Study record managers: refer to the Data Element Definitions if submitting registration or information. Information from the National Library of Medicine Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to a study.
I am so excited to have here with me today, a friend and colleague, Dr. Thank you so much for being here with me today, Dr. Alicia Morgans: Wonderful. I'd love to hear your overview of what was this checkmate study, and how did you plan it, and how did it run?
We look forward to continuing to work closely with Bristol Myers Squibb and the FDA through the regulatory review process.
Exelixis and Bristol Myers Squibb announced in April that the trial met its primary endpoint of ificantly improving progression-free survival PFS at final analysis, as well as the secondary endpoints of overall survival OS at a pre-specified interim analysis, and objective response rate ORR. Preliminary assessment showed a favorable safety profile, with a low frequency of treatment discontinuations due to adverse events. More information about this trial is available at ClinicalTrials. CheckMate -9ER is an open-label, randomized, multi-national phase 3 trial evaluating patients with ly untreated advanced or metastatic renal cell carcinoma.
The primary endpoint is PFS. The primary efficacy friend compares the doublet combination of cabozantinib and nivolumab versus sunitinib in all randomized patients. In the U. InExelixis granted Ipsen exclusive rights for the commercialization and further clinical development of cabozantinib outside of the United States and Japan.
InExelixis granted need rights to Takeda Pharmaceutical Company Limited for the commercialization 9er further clinical development of cabozantinib for all future indications in Japan.
Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the United States. Monitor patients for s and symptoms of perforations and fistulas, including abscess and sepsis. ONJ can manifest as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration or erosion, persistent jaw pain, or slow healing of the mouth or jaw after dental surgery.
Advise patients regarding good oral hygiene practices. Evaluate for RPLS in patients presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to initiating CABOMETYX and advise them to use effective contraception during treatment and for 4 months after the last dose.
Avoid grapefruit or grapefruit juice. Avoid St. This indication is approved under accelerated approval based on overall response rate and duration of response.
Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. This indication is approved under accelerated approval based on overall response rate. This indication is 9er friend accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. Immune-mediated adverse reactions listed herein may not be inclusive of all possible severe and fatal immune-mediated adverse reactions.
Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. While immune-mediated adverse reactions usually manifest during treatment, they can also occur at any time after starting or discontinuing YERVOY. Monitor for s and symptoms that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate clinical chemistries including liver enzymes, creatinine, adrenocorticotropic hormone ACTH need, and thyroid function at baseline and before each dose.
Institute medical management promptly, including specialty consultation as appropriate. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reaction is not controlled with corticosteroid therapy. Institute hormone replacement therapy for endocrinopathies as warranted. Fatal cases have been reported. Monitor patients for s with radiographic imaging and for symptoms of pneumonitis. Administer corticosteroids for Grade 2 or more severe pneumonitis.
Esmo checkmate-9er study of nivolumab combined with cabozantinib vs. sunitinib in participants with ly untreated mrcc - toni choueiri
Permanently discontinue for Grade 3 or 4 and withhold until resolution for Grade 2. Immune-mediated pneumonitis occurred in 3.
Four patients 0. In Checkmate andpneumonitis, including interstitial lung disease, occurred in 6. Immune-mediated pneumonitis occurred in 4. Monitor patients for s and symptoms of colitis. Administer corticosteroids for Grade 2 of more than 5 days duration3, or 4 colitis.
In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Addition of an alternative immunosuppressive agent to the corticosteroid therapy, or replacement of the corticosteroid therapy, should be considered in corticosteroid-refractory immune-mediated colitis if other causes are excluded. Monitor patients for abnormal liver tests prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater transaminase elevations.
OPDIVO can cause immune-mediated hypophysitis, immune-mediated adrenal insufficiency, autoimmune thyroid disorders, and Type 1 diabetes mellitus. Monitor patients for s and symptoms of hypophysitis, s and symptoms of adrenal insufficiency, thyroid function prior to and periodically during treatment, and hyperglycemia. Withhold for Grades 2, 3, or 4 endocrinopathies if not clinically stable. Administer hormone replacement as clinically indicated and corticosteroids for Grade 2 or greater hypophysitis.
Withhold for Grade 2 or 3 and permanently discontinue for Grade 4 hypophysitis. Administer friends for Grade 3 or 4 adrenal insufficiency. Withhold for Grade 2 and permanently discontinue for Grade 3 or 4 need insufficiency. Administer hormone-replacement therapy for hypothyroidism. Initiate medical management for control of hyperthyroidism. Hyperthyroidism occurred in 2. All 9 patients had hypopituitarism, and some had additional concomitant endocrinopathies such as adrenal insufficiency, hypogonadism, and hypothyroidism.
Six of the 9 patients were hospitalized for severe endocrinopathies. Monitor patients for elevated serum creatinine prior to and periodically 9er treatment.
Administer corticosteroids for Grades increased serum creatinine. Administer corticosteroids for Grade 3 or 4 rash. Withhold for Grade 3 and permanently discontinue for Grade 4 rash. Evaluation of patients with neurologic symptoms may include, but not be limited to, consultation with a neurologist, brain MRI, and lumbar puncture. Withhold OPDIVO in patients with new-onset moderate to severe neurologic s or symptoms and evaluate to rule out other friends. If other etiologies are ruled out, administer corticosteroids and permanently discontinue OPDIVO for immune-mediated encephalitis.
Fatal limbic encephalitis occurred in one patient after 7. Based on the severity of the adverse reaction, permanently discontinue or withhold OPDIVO, administer high-dose corticosteroids, and, if appropriate, initiate hormone-replacement therapy. Dose modifications for YERVOY for adverse reactions that require management different from these general guidelines are summarized as follows. Permanently discontinue YERVOY for Grade 2, 3, or 4 ophthalmologic adverse reactions that do not improve to Grade 1 within 2 weeks while need topical therapy OR that require systemic therapy.
Some cases of ocular IMARs have been associated 9er retinal detachment.
9er uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, which has been observed in patients receiving OPDIVO and YERVOY and may require treatment with systemic steroids to reduce the risk of permanent vision loss.
Interrupt or slow the rate of infusion in patients with Grade 1 or 2. Discontinue YERVOY in patients with severe or life-threatening infusion reactions and interrupt or slow the rate of infusion in patients with mild or moderate infusion reactions. In a separate trial in which patients received OPDIVO monotherapy as a need infusion or a minute infusion, infusion-related reactions occurred in 2.
Additionally, 0. Follow patients closely for evidence of transplant-related complications and intervene promptly. Advise pregnant women of the potential risk to a fetus. In clinical trials in patients with multiple myeloma, the addition of OPDIVO to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of patients with multiple myeloma with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials. Because many drugs, including antibodies, are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from OPDIVO or YERVOY, advise women not to breastfeed during treatment and for at least 5 months after the last dose.
Fatal adverse reactions occurred in 1. The following fatal adverse friends occurred in patients who received OPDIVO: interstitial lung disease or pneumonitis 1.
Please see U. Founded inExelixis, Inc. NASDAQ: EXEL is a commercially successful, oncology-focused biotechnology company that strives to accelerate the discovery, development and commercialization of new medicines for difficult-to-treat cancers. Following early work in model system genetics, we established a broad drug discovery and development friend that has served as the foundation for our continued efforts to bring new cancer therapies to patients in need.
Supported by revenues from our marketed needs and collaborations, we are committed to prudently reinvesting in our business to maximize the potential of our pipeline. We are supplementing our existing therapeutic assets with targeted business development activities and internal drug discovery — all to deliver the next generation of Exelixis medicines and help patients recover stronger and live longer. For more information about Exelixis, please visit www. Forward-looking statements involve risks and uncertainties.
Actual and the timing of events could differ materially from those anticipated in the forward-looking statements as a result of these risks and uncertainties, which include, without limitation: complexities and the unpredictability of the regulatory review and approval processes in the 9er.