Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2024
Phase I/II Study of Combined BCL-xL and MEK Inhibition with Navitoclax and Trametinib in KRAS or NRAS Mutant Advanced Solid Tumors.
Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02079740 (An Open Label, Two-Part, Phase Ib/II Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of the MEK Inhibitor Trametinib and the BCL2-Family Inhibitor Navitoclax), which is not on this map. Cited by 32 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
An Open Label, Two-Part, Phase Ib/II Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of the MEK Inhibitor Trametinib and the BCL2-Family Inhibitor Navitoclax (ABT-263) in Combination in Subjects With KRAS or NRAS Mutation-Positive Advanced Solid Tumors
Who cites it
32 citing papers in PubMed, 34 citations in OpenAlex.
- Review
- Hallmarks of the ageing lung: 10 years later.The European respiratory journal · 2026Review
- Regulated cell death programs shaping cancer therapy.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Article
- Decoding Senescence-Driven Heterogeneity in Early-Onset Colorectal Cancer for Prognostic and Therapeutic Stratification.Cancer science · 2026Article
- Exploring the Anti-Cervical Cancer Effect and Hepatotoxicity Risk of Gossypol Based on Untargeted Metabolomics and Network Toxicology.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Differential Preclinical Efficacy of Combined CDK4/6 and MEK Inhibition in Low-Grade Serous Ovarian Carcinoma Based onInternational journal of molecular sciences · 2026Article
- BCL-2 and BCL-xL in Cancer: Regulation, Function, and Therapeutic Targeting.International journal of molecular sciences · 2026Review
- PROTAC-mediated degradation of Bcl-xL potentiates target therapy in preclinical melanoma models.Journal of experimental & clinical cancer research : CR · 2026Article
- Impact of treatment history on drug resistance of metastatic colorectal cancer organoids.iScience · 2025Article
- Targeting the BCL2 Family: Advances and Challenges in BH3 Mimetic-Based Therapies.International journal of molecular sciences · 2025Review
- Evaluating Potential Therapeutic Targets and Drug Repurposing Based on the Esophageal Cancer Subtypes.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Direct Co-Targeting of Bcl-xL and Mcl-1 Exhibits Synergistic Effects in AR-V7-Expressing CRPC Models.Cancer research communications · 2025Article
- Functional Features of Senescent Cells and Implications for Therapy.International journal of molecular sciences · 2025Review
- Vascular senescence and aging: mechanisms, clinical implications, and therapeutic prospects.Biogerontology · 2025Review
- Anti-senescence therapies: a new concept to address cardiovascular disease.Cardiovascular research · 2025Review
- Review
- Recent Anti-KRASCancers · 2025Review
- Targeting KRAS-mutant pancreatic cancer through simultaneous inhibition of KRAS, MEK, and JAK2.Molecular oncology · 2025Article
- Cellular senescence in colorectal cancer: its occurrence, effect and therapy.Frontiers in oncology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
31 authors at 5 institutions in 4 countries.
Funding
Abstract
purposeMEK inhibitors (MEKi) lack monotherapy efficacy in most RAS-mutant cancers. BCL-xL is an anti-apoptotic protein identified by a synthetic lethal shRNA screen as a key suppressor of apoptotic response to MEKi. PATIENTS AND
methodsWe conducted a dose escalation study (NCT02079740) of the BCL-xL inhibitor navitoclax and MEKi trametinib in patients with RAS-mutant tumors with expansion cohorts for: pancreatic, gynecologic (GYN), non-small cell lung cancer (NSCLC), and other cancers harboring KRAS/NRAS mutations. Paired pretreatment and day 15 tumor biopsies and serial cell-free (cf)DNA were analyzed.
resultsA total of 91 patients initiated treatment, with 38 in dose escalation. Fifty-eight percent had ≥3 prior therapies. A total of 15 patients (17%) had colorectal cancer, 19 (11%) pancreatic, 15 (17%) NSCLC, and 32 (35%) GYN cancers. The recommended phase II dose (RP2D) was established as trametinib 2 mg daily days 1 to 14 and navitoclax 250 mg daily days 1 to 28 of each cycle. Most common adverse events included diarrhea, thrombocytopenia, increased AST/ALT, and acneiform rash. At RP2D, 8 of 49 (16%) evaluable patients achieved partial response (PR). Disease-specific differences in efficacy were noted. In patients with GYN at the RP2D, 7 of 21 (33%) achieved a PR and median duration of response 8.2 months. No PRs occurred in patients with colorectal cancer, NSCLC, or pancreatic cancer. MAPK pathway inhibition was observed in on-treatment tumor biopsies. Reductions in KRAS/NRAS mutation levels in cfDNA correlated with clinical benefit.
conclusionsNavitoclax in combination with trametinib was tolerable. Durable clinical responses were observed in patients with RAS-mutant GYN cancers, warranting further evaluation in this population.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.