ArticleJournal of hematology & oncology2021
Phase 1 study of M2698, a p70S6K/AKT dual inhibitor, in patients with advanced cancer.
Article in Journal of hematology & oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01971515 (A Phase I, First-in-Human, Dose Escalation Trial of MSC2363318A, a Dual p70S6K/Akt Inhibitor, in Subjects With Advanced Malignancies), which is not on this map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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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.
A Phase I, First-in-Human, Dose Escalation Trial of MSC2363318A, a Dual p70S6K/Akt Inhibitor, in Subjects With Advanced Malignancies
Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Lymphodepleting chemotherapy practices and effect on safety and efficacy outcomes in patients with solid tumours undergoing T cell receptor-engineered T cell (TCR-T) Therapy: a systematic review and meta-analysis.Cancer immunology, immunotherapy : CII · 2023Pooled it
- Review
- Targeting the Osteopontin-regulated PI3K/AKT signaling pathway: A molecular approach to overcome drug resistance and metastasis in gastrointestinal tumors.World journal of gastrointestinal oncology · 2025Review
- The current landscape of quinazoline derivatives withFuture medicinal chemistry · 2025Review
- HMGA2 and protein leucine methylation drive pancreatic cancer lineage plasticity.Nature communications · 2025Article
- Clinical application of PBMCs in breast cancer: detection, treatment evaluation and prognosis.Frontiers in cell and developmental biology · 2025Review
- p70S6K as a Potential Anti-COVID-19 Target: Insights from Wet Bench and In Silico Studies.Cells · 2024Article
- The Role of the PI3K/Akt/mTOR Axis in Head and Neck Squamous Cell Carcinoma.Biomedicines · 2024Review
- SRC inhibition enables formation of a growth suppressive MAGI1-PP2A complex in isocitrate dehydrogenase-mutant cholangiocarcinoma.Science translational medicine · 2024Article
- Molecular tumour boards - current and future considerations for precision oncology.Nature reviews. Clinical oncology · 2023Review
- Downregulation of pro-surfactant protein B contributes to the recurrence of early-stage non-small cell lung cancer by activating PGK1-mediated Akt signaling.Experimental hematology & oncology · 2023Article
- Orthologs of Human-Disease-Associated Genes in Plants Are Involved in Regulating Leaf Senescence.Life (Basel, Switzerland) · 2023Article
- Beyond controlling cell size: functional analyses of S6K in tumorigenesis.Cell death & disease · 2022Review
- AKT inhibition in the central nervous system induces signaling defects resulting in psychiatric symptomatology.Cell & bioscience · 2022Article
- MUC1 is a potential target to overcome trastuzumab resistance in breast cancer therapy.Cancer cell international · 2022Review
Corrections and comments
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Authors and funding
15 authors at 12 institutions in 3 countries.
Funding
Abstract
backgroundThe PI3K/AKT/mTOR (PAM) pathway is a key regulator of tumor therapy resistance. We investigated M2698, an oral p70S6K/AKT dual inhibitor, in patients with advanced cancer who failed standard therapies.
methodsM2698 was administered as monotherapy (escalation, 15-380 mg daily; food effect cohort, 240-320 mg daily) and combined with trastuzumab or tamoxifen.
resultsOverall, 101 patients were treated (M2698, n = 62; M2698/trastuzumab, n = 13; M2698/tamoxifen, n = 26). Patients were predominantly aged < 65 years, were female, had performance status 1 and were heavily pretreated. There was a dose- and concentration-dependent inhibition of pS6 levels in peripheral blood mononuclear cells and tumor tissue. M2698 was well tolerated; the most common treatment-emergent adverse events were gastrointestinal, abnormal dreams and fatigue (serious, attributed to M2698: monotherapy, 8.1%; M2698/trastuzumab, 7.7%; M2698/tamoxifen, 11.5% of patients). The recommended phase 2 doses of M2698 were 240 mg QD (monotherapy), 160 mg QD (M2698/trastuzumab) and 160 mg QD/240 mg intermittent regimen (M2698/tamoxifen). In the monotherapy cohort, 27.4% of patients had stable disease at 12 weeks; no objective response was noted. The median progression-free survival (PFS) durations in patients with PAM pathway alterations with and without confounding markers (KRAS, EGFR, AKT2) were 1.4 months and 2.8 months, respectively. Two patients with breast cancer (M2698/trastuzumab, n = 1; M2698/tamoxifen, n = 1) had partial response; their PFS durations were 31 months and 2.7 months, respectively.
conclusionsM2698 was well tolerated. Combined with trastuzumab or tamoxifen, M2698 demonstrated antitumor activity in patients with advanced breast cancer resistant to multiple standard therapies, suggesting that it could overcome treatment resistance. Trial registration ClinicalTrials.gov, NCT01971515. Registered October 23, 2013.
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