Rigosertib Plus Pembrolizumab in Treating Patients With Unresectable/Metastatic Melanoma Refractory to PD-1 Inhibitors

NCT05764395 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: VICCMEL2218NCI-2023-01369
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II clinical trial tests how well rigosertib plus pembrolizumab workings in treating patients with melanoma which cannot be removed by surgery (unresectable) or that has spread from where it first started (primary site) to other places in the body (metastatic), and that has not responded to previous treatment with PD-1 or PD-L1 inhibitors (refractory). Rigosertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and may change the immune system to make immunotherapy more effective. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving rigosertib in combination with pembrolizumab may be more effective in treating patients with unresectable metastatic melanoma that has not responded to previous treatment with PD-1 or PD-L1 inhibitors than giving either drug alone.

Conditions

Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Metastatic Melanoma; Refractory Melanoma; Unresectable Melanoma

Outcome Measures

Primary Outcomes (1)

• Overall response rate

  Progression will be assessed as defined by Immune-Modified Response Evaluation Criteria in Solid Tumors criteria. PFS will be assessed using the Kaplan-Meier method. Median PFS and PFS at one year will be reported with 95% confidence intervals

  Up to 3 years

Secondary Outcomes (3)

• Progression free survival (PFS)

  Up to 3 years

• Incidence of adverse events

  Up to 30 days after the last dose of study intervention or before the initiation of a new anti-cancer treatment, whichever comes first

• Overall survival

  The interval between the first dose of pembrolizumab and death for any reason, assessed up to 3 years

Study Arms (1)

Treatment (Rigosertib, pembrolizumab)

EXPERIMENTAL

Patients receive rigosertib PO plus pembrolizumab IV throughout the study. Patients undergo CT or MRI and blood sample collection at screening and on study, and may also undergo tissue biopsy at screening and on study.

Drug: Rigosertib; Biological: Pembrolizumab; Procedure: Magnetic Resonance Imaging; Procedure: Biospecimen Collection; Procedure: Biopsy

Interventions

Rigosertib DRUG

Given by mouth

Treatment (Rigosertib, pembrolizumab)

Pembrolizumab BIOLOGICAL

Given by IV

Treatment (Rigosertib, pembrolizumab)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Treatment (Rigosertib, pembrolizumab)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Treatment (Rigosertib, pembrolizumab)

Biopsy PROCEDURE

Undergo tissue biopsy

Treatment (Rigosertib, pembrolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of unresectable or metastatic cutaneous melanoma will be enrolled in this study.
• Male participants: A male participant must agree to use a contraception during the treatment period and for at least 6 days (140 hours) plus an additional 90 days (a spermatogenesis cycle) after the last dose of study treatment and refrain from donating sperm during this period.
• Female participants: A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) OR
• A WOCBP who agrees to follow the contractive guidance during the treatment period and for at least 6 days (140 hours) plus 120 days after the last treatment dose of study.
• Participants must have progressed on treatment with an anti-PD-1/L1 monoclonal antibody (mAb) administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies. PD-1 inhibitor treatment progression is defined by meeting the following criteria:
• For patients treated with anti-PD-1/L1 mAb in the unresectable/metastatic setting:
• Has received at least 2 doses of an approved anti-PD-1/L1 mAb.
• Has demonstrated disease progression after anti-PD-1/L1 as defined by Immune-Modified Response Evaluation Criteria in Solid Tumors (iRECIST). The initial evidence of progressive disease (PD) is to be confirmed by a second assessment no less than 4 weeks from the date of the first documented disease progression, in the absence of rapid clinical progression.
• Progressive disease has been documented within 12 weeks from the last dose of anti-PD-1/L1 mAb.
• For patients treated with anti-PD-1/L1 mAb in the adjuvant setting:
• Has received at least 2 doses of an approved anti-PD-1/L1 mAb.
• Develops recurrent disease during active adjuvant treatment with anti-PD-1/L1 mAb, OR
• Develops recurrent disease within 6 weeks of last dose of anti-PD-1/L1 mAb.
• Progressive disease is determined according to iRECIST (ie, progression by Response Evaluation Criteria in Solid Tumors \[RECIST\] version \[v\]1.1 on first imaging, confirmed with repeat imaging performed at least 4 weeks later). Once disease progression is confirmed, the initial date of disease progression documentation will be considered the date of disease progression OR

You may not qualify if:

• Has a diagnosis of primary uveal or mucosal melanoma.
• A WOCBP who has a positive urine pregnancy test within 72 hours of the first dose of study intervention. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. In the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication. Pregnancy testing will be obtained every three months while on study treatment; patients will be withdrawn from the study if pregnancy occurs.
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks (for immunotherapeutic agents) or within 2 weeks (for targeted therapeutics) prior to the first dose of study drug. If a subject has experienced adverse events (AE) from prior treatment, he/she must have recovered from all AEs to \< grade 1 or baseline. Patients with \< grade 2 neuropathy may be eligible. Patients with endocrine-related AEs \< 2 requiring treatment or physiologic steroid replacement may be eligible.
• Has received prior radiotherapy within 2 weeks of the first dose of study drug. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=\< 2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
• If participant has had recent major surgery, the participant must has recovered adequately from the procedure and/or any complications from the surgery prior to the first dose of study drug.
• Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study drug. Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Participants with non-melanoma skin cancer (eg, basal cell carcinoma of the skin, squamous cell carcinoma of the skin) or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
• Subjects with untreated active central nervous system (CNS) metastases, active brain metastases or leptomeningeal metastatic foci. For the subjects with brain metastases, if they have received treatment and have no evidence of progressive disease on magnetic resonance imaging (MRI) at least 4 weeks after completion of the treatment and within 30 days prior to the first dose, they are eligible to participate in the study.
• Has a history of severe hypersensitivity (\>= grade 3), specifically infusion reaction or anaphylaxis to pembrolizumab and/or any of its excipients.
• Has a history of severe hypersensitivity (\>= grade 3 reactions including wheezing, rash, or hypotension) to rigosertib and/or any of its excipients (including polyethylene glycol), or anaphylaxis.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Has an active infection requiring systemic therapy.

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead

Study Sites (1)

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

ON 01910; pembrolizumab; Magnetic Resonance Spectroscopy; Biopsy

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative

Study Officials

• Douglas Johnson, MD

  Vanderbilt University/Ingram Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: February 28, 2023
• First Posted: March 10, 2023
• Study Start: May 9, 2023
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2029
• Last Updated: April 27, 2026

Record last verified: 2026-04

Locations

US (1)