Ipsen: ESMO 2021: Cabometyx® Demonstrates Sustained 78% Reduction in Risk of Disease Progression or Death in People Living With Uncommon Form of Thyroid Cancer
Ipsen announced the validation of its submission for an indication extension of Cabometyx (cabozantinib) by the
- Cabometyx showed a 78% reduction in the risk of disease progression or death in the COSMIC-311 trial (HR: 0.22, p<0.0001).
- Validation of the submission by the
European Medicines Agency for an extension of indication established Cabometyx's potential utility.
- Discontinuation rates due to treatment-emergent adverse events (TEAEs) were 8.8% for Cabometyx versus 0% for placebo.
- Grade 3/4 TEAEs occurred in 62% of patients receiving Cabometyx compared to 28% for placebo.
-
Ipsen’s submission for extension of indication for Cabometyx® (cabozantinib) based on data from the COSMIC-311 trial received validation from the
European Medicines Agency inAugust 2021 -
Separate follow-up data presented at the
European Society for Medical Oncology Congress 2021 includes cohort 6 of the Phase Ib COSMIC-021 trial and the Phase III CheckMate -9ER trial, reinforcing the broad utility potential of Cabometyx across indications2-4
Disclaimer: Intended for international media and investor audiences only
With a median follow-up of 10.1 months, Cabometyx continued to demonstrate superior median progression-free survival (mPFS) with a reduction in the risk of disease progression or death of
Efficacy and safety data from the COSMIC-311 interim analysis formed the basis of a type II variation submission to the
The safety profile identified in the COSMIC-311 trial was consistent with that previously observed for cabozantinib and adverse events (AEs) were managed with dose modifications. The discontinuation rate due to treatment-emergent AEs (TEAEs) was
Additional data to be presented at ESMO featuring Cabometyx include new results from cohort 6 of the COSMIC-021 Phase Ib trial evaluating the combination of Cabometyx and atezolizumab in people living with previously treated metastatic castration-resistant prostate cancer (mCRPC) (Abstract LBA24).2 These additional analyses build on the interim data presented at ASCO 2020,7 with an expanded cohort 6 of 132 patients evaluated.2 With a median follow-up of 15.2 months, the primary endpoint of objective response rate (ORR) assessed by investigator per RECIST 1.1 (response evaluation criteria in solid tumours) was
Prof.
Further analyses from the landmark Phase III CheckMate -9ER trial investigating the combination of Cabometyx and nivolumab were are also being presented at ESMO, providing additional evidence to inform clinical decision-making in advanced renal cell carcinoma (RCC). New data demonstrated improved efficacy for Cabometyx and nivolumab regardless of prior nephrectomy status, when measured by PFS, ORR, CR and response durability outcomes, versus sunitinib (Abstract 663P).3 Additionally, a matching-adjusted indirect comparison analysis is being presented, demonstrating superior, statistically significant differences in health-related quality of life across all outcomes analysed in favour of Cabometyx and nivolumab versus the combination of axitinib and pembrolizumab (Abstract 668P).4
More information on these data can be found during the presentation sessions outlined below:
Title |
Date and time |
Cabozantinib in combination with atezolizumab in patients with metastatic castration-resistant prostate cancer (mCRPC): results of expanded cohort 6 of the COSMIC-021 Study |
Saturday 18 September
|
Cabozantinib Versus Placebo in Patients With Radioiodine-Refractory Differentiated Thyroid Cancer (DTC) Who Have Progressed After Prior VEGFR-Targeted Therapy: Updated Results From the Phase 3 COSMIC-311 Trial |
Monday 20 September
|
First-line nivolumab + cabozantinib (NIVO+CABO) vs sunitinib (SUN) in patients (pts) with advanced renal cell carcinoma (aRCC) in subgroups based on prior nephrectomy in the CheckMate 9ER trial |
Poster presentation – Available on-demand beginning |
Matching-adjusted indirect comparison (MAIC) of health-related quality of life (HRQoL) of nivolumab plus cabozantinib (N+C) vs pembrolizumab plus axitinib (P+A) in previously untreated advanced renal cell carcinoma (aRCC) |
Poster presentation – Available on-demand beginning |
About radioactive iodine-refractory differentiated thyroid cancer (RAI-R DTC)
In 2020, over 580,000 new cases of thyroid cancer were diagnosed worldwide.8 Thyroid cancer is the ninth most commonly occurring cancer globally and incidence is three times higher in women than in men, with the disease representing one in every 20 cancers diagnosed among women.7 While cancerous thyroid tumors include differentiated, medullary and anaplastic forms, differentiated thyroid tumors make up about 90 to
About the COSMIC-311 trial
COSMIC-311 is a multicenter, randomized, double-blind, placebo-controlled Phase III trial that enrolled 258 patients at 164 sites globally.6 Patients were randomized in a 2:1 ratio to receive either Cabometyx 60 mg or placebo once-daily.6 The primary endpoints were progression-free survival and objective response rate, evaluated by a blinded independent radiology committee. Additional endpoints include safety, overall survival and quality of life.2 More information about this trial is available at ClinicalTrials.gov.
About metastatic castration-resistant prostate cancer (mCRPC)
In 2020, over 1.4 million new cases of prostate cancer were diagnosed worldwide,13 making it the fourth most commonly occurring cancer globally.13 Prostate cancer that has spread beyond the prostate and does not respond to androgen-suppression therapies which reduce the levels of testosterone, a common treatment for prostate cancer, is known as mCRPC.14 Men diagnosed with mCRPC often have a poor prognosis, with an estimated survival of 1-2 years.15
About the COSMIC-021 trial
COSMIC-021 is a multicenter, Phase Ib, open-label trial that is divided into two parts: a dose-escalation phase and an expansion cohort phase. The dose-escalation phase was designed to enroll patients either with advanced renal cell carcinoma (RCC) with or without prior systemic therapy or with inoperable, locally advanced, metastatic or recurrent urothelial carcinoma (UC), (including renal, pelvis, ureter, urinary bladder and urethra) after prior platinum-based therapy. Ultimately, all 12 patients who enrolled in this stage of the trial were patients with advanced RCC. The dose-escalation phase of the study determined the optimal dose of cabozantinib to be 40 mg daily when given in combination with atezolizumab (1200 mg infusion once every 3 weeks).
In the expansion phase, the trial is enrolling 24 cohorts in 12 tumor types: RCC, urothelial carcinoma, non-small cell lung cancer, CRPC, hepatocellular carcinoma, triple-negative breast cancer, epithelial ovarian cancer, endometrial cancer, gastric or gastroesophageal junction adenocarcinoma, colorectal adenocarcinoma, head and neck cancer, and DTC.
Four of the cohorts are exploratory single agent cohorts. In UC, NSCLC, CRPC with cabozantinib as a single-agent, and in CRPC with single-agent atezolizumab.
Exelixis is the study sponsor of COSMIC-021. Both
About renal cell carcinoma (RCC)
There are over 400,000 new cases of kidney cancer diagnosed worldwide each year.16 Of these, RCC is the most common type of kidney cancer, accounting for approximately
About the CheckMate -9ER trial
CheckMate -9ER was an open-label, randomized, multi-national Phase III trial evaluating people living with previously untreated advanced or metastatic RCC. A total of 651 patients (
About Cabometyx (cabozantinib)
In the
The detailed recommendations for the use of Cabometyx are described in the Summary of Product Characteristics (EU SmPC) and in the
Ipsen has exclusive rights for the commercialization of Cabometyx outside the
About Ipsen
Ipsen is a global, mid-sized biopharmaceutical company focused on transformative medicines in Oncology, Rare Disease and Neuroscience; it also has a well-established consumer healthcare business. With total sales of over
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References
- Capdevila et al., ESMO 2021. Cabozantinib (C) versus placebo (P) in patients (pts) with radioiodine-refractory (RAIR) differentiated thyroid cancer (DTC) who have progressed after prior VEGFR-targeted therapy: updated results from the phase 3 COSMIC-311 trial and prespecified subgroup analyses based on prior VEGFR-targeted therapy
- Agarwal et al., ESMO 2021. Cabozantinib (C) in combination with atezolizumab (A) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): primary analysis of cohort 6 of the COSMIC-021 study
- Porta et al., ESMO 2021. First-line nivolumab + cabozantinib (NIVO+CABO) vs sunitinib (SUN) in patients (pts) with advanced renal cell carcinoma (aRCC) in subgroups based on prior nephrectomy in the CheckMate 9ER trial
- Porta et al., ESMO 2021. Matching-adjusted indirect comparison (MAIC) of health-related quality of life (HRQoL) of nivolumab plus cabozantinib (N+C) vs pembrolizumab plus axitinib (P+A) in previously untreated advanced renal cell carcinoma (aRCC)
- Brose et al., ASCO 2021. Cabozantinib versus placebo in patients with radioiodine-refractory differentiated thyroid cancer who have progressed after prior VEGFR-targeted therapy: results from the phase 3 COSMIC-311 trial.
- Brose et al., Cabozantinib for radioiodine-refractory differentiated thyroid cancer (COSMIC-311): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncology. 2021; 22:8. DOI: https://doi.org/10.1016/S1470-2045(21)00332-6
- Agarwal et al., ASCO 2020. Cabozantinib in combination with atezolizumab in patients with metastatic castration-resistant prostate cancer: Results of cohort 6 of the COSMIC-021 study.
- Sung. H et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal For Clinicians. doi: 10.3322/caac.21660.
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Cancer.Net. ASCO. Thyroid Cancer: Introduction. Last accessed:
September 2021 . Available at: https://www.cancer.net/cancer-types/thyroid-cancer/introduction - Chen D. et al. Innovative analysis of distant metastasis in differentiated thyroid cancer. Oncol Lett 19: 1985-1992, 2020. doi: 10.3892/ol.2020.11304.
- Worden F. Treatment strategies for radioactive iodine-refractory differentiated thyroid cancer. Ther Adv Med Oncol. 6:267–279. doi: 10.1177/1758834014548188.
- Fugazzola L. et al. 2019 European Thyroid Association Guidelines for the Treatment and Follow-Up of Advanced Radioiodine-Refractory Thyroid Cancer. Eur Thyroid J. 2019;8:227–245. doi: 10.1159/000502229.
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September 2021 . Available at: https://www.cancer.net/cancer-types/prostate-cancer/types-treatment - Moreira, D. M., et al. Predicting Time From Metastasis to Overall Survival in Castration-Resistant Prostate Cancer: Results From SEARCH. Clin Genitourin Cancer. 2017; 15: 60–66.e2.
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