (DE) would have exposed subjects to unacceptable risk. Any Grade greater than or equal to (\>=) 3 non-hematological toxicity, except for: Grade 3 diarrhea, nausea and vomiting with a duration less than or equal to (\<=) 48 hours despite adequate supportive care and Alopecia. Grade 4 neutropenia of \> 5 days duration or febrile neutropenia. Grade 3 thrombocytopenia with bleeding or Grade 4 thrombocytopenia. Any treatment interruption \> 2 weeks due to AEs not related to the underlying disease or concomitant medication at any dose level and any severe, life-threatening impairing daily functions complication or abnormality.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
- Maximum age
- 82 Years
Show eligibility criteria text
Inclusion Criteria: * Subject with advanced solid tumors for which there is no approved therapy: * Advanced solid tumor with diagnosed alteration in one or more of the following genes (PTEN, BRAF, KRAS, NRAS, PI3KCA, ErbB1, ErbB2, MET, RET, c-KIT, GNAQ, GNA11 and/or * A histologically or cytologically confirmed diagnosis of one of the following solid tumors: pancreatic, thyroid, colorectal, non-small cell lung, endometrial, renal, breast, ovarian carcinoma and melanoma * Subject with archived tumor tissue available for transfer to the Sponsor * Subject enrolled at lower dose level cohorts and MTD expansion cohorts must have tumor available for biopsy and agree to pre-treatment and on-treatment tumor biopsies * Subject has measurable or evaluable disease by response evaluation criteria in solid tumors (RECIST) v1.1 * Subject is aged greater than or equal to (\>=) 18 years * Subjects enrolled in disease specific expansion cohorts must fulfill all the inclusion/exclusion criteria listed above with the following restriction to the Inclusion Criterion number 1: * Relapsed or refractory Kirsten rat sarcoma viral oncogene homolog (KRAS) or neuroblastoma RAS viral oncogene homolog (NRAS) mutated metastatic non-small cell lung cancer (NSCLC) with no approved therapies, or * Relapsed or refractory metastatic triple negative breast cancer defined as estrogen, progesterone and HER2 negative carcinoma of the breast with no approved therapies, or * Relapsed or refractory metastatic colorectal cancer (CRC) with dual KRAS and PIK3CA mutation with no approved therapies, or * BRAF V600E/K mutated unresectable or metastatic melanoma after progression on B-Raf proto-oncogene, serine/threonine kinase (BRAF) inhibitors * Other protocol-defined inclusion criteria could apply Exclusion Criteria: * Subject has been previously treated with a PI3K inhibitor or a MEK inhibitor and taken off treatment due to treatment related adverse events * Subject has received: * Chemotherapy, immunotherapy, hormonal therapy, biologic therapy, or any other anti-cancer therapy within 28 days of trial drug treatment * Any investigational agent within 28 days of trial drug treatment * Extensive prior radiotherapy on more than 30% bone marrow reserves, or prior bone marrow/stem cell transplantation * Subject has not recovered from toxicity due to prior therapy * Subject has poor organ and marrow function as defined in the protocol * Subject has a history of central nervous system metastases, unless subject has been previously treated for CNS metastases * Subject has a history of difficulty swallowing, malabsorption or other chronic gastrointestinal disease * Subject has a history of recent major surgery or trauma within the last 28 days. * Subject has participated in another clinical trial within the past 30 days * Other protocol-defined exclusion criteria could apply
References
Publications (0)
Data not yet available
No reference posted for this study.