• 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 in August 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

PARIS, FRANCE, 18 September 2021 – Ipsen (Euronext: IPN; ADR: IPSEY) today announced presentation of new analyses at the European Society for Medical Oncology (ESMO) Congress 2021 across different forms of cancer for people treated with Cabometyx® (cabozantinib). Of note, the final analysis of the pivotal Phase III COSMIC-311 trial (Abstract LBA67) will be presented, with Cabometyx demonstrating a clinically meaningful, sustained efficacy benefit versus placebo in people living with previously treated radioactive iodine-refractory differentiated thyroid cancer (RAI-R DTC).

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 78% versus placebo (hazard ratio [HR]: 0.22, 96% confidence interval [CI]: 0.15-0.32; p<0.0001).1 This final analysis is consistent with data from the interim analysis, presented at the American Society of Clinical Oncology (ASCO) Annual Meeting 2021 and published in The Lancet Oncology, (HR: 0.22; 96% CI: 0.13-0.36; p<0.0001).5,6 Further data from the final analysis also confirmed that superior efficacy with Cabometyx was maintained irrespective of previous vascular endothelial growth factor receptor (VEGFR)-targeted therapy.

Efficacy and safety data from the COSMIC-311 interim analysis formed the basis of a type II variation submission to the European Medicines Agency (EMA) for an extension of indication for Cabometyx in RAI-R DTC. On 14 August 2021, the EMA validated the type II variation, confirming the submission is complete and beginning its centralized review process.
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 8.8% for Cabometyx vs. 0% for placebo. Grade 3/4 TEAEs occurred in 62% of patients who received Cabometyx vs. 28% for placebo, with no treatment-related grade 5 events.

Steven Hildemann, M.D., Executive Vice President, Chief Medical Officer, Head of Global Medical Affairs and Global Patient Safety, Ipsen said “The therapeutic potential of Cabometyx as a key treatment option in our arsenal against a broad range of tumors is continuing to be realized. These final data from the COSMIC-311 trial are a strong example of how Cabometyx can make a tangible difference to the lives of people living with cancer and we look forward to receiving a decision from the EMA next year. We are committed to further evaluating the role Cabometyx may continue to play against difficult-to-treat cancers as we also look towards the results of the ongoing Phase III trials in non-small cell lung cancer (CONTACT-01) and metastatic castration-resistant prostate cancer (CONTACT-02).”

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 23%, with three patients demonstrating a complete response (CR).2

Prof. Dr. Gunhild von Amsberg, University Medical Center Hamburg-Eppendorf (UKE) and investigator in the CONTACT-02 trial, said “As a uro-oncologist, I am encouraged by the results presented at this year’s ESMO congress. For people living with advanced metastatic castration-resistant prostate cancer, the prognosis is often poor and the potential of new innovative therapies is critically important. Based on these clinically meaningful results of Cabometyx plus atezolizumab from cohort 6 of the COSMIC-021 trial, we now look forward to the results of the ongoing Phase III CONTACT-02.”

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:

References

1. 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
2. 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
3. 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 theCheckMate 9ER trial
4. 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)
5. 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.
6. 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
7. 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.

Attachment

• Ipsen-ESMO-2021-18-February-2021