ArticleClinical cancer research : an official journal of the American Association for Cancer Research2022
Initial Phase I Safety Study of Gedatolisib plus Cofetuzumab Pelidotin for Patients with Metastatic Triple-Negative Breast Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Prevalence of antibody drug conjugated-induced nausea and vomiting (ADCINV) in patients with cancer.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2026Pooled it
- Cancer signaling networks in tumor progression and drug resistance: Crosstalk, adaptive reprogramming and therapeutic targeting (Review).Oncology reports · 2026Review
- Antibody-drug conjugates in breast cancer: Progress and future directions.Cell reports. Medicine · 2026Review
- Targeting cancer signaling pathways and their therapeutic strategies.Discover oncology · 2026Review
- Review
- Therapeutic targeting of the protein tyrosine kinase-7 in cancer: an overview.The oncologist · 2025Review
- Review
- Sortilin-Mediated Rapid, Precise and Sustained Degradation of Membrane Proteins via mRNA-Encoded Lysosome-Targeting Chimera.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Divide and Conquer-Targeted Therapy for Triple-Negative Breast Cancer.International journal of molecular sciences · 2025Review
- USP8-mediated PTK7 promotes PIK3CB-related pathway to accelerate the malignant progression of non-small cell lung cancer.Thoracic cancer · 2025Article
- Article
- PI3K/AKT/mTOR signaling pathway: an important driver and therapeutic target in triple-negative breast cancer.Breast cancer (Tokyo, Japan) · 2024Review
- PTK7: an underestimated contributor to human cancer.Frontiers in oncology · 2024Review
- Exploring the therapeutic potential of ADC combination for triple-negative breast cancer.Cellular and molecular life sciences : CMLS · 2023Review
- The mechanisms of class 1A PI3K and Wnt/β-catenin coupled signaling in breast cancer.Biochemical Society transactions · 2023Review
- Review
- Targeting the PI3K/AKT/mTOR and RAF/MEK/ERK pathways for cancer therapy.Molecular biomedicine · 2022Review
- Emergence of Nanotechnology as a Powerful Cavalry against Triple-Negative Breast Cancer (TNBC).Pharmaceuticals (Basel, Switzerland) · 2022Review
- PI3K Inhibitors in Cancer: Clinical Implications and Adverse Effects.International journal of molecular sciences · 2021Review
- Aberrant WNT/CTNNB1 Signaling as a Therapeutic Target in Human Breast Cancer: Weighing the Evidence.Frontiers in cell and developmental biology · 2020Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
purposeThe PI3K pathway is dysregulated in the majority of triple-negative breast cancers (TNBC), yet single-agent inhibition of PI3K has been ineffective in TNBC. PI3K inhibition leads to an immediate compensatory upregulation of the Wnt pathway. Dual targeting of both pathways is highly synergistic against TNBC models in vitro and in vivo. We initiated a phase I clinical trial combining gedatolisib, a pan-class I isoform PI3K/mTOR inhibitor, and cofetuzumab pelidotin, an antibody-drug conjugate against the cell-surface PTK7 protein (Wnt pathway coreceptor) with an auristatin payload. PATIENTS AND
methodsParticipants (pt) had metastatic TNBC or estrogen receptor (ER) low (ER and PgR < 5%, HER2-negative) breast cancer, and had received at least one prior chemotherapy for advanced disease. The primary objective was safety. Secondary endpoints included overall response rate (ORR), clinical benefit at 18 weeks (CB18), progression-free survival (PFS), and correlative analyses.
resultsA total of 18 pts were enrolled in three dose cohorts: gedatolisib 110 mg weekly + cofetuzumab pelidotin 1.4 mg/kg every 3 weeks (n = 4), 180 mg + 1.4 mg/kg (n = 3), and 180 mg + 2.8 mg/kg (n = 11). Nausea, anorexia, fatigue, and mucositis were common but rarely reached ≥grade 3 severity. Myelosuppression was uncommon. ORR was 16.7% (3/18). An additional 3 pts had stable disease (of these 2 had stable disease for >18 weeks); CB18 was 27.8%. Median PFS was 2.0 months (95% confidence interval for PFS: 1.2-6.2). Pts with clinical benefit were enriched with genomic alterations in the PI3K and PTK7 pathways.
conclusionsThe combination of gedatolisib + cofetuzumab pelidotin was well tolerated and demonstrated promising clinical activity. Further investigation of this drug combination in metastatic TNBC is warranted.
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