As reported in OncLive, intravenously-administered rigosertib failed to meet the primary endpoint within the Phase 3 INSPIRE clinical trial. Ultimately, the trial sought to understand whether rigosertib could improve overall survival rate in patients with higher-risk myelodysplastic syndromes (HR-MDS). However, the trial determined that rigosertib provided no significant clinical benefit to patients.
INSPIRE Trial for Rigosertib
Rigosertib previously showed promise in a Phase 1/2 clinical trial. That showed that the drug benefited patients with acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML), and HR-MDS. Patients received either 140mg rigosertib 2x daily, 280mg 2x daily, or 840mg daily. Of the participants, 56% saw decreased bone marrow blasts. At least 5 patients were able to stop transfusions. Side effects included diarrhea, constipation, fatigue, pneumonia, nausea, pneumonia, neutropenia, thrombocytopenia, and back pain.
In the Phase 3 INSPIRE trial, researchers wanted to determine the safety, efficacy, and tolerability of rigosertib for patients with treatment-adverse HR-MDS. First, the trial enrolled 360 patients with MDS who were 82 years old or younger. To be eligible to participate, patients must have previously taken azacitidine or decitabine. Patients received 1800mg/24 hours rigosertib for the first 3 days of a 2-week treatment cycle for 8 cycles, then the first 3 weeks of a 4-week cycle. In comparison, researchers were determining the efficacy of a doctor’s therapeutic choice. Ultimately, the primary trial endpoint was overall survival rate.
However, the therapy was not effective in terms of increasing survival. Overall survival rate for participants taking rigosertib was 6.4 months. For those taking another option chosen by the doctor, the survival rate was 6.3 months. While the treatment was generally well-tolerated and non-toxic, there was no significant improvement on survival. As a result, it failed the primary endpoint.
Myelodysplastic Syndromes (MDS)
Myelodysplastic syndromes (MDS) are a group of progressive conditions which stop the bone marrow from producing enough healthy platelets, as well as red and white blood cells. Researchers aren’t sure exactly what causes MDS. However, potential causes include radiation, chemotherapy, chemical exposure, and genetic predisposition. There are five forms of MDS: refractory anemia, refractory anemia with sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia. In each case, blood cells either stay in the bone marrow or die early. They never mature.
In half of all cases, MDS progresses to acute myeloid leukemia (AML). However, some patients may still live long and happy lives. Disease progression varies. Often, MDS affects those over 60. It typically affects males more than females. Symptoms include:
- Low energy
- Frequent sinus, lung, skin, and urinary tract infections
- Pale skin
- Heart palpitations
- Difficulty breathing
- Neutropenia (low white blood cell count)
- Chest pain
- Thrombocytopenia (low platelet count)
- Easy bruising and bleeding
Learn more about MDS.