Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2023
A Phase I/II Trial of Oral SRA737 (a Chk1 Inhibitor) Given in Combination with Low-Dose Gemcitabine in Patients with Advanced Cancer.
Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05827614 (An Open-Label, Multicenter, First-in-Human, Dose-Escalation and Dose-Expansion, Phase 1/2 Study of BBI-355 and BBI-355 in Combination With Select Targeted Therapies in Subjects With Locally Advanced or Metastatic Solid Tumors With Oncogene Amplifications), which is not on this map. Cited by 34 papers.
What it found
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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.
An Open-Label, Multicenter, First-in-Human, Dose-Escalation and Dose-Expansion, Phase 1/2 Study of BBI-355 and BBI-355 in Combination With Select Targeted Therapies in Subjects With Locally Advanced or Metastatic Solid Tumors With Oncogene Amplifications
Who cites it
34 citing papers in PubMed, 37 citations in OpenAlex.
- A Phase 1/2 trial of SRA737 (a Chk1 inhibitor) administered orally in patients with advanced cancer.British journal of cancer · 2023Trial
- Synthetic lethality in cancer: mechanisms, therapeutic exploitation and clinical translation.Signal transduction and targeted therapy · 2026Review
- Genomic characterization of ER-positive primary tumors and corresponding relapses identifies potentially targetable alterations.NPJ breast cancer · 2026Article
- Ataxia telangiectasia mutated (ATM) kinase as a predictive biomarker in clinical oncology: implications for a precision treatment approach.Neoplasia (New York, N.Y.) · 2026Review
- Radiogenomics and the DNA damage response: opportunities for biomarker-guided radiosensitization in pancreatic cancer.Frontiers in oncology · 2026Review
- The CHK1 inhibitor Prexasertib is effective againstFrontiers in endocrinology · 2026Article
- CHK1 as a Metabolic and Immunological Regulator: Implications for Cancer Therapy.Oncology research · 2026Review
- Lysine demethylase 5D promotes CHEK1 inhibitor sensitivity through p38-mediated cyclooxygenase-2 expression in castration-resistant prostate cancer cells.The Journal of pharmacology and experimental therapeutics · 2025Article
- Pancreatic cancer in 2025: Have we found a solution?World journal of gastroenterology · 2025Review
- Targeting DNA Damage Repair Pathways Beyond PARP Inhibition.Targeted oncology · 2025Review
- ARHGAP11A, a member of Rho GTPase activating protein family, as a prognostic biomarker linked to DNA damage response across pan-cancer.BMC cancer · 2025Article
- Advances in cervical cancer: current insights and future directions.Cancer communications (London, England) · 2025Review
- Clinical outcomes of DNA-damaging agents and DNA damage response inhibitors combinations in cancer: a data-driven review.Frontiers in oncology · 2025Article
- Interplay of replication stress response and immune microenvironment in high-grade serous ovarian cancer.Frontiers in cell and developmental biology · 2025Review
- Pancreatic cancer: failures and hopes-a review of new promising treatment approaches.Exploration of targeted anti-tumor therapy · 2025Review
- Targeting the DNA damage response in cancer.MedComm · 2024Review
- The Potential for Targeting GCancers · 2024Review
- Small cell lung cancer: emerging subtypes, signaling pathways, and therapeutic vulnerabilities.Experimental hematology & oncology · 2024Review
- Emerging advances in defining the molecular and therapeutic landscape of small-cell lung cancer.Nature reviews. Clinical oncology · 2024Review
- Article
Corrections and comments
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Authors and funding
16 authors at 15 institutions in 4 countries.
Funding
Abstract
purposeThis was a Phase I/II trial of the novel checkpoint kinase 1 (Chk1) inhibitor SRA737 given in combination with gemcitabine. Its objectives were to establish the safety profile, recommended Phase 2 dose (RP2D), pharmacokinetics profile, and clinical activity of SRA737. PATIENTS AND
methodsPatients with advanced solid tumors were enrolled into dose-escalation cohorts and treated in 28-day cycles with oral SRA737 on days 2, 3, 9, 10, 16, and 17, and intravenous gemcitabine on days 1, 8, and 15. Treatment was continued until progression. Each expansion cohort included up to 20 patients with specific genetically defined tumors.
resultsThe RP2D was determined to be 500 mg SRA737 combined with low-dose (250 mg/m2) gemcitabine. Of 143 enrolled patients, 77 were treated at doses of at least 500 mg SRA737 combined with 250 mg/m2 gemcitabine. Common toxicities of nausea, vomiting, fatigue, and diarrhea were primarily mild to moderate, and rarely led to treatment discontinuation. Anemia, neutropenia, and thrombocytopenia were grade ≥3 in 11.7%, 16.7%, and 10% of patients treated at the RP2D, respectively. The objective response rate (ORR) was 10.8% overall and notably the ORR in anogenital cancer was 25%. Partial tumor responses were observed in anogenital cancer, cervical cancer, high-grade serous ovarian cancer, rectal cancer, and small cell lung cancer.
conclusionsSRA737 in combination with low-dose gemcitabine was well tolerated with lower myelotoxicity than has been seen at standard doses of gemcitabine or with other combinations of Chk1 inhibitors with gemcitabine. Tumor responses were observed in anogenital and other solid tumors.
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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.