Comparing Ivosidenib with Ivosidenib Recommended Combination Dose for locally advanced, unresectable or metastatic

Exclusion

• −Hepatitis B (clinical evaluation includes: presence of hepatitis B surface antigen \[HBsAg\] and/or anti-HBcAb with detectable hepatitis B virus \[HBV\] DNA ≥ 10 IU/mL)
• −Hepatitis C
• −Human immunodeficiency virus (clinical evaluation includes: positive HIV 1/2 antibodies) Note: Patients with a resolved or past HBV infection (i.e., presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) do not need to be excluded from the study. Patients positive for hepatitis C (HCV) antibody are eligible only if the polymerase chain reaction is negative for HCV RNA.
• −Received treatment for locally advanced, unresectable or metastatic disease with the following exceptions:
• −Treatment with up to one cycle of durvalumab plus gemcitabine/cisplatin treatment is permitted before study participation. Note: For the Safety Lead-In Phase, participants who received one prior cycle of durvalumab plus gemcitabine/cisplatin and required dose modifications for treatment-related toxicity are excluded.
• −Prior exposure to immune-mediated therapy, including, but not limited to, anti-PD-1or other anti-PD-L1, and anti-PD-L2, anti-CTLA-4 antibodies, excluding therapeutic anticancer vaccines.
• −Unresolved Grade ≥2 adverse eventsAdverse eventAny medical problem that happens during a study, whether or not the treatment caused it.Read more → from a previous anticancer therapy, with the exception of alopecia and vitiligo and the laboratory values listed in the inclusion criteriaInclusion criteriaThe things you must have or be for a study to consider you.Read more →.
• −Patients with Grade ≥2 neuropathy to be evaluated on a case-by-case basis after consultation with the medical monitor
• −Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with ivosidenib may be included only after consultation with the medical monitor
• −Participation in another interventional studyInterventional studyA study where participants are given something to see what happens.Read more → at the same time or within 14 days prior to the first study medication (triple combination treatment) administration. For patients having participated to another prior interventional study, the first dose of ivosidenib should occur after a period greater than or equal to 5 half-lives or 28 days, whichever is shorter of the last dose of the prior investigational product.
• −Active or prior documented autoimmune or inflammatory disorders including:
• −inflammatory bowel disease (e.g., colitis or Crohn's disease)
• −diverticulitis (with the exception of diverticulosis)
• −systemic lupus erythematosus
• −Sarcoidosis syndrome
• −Wegener syndrome (granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.)
• −Note: in cases with no active disease for ≥ 5 years, patients may be considered for inclusion if approved by the Medical Monitor. Participants with the following conditions are eligible for the study:
• −chronic skin condition that does not require systemic therapy
• −hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement therapy
• −unmedicated celiac disease that is controlled by diet
• −Have heart rate-corrected QT interval using Fridericia's formula (QTcF) of ≥ 450 msec or with other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome/sudden death, polymorphic ventricular arrhythmia). The SponsorSponsorThe organisation responsible for the study overall.Read more → should review participants with bundle branch block and prolonged QTcF for potential inclusion.
• −Have an active infection, including:
• −Tuberculosis (clinical evaluation includes: clinical history, physical examination and/or radiographic findings, and tuberculosis testing as per local practice)
• −Patients who developed recurrent disease \> 6 months after surgery with curative intent, and, if given, \> 6 months after the completion of adjuvant (chemotherapy and/or radiation).