Southwest Oncology Group S0826: A phase 2 trial of SCH 727965 (NSC 727135, dinaciclib) in patients with stage IV melanoma
Related Experiment Video
Updated: Jun 11, 2025
A Melanoma Patient-Derived Xenograft Model
Published on: May 20, 2019
Christopher D Lao1,2, James Moon3, Vincent T Ma4
1Rogel Cancer Center, University of Michigan Medical Center, Ann Arbor, Michigan, USA.
Background:
Cell cycle inhibition is an established therapeutic approach for some cancers. A multicenter, single-arm, phase 2 trial (ClinicalTrials.gov identifier NCT00937937) of the cyclin-dependent kinase inhibitor SCH 727965 (NSC 747135; dinaciclib) was conducted in patients with metastatic melanoma to determine its clinical activity.
Methods:
Patients with metastatic melanoma of cutaneous or mucosal origin were eligible if they had zero to one previous treatments, a Zubrod performance status of 0-1, and adequate organ function. SCH 727965 50 mg/m2 was given intravenously every 3 weeks until progression. Co-primary end points were 1-year overall survival (OS) and 6-month progression-free survival (PFS).
Results:
Seventy-two patients were enrolled from July 1, 2009, to November 1, 2010, at 24 institutions. Sixty-eight percent of patients had M1c disease, and 43% had elevated lactate dehydrogenase levels. Twenty-eight patients (39%) experienced grade 4 adverse events, including 20 cases of neutropenia. Sixty-seven patients were evaluable for response. There was a response in zero of 67 patients (95% confidence interval [CI], 0%-5%), and stable disease was observed in 21%. The estimated median PFS was 1.4 months (95% CI, 1.4-1.5 months), and the 6-month PFS rate was 6% (2%-13%). The median OS was 8.2 months (95% CI, 5.5-10.5 months), and the 1-year OS rate was 38% (95% CI, 26%-49%).
Conclusions:
This multicenter, US National Cancer Institute Cancer Therapy Evaluation Program-sponsored trial of SCH 727965 was conducted at a time when the current generation of effective therapies for melanoma were not available. Although the null hypothesis of 1-year OS was rejected, the minimal PFS impact and substantive toxicity indicated that this regimen lacks justification for further investigation as a single agent.
Insights
This study evaluated SCH 727965 for metastatic melanoma. While it showed some survival benefit, its limited progression-free survival and significant toxicity suggest it is not a viable single-agent therapy.
Area of Science:
- Oncology
- Clinical Pharmacology
Background:
- Cell cycle inhibition is a validated cancer treatment strategy.
- SCH 727965 (dinaciclib) is a cyclin-dependent kinase inhibitor.
- A phase 2 trial investigated dinaciclib in metastatic melanoma.
Purpose of the Study:
- To determine the clinical activity of SCH 727965 in patients with metastatic melanoma.
- To evaluate 1-year overall survival (OS) and 6-month progression-free survival (PFS) as co-primary end points.
Main Methods:
- A multicenter, single-arm, phase 2 trial enrolled patients with metastatic melanoma.
- SCH 727965 was administered intravenously at 50 mg/m² every 3 weeks.
- Eligibility criteria included limited prior treatment and adequate organ function.
Main Results:
- Seventy-two patients were enrolled; 67 were evaluable for response.
- No objective responses were observed (95% CI, 0%-5%); 21% had stable disease.
- Median PFS was 1.4 months; 6-month PFS rate was 6%. Median OS was 8.2 months; 1-year OS rate was 38%.
Conclusions:
- The trial met its primary endpoint for 1-year OS, rejecting the null hypothesis.
- However, the limited impact on progression-free survival and significant toxicity were noted.
- The regimen is not recommended for further investigation as a single agent for metastatic melanoma.
