Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Rigosertib Sodium, oral rigosertib, ON 01910.Na, SyB L-1101, ON 01910.Na Concentrate, ON 01910
Rigosertib · 22 trials · 37 indications
Bone marrow blast response is defined as bone marrow (BM) complete response, ≥ 50% BM blast decrease from pretreatment value, or stable BM response (no progression) according to the International Working Group (IWG) 2006 criteria and overall survival. Overall survival is defined as the time from first study treatment to death from any cause. All patients will be followed until death and/or progression, even if they have discontinued treatment for whatever cause. Survival time of patients lost to follow-up will be censored at the time they were last known to be alive.
This study's primary outcome is overall survival, defined as the time from randomization to death from any cause. All patients will be followed until death. Patients lost to follow-up will be censored at the time last known alive.
Overall survival (OS) is defined as the time from randomization to death from any cause. All patients will be followed until death or progression, even if they have discontinued treatment for whatever cause. Patients lost to follow-up will be censored at the time last known alive. The OS primary analysis will compare the active ON 01910.Na regimen to BSC once a total number of 223 deaths has been reached.
The number of patients who achieve hematologic improvement will be documented. Hematologic improvement is defined by the 2006 International Working Group (IWG) response criteria for the erythroid, platelet and neutrophil lineages.
Outcome is defined as the number of patients with Complete Response (CR) or Partial Response (PR) per revised Response Evaluation Criteria In Solid Tumors (RECIST 1.1). Complete response (CR) is defined as disappearance of all target lesions. Partial Response (PR) is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Number of units of red blood cell transfusions will be compared with the pretreatment transfusion number in the previous 8 weeks.
The Overall Response Rate is defined as the proportion of patients who achieve a Complete Response, a Partial Response, A Complete Bone Marrow Response or a Hematologic Improvement (HI) according to the 2006 International Working Group (IWG) criteria.
The NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 will be used to determine the grade of adverse events.
Progression-free survival, defined as the number of days from the first day of study drug dosing to the day of documented disease progression or death, as assessed using RECIST (Response Evaluation Criteria in Solid Tumors) guidelines according to Therasse P, Arbuck SF, Eisenhauer EA, et al. (2000) J Natl Cancer Inst. 92:205-216. Progressive disease is defined as at least a 20% increase in the sum of the longest diameter (LD)of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
MTD is defined as the highest dose for which at most 1 patient out of 6 experiences a dose-limiting toxicity (DLT)
The primary objective of the study is to determine the maximum tolerated dose (MTD) of oral rigosertib when administered with platinum-based chemoradiotherapy to patients with intermediate- and high-risk Head and Neck Squamous Cell Carcinoma. The MTD is defined as the dose level immediately below that at which 2 or more patients experience a dose limiting toxicity (DLT).
Dose Limiting Toxicity is defined as Grade 3 or greater non-hematological toxicity or stomatitis and/or esophagitis/dysphagitis lasting longer than 3 days.
Adverse events will be coded using the most recent version of the Medical Dictionary for Regulatory Activities (MedDRA) and summarized by system organ class (SOC), preferred term (PT), and worst Common Terminology Criteria for Adverse Events (CTCAE) Version 4 grade per patient.
Adverse events will be coded using the most recent version of the Medical Dictionary for Regulatory Activities (MedDRA) and summarized by system organ class (SOC), preferred term (PT), and worst Common Terminology Criteria for Adverse Events (CTCAE) Version 4 grade per patient.
The following time points will be used to collect samples to determine the AUC on Day 1 and 15: Pre-dose the first dose of the day and at 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, and 8.0 hour post dose the first dose of the day.
The following time points will be used to collect samples to determine the Cmax on Day 1 and 15: Pre-dose the first dose of the day and at 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, and 8.0 hour post dose the first dose of the day.
DLT: adverse event possibly related that is: * Grade ≥ 3 non-hematological toxicity other than nausea, vomiting, diarrhea, fever, esophagitis/dysphagia * Grade ≥ 3 nausea and vomiting uncontrolled by antiemetics; grade ≥ 3 diarrhea uncontrolled by antidiarrheal agents; grade ≥ 3 drug-induced fever uncontrolled by antipyretics; grade ≥3 metabolic abnormalities that are not controlled by optimal supportive care measures * Grade ≥ 3 stomatitis and/or esophagitis/dysphagia lasting \> 3 days * Marrow cellularity \<5% on day 42 or later (6 weeks) from start of therapy without evidence of leukemia
Determine the clinical response rate (complete or partial remission) according to response criteria in patients with relapsed/refractory acute myeloid or lymphocytic leukemia (1 Cheson BD, Bennett JM, Kopecky KJ, et al. Revised Recommendations of the International Working Group for Diagnosis, Standardization or Response Criteria, Treatment Outcomes and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. JCO 21:4642, 2003).
Adverse events (AEs) will be regarded as treatment emergent signs and symptoms (TESS) if they started on or after the date and time of administration of the first dose of study drug, or if they were present prior to the administration of the first dose of study drug and increased in severity during the study. Adverse events include clinical laboratory parameters (e.g., Hematology Panel and Serum Chemistry Panel). Other safety parameters include vital signs, physical examination findings, concomitant medications, and drug exposure.
Incidence of adverse signs and/or symptoms (adverse events and laboratory parameters)
MTD will be defined as the highest dose level of ON 01910.Na at which none of the first three patients or no more than one of six patients experienced dose limiting toxicity (DLT) in course 1.
DLTs are defined as: * Grade 3 non-hematological toxicity other than nausea, vomiting, diarrhea, fever, stomatitis, esophagitis/dysphagia. * Grade 3 nausea and vomiting uncontrolled by antiemetics; Grade 3 diarrhea uncontrolled by antidiarrheal agents; Grade 3 drug-induced fever uncontrolled by antipyretics. * Grade 3 stomatitis and/or esophagitis/dysphagia lasting \>3 days. * Grade 4 neutropenia or thrombocytopenia lasting \>5 days. * Episode of neutropenic fever, as defined in Protocol. * Failure to recover neutrophils (\>1,500 per microliter) or platelets (\>75,000 per microliter) by day 28.
Safety assessments will be based on medical review of adverse event reports and the results of vital sign measurements, physical examinations, and clinical laboratory tests. Results will be reported as an aggregate of the adverse events using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0 terminology and grading.
| Arm | Type | Description |
|---|---|---|
| rigosertib sodium | EXPERIMENTAL | Rigosertib sodium will be administered as a 72-hr continuous intravenous infusion consisting of 3 consecutive doses of 1800 mg over 24 hours on Days 1, 2, and 3 of a 14-day cycle for the first 8 cycles and then on Days 1, 2, and 3 of a 28-day cycle for the following cycles. |
| Arm A: Combination | EXPERIMENTAL | Arm A: Gemcitabine, 1000 mg/m2 weekly for 3 weeks of a 4 week cycle, + ON 01910.Na, 1800 mg/m2 via 2 hr CIV infusions administered twice weekly for 3 weeks of a 4 week cycle. |
| Arm B: Gemcitabine only | ACTIVE_COMPARATOR | Arm B: Gemcitabine only, 1000 mg/m2 weekly for 3 weeks of a 4 week cycle. |
| ON 01910.Na + best supportive care (BSC) | EXPERIMENTAL | Patients will receive ON 01910.Na 1800 mg/24 hr as a continuous intravenous infusion for 72 hours every other week for the first 16 weeks then every 4 weeks afterwards and best supportive care (BSC). |
| Best supportive care (BSC) | NO_INTERVENTION | Patients will receive best supportive care (BSC). |
| Oral rigosertib | EXPERIMENTAL | Patients will take 560 mg oral rigosertib (two 280 mg capsules) in the morning and 280 mg (one 280 mg capsule) in the afternoon, in fasting conditions, for 21 consecutive days of 21-day cycle (continuous regimen). |
| rigosertib | EXPERIMENTAL | Oral rigosertib capsules at a dose of 560 mg twice a day for 14 consecutive days of a 21-day cycle (2 weeks on, 1 week off regimen). |
| 21-Day Regimen | EXPERIMENTAL | 560 mg oral rigosertib in the morning and 280 mg rigosertib in the afternoon on days 1 to 21 of 21-day cycle |
| 800 mg/m^2 ON 01910.Na | EXPERIMENTAL | 800 mg/m\^2 ON 01910.Na administered as a continuous intravenous infusion (CIV) over 24 hours for 48 hours (i.e. 2 consecutive 24-hour infusions) every week for the first 3 weeks of 4-week cycle. |
| 1800 mg ON 01910.Na | EXPERIMENTAL | 1800 mg ON 01910.Na administered as a continuous intravenous infusion (CIV) over 24 hours for 72 hours (i.e., 3 consecutive 24-hour infusions) every 2 weeks for the first four 2-week cycles and every 4 weeks afterwards. |
| ON 01910.Na | EXPERIMENTAL | 3200 mg ON 01910.Na administered intravenously over 2 hours on days 1, 4, 8, 11, 15, and 18 of 28-day cycle |
| Rigosertib + Nivolumab | EXPERIMENTAL | Rigosertib + Nivolumab in metastatic KRAS+ lung adenocarcinoma patients |
| Rigosertib + Cisplatin + Radiation | EXPERIMENTAL | Oral rigosertib will be started 7 days before initiation of concurrent treatment with cisplatin and radiation therapy and will be administered on a continuous basis for a fixed duration of 8 weeks. Three oral rigosertib escalating doses will be sequentially evaluated: 70 mg 3 times a day (TID), 140 mg TID and 280 mg TID. Cisplatin will be administered intravenously at a dose of 40 mg/m\^2 on Days 1, 8, 15, 22, 29, 36, and 43 of the 7-week concurrent treatment course. The prescribed radiotherapy dose will be 70 Gray (Gy) in 2 Gy once-daily fraction size (total of 35 fractions) over the 7-week concurrent treatment course. The initial target volume encompassing the gross and subclinical disease sites will receive 2.0 Gy per fraction, 5 fractions per week. |
| Oral rigosertib plus azacitidine | EXPERIMENTAL | Oral rigosertib will be administered twice a day in fasting conditions for weeks 1, 2, and 3 of a 4-week cycle. Starting on Day 1 of second week (Day 8) of the cycle, azacitidine will be administered by subcutaneous injection or intravenous infusion at the labeled daily dose of 75 mg/m2, for 7 days. |
| gemcitabine and ON 01910.Na | EXPERIMENTAL | - |
| A | EXPERIMENTAL | Treatment of escalating doses of ON 01910.Na in combination with irinotecan |
| B | EXPERIMENTAL | Treatment of escalating doses of ON 01910.Na in combination with oxaliplatin |
| Treatment (rigosertib sodium) | EXPERIMENTAL | Patients receive rigosertib sodium either oral or IV over a 52 week period. Patients will take oral rigosertib continuously for a total of three weeks, every four-week cycle (three weeks on, one week off drug). For IV, rigosertib is administered as a 72-hr continuous infusion on Days 1, 2 and 3 of a 2-week cycle for the first eight 2-week cycles, then on Days 1, 2 and 3 of a 4-week cycle thereafter. |
| Name | Type | Description |
|---|---|---|
| rigosertib sodium | DRUG | - |
| ON 01910.Na | DRUG | ON 01910.Na, 1800 mg/m2 via 2 hr CIV infusions administered twice weekly for 3 weeks of a 4 week cycle. |
| Gemcitabine | DRUG | Gemcitabine 1000 mg/m2 weekly for 3 weeks of a 4 week cycle. |
| Oral rigosertib | DRUG | Dose of 560 mg consists of two (2) 280 mg soft gel capsules of rigosertib. |
| rigosertib | DRUG | Oral rigosertib capsules at a dose of 560 mg twice a day for 14 consecutive days of a 21-day cycle (2 weeks on, 1 week off regimen). |
| Nivolumab | DRUG | Nivolumab will be dosed once ever 2 weeks (twice per 28-day cycle; standard fixed dose of 240mg). |
| cisplatin | DRUG | - |
| Radiotherapy | RADIATION | - |
| Azacitidine | DRUG | Starting on Day 1 of second week (Day 8) of the cycle, azacitidine will be administered by subcutaneous injection or intravenous infusion at the labeled daily dose of 75 mg/m2, for 7 days. |
| ON 01910.Na and irinotecan | DRUG | ON 01910.Na will be administered by IV infusion over 24 hours once per week in a 6-week cycle (6 doses per cycle). The dose of ON 01910.Na will start at 250 mg/m2 and will proceed to higher dose levels after safety evaluation. The suggested starting dose of Irinotecan is 180 mg/m2 administered by intravenous (IV) infusion over 90 minutes every 2 weeks of a 6-week cycle (3 doses per cycle). Reductions in the starting doses according to recommendations of current approved prescribing information may be considered after review of patients' medical histories and potential tolerances to treatment with the chemotherapy agent. |
| ON 01910.Na and oxaliplatin | DRUG | ON 01910.Na will be administered by IV infusion over 24 hours once per week in a 6-week cycle (6 doses per cycle). The dose of ON 01910.Na will start at 250 mg/m2 and will proceed to higher dose levels after safety review of the combination regimen in the previous cohort. The suggested starting dose of Oxaliplatin is 85 mg/m2 administered by IV infusion over 120 minutes every 2 weeks of a 6-week cycle (3 doses per cycle). Reductions in the starting doses according to recommendations of current approved prescribing information may be considered after review of patients' medical histories and potential tolerances to treatment with the chemotherapy agent. |
| Quality-of-Life Assessment | OTHER | Ancillary studies |
Inclusion Criteria: * Diagnosis of MDS confirmed within 6 weeks prior to Screening according to WHO criteria or French-American-British (FAB) classification. * MDS classified as follows, according to WHO criteria and FAB classification: * RAEB-1 (5% to 9% BM blasts) * RAEB-2 (10% to 19% BM bla...
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Rigosertib is an investigational small molecule being studied in several cancers, including myelodysplastic syndrome, acute myelocytic leukemia, non-small cell lung cancer, head and neck neoplasms, head and neck squamous cell carcinoma, and advanced cancer. It has been tested both as a single agent and in combination with other therapies such as nivolumab and chemoradiotherapy.
Rigosertib is being developed by Traws Pharma, Inc., which trades under the ticker TRAW. The company is the sponsor behind the clinical program evaluating the drug across hematologic and solid tumor indications.
Rigosertib is in Phase 1 development. Its clinical program has included a Phase 3 study in myelodysplastic syndrome, along with Phase 1 and early Phase 1 trials in non-small cell lung cancer, head and neck cancer, and epidermolysis bullosa associated squamous cell carcinoma. All four listed trials are completed.
Rigosertib has been evaluated in four completed trials: NCT04263090 in KRAS-positive non-small cell lung cancer with nivolumab, NCT04177498 in recessive dystrophic epidermolysis bullosa associated squamous cell carcinoma, NCT02107235 in head and neck cancer with platinum-based chemoradiotherapy, and NCT01928537 in myelodysplastic syndrome with excess blasts.
Yes. Rigosertib sodium and oral rigosertib are alternative names for rigosertib. Rigosertib sodium refers to the salt form of the compound, while oral rigosertib describes the orally administered version of the drug. All of these names refer to the same investigational agent.
Rigosertib is not approved and remains an investigational agent in clinical development. Its trials, including a Phase 3 study in myelodysplastic syndrome and Phase 1 studies in solid tumors, have been completed, but the drug is still being evaluated and has not received regulatory approval.