Oncology - CHMP Minutes for the Meeting on 27-30 March 2023

Minutes from the EMA’s Committee for Medicinal Products for Human Use (CHMP) meeting on 27-30 March 2023 released on the 19^th of May 2023. Items of interest listed below:

Update on on-going initial applications for Centralised procedure

Trastuzumab

• Indication: treatment of metastatic and early breast cancer and metastatic gastric cancer (MGC)
• The CHMP agreed to the request by the applicant for an extension to the clock stop to respond to the list of outstanding issues adopted in December 2022.

Paclitaxel

• Indication: treatment of metastatic breast cancer
• The CHMP agreed to the request by the applicant for an extension to the clock stop to respond to the list of outstanding issues adopted in October 2022.

Extension of marketing authorization according to Annex I of Commission Regulation (EC) No 1234/2008; Day 120 List of question

Tecentriq – atezolizumab – Roche Registration GmbH

• “Extension application to introduce a new pharmaceutical form (solution for injection) associated with a new strength (1875 mg) and new route of administration(subcutaneous use). The RMP (version 24.0) is updated in accordance.”
• The Committee discussed the issues identified in this application, relating to quality and clinical aspects. The Committee adopted the CHMP recommendation and scientific discussion together with the list of questions.

Type II variations – variation of therapeutic indication procedure according to Commission Regulation  (EC) No 1234/2008; Opinions or Requests for supplementary information

Enhertu – trastuzumab deruxtecan – Daiichi Sankyo Europe GmbH

• “Extension of indication to include the indication treatment of non-small cell lung cancer for Enhertu (trastuzumab deruxtecan), based on results from study DS8201-A-U204 (DESTINY-Lung01) and study DS8201-A-U206 (DESTINY-Lung02). Study DESTINY-Lung01 is a phase 2, multicentre, open-label, 2-cohort study of trastuzumab deruxtecan (DS-8201a), an anti-HER2 antibody drug conjugate (ADC), for HER2-over-expressing or -mutated, unresectable and/or metastatic non-small cell lung cancer (NSCLC) conducted at sites in Japan, the United States and Europe. Study DESTINY-Lung02 is an ongoing phase 2, multicentre, obinutuzumab study to evaluate the safety and efficacy of trastuzumab deruxtecan in subjects with HER2-mutated metastatic non-small cell lung cancer, conducted in North America, Europe and Asia-Pacific. As a consequence, sections 4.1, 4.2, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 2.2 of the RMP has also been submitted.”
• The Committee discussed the issues identified in this application, relating to clinical aspects. The Committee adopted a request for supplementary information with a specific timetable.

Imfinzi - durvalumab - AstraZeneca AB

• “Extension of indication to include Imfinzi as treatment of adults with unresectable hepatocellular carcinoma (uHCC), based on final results from study D419CC00002 (HIMALAYA); this was a randomized, open-label, multi-center phase III study of durvalumab and tremelimumab as first-line treatment in patients with unresectable hepatocellular carcinoma (HIMALAYA). As a consequence, sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 9, Succession 1 of the RMP has also been submitted. In addition, the PI is brought in line with the latest QRD template version 10.3.”
• The Committee discussed the issues identified in this application, relating to clinical aspects. The Committee adopted a request for supplementary information with a specific timetable

CHMP assessed procedures scope: Non-Clinical and Clinical aspects

Lenvima - lenvatinib - Eisai GmbH,

• “Update of section 5.1 of the SmPC in order to update the efficacy information of "Endometrial carcinoma" based on the final OS analysis data for the overall population as well as for MMR subgroups from study E7080-G000-309 / KEYNOTE-775. This is a Multicenter, Open-label, Randomized, Phase III study to compare the efficacy and safety of lenvatinib in combination with pembrolizumab versus treatment of physician’s choice in participants with advanced endometrial cancer. In addition, the MAH took the opportunity to implement editorial changes in the SmPC.”
• Positive Opinion adopted by consensus on 09.03.2023.

Lynparza - olaparib - AstraZeneca AB

• “Submission of the final report from study AME02164. This is a Genetic Toxicity Evaluation using a Bacterial Reverse Mutation Test with Salmonella typhimurium LT2 Strains TA1535, TA1537, TA98 and TA100, and Escherichia coli WP2 Strain uvrA/pKM101.”
• Request for Supplementary Information adopted on 30.03.2023 with a specific timetable.

CHMP-PRAC assessed procedures

Padcev - enfortumab vedotin - Astellas Pharma Europe B.V.,

• “Update of sections 4.2, 4.4 and 4.8 of the SmPC in order to introduce new posology recommendations in case of pneumonitis/interstitial lung disease (ILD), add Positive Opinion adopted by consensus on 30.03.2023. A new warning on ‘pneumonitis/ILD’ and add it to the list of adverse drug reactions (ADRs) with frequency not known. The Package Leaflet is updated accordingly. The RMP version 2.0 has also been submitted. In addition, the MAH took the opportunity to introduce minor editorial changes to the PI.”
• Opinion adopted on 30.03.2023.

TUKYSA - tucatinib - Seagen B.V.,

• “Submission of the final report from study SGNTUC-017 (MOUNTAINEER) listed as a category 3 study in the RMP. This is a Phase 2, open label study of tucatinib combined with trastuzumab in patients with HER2+ metastatic colorectal cancer. Primary objective is to determine the antitumor activity of tucatinib given in combination with trastuzumab. The RMP version 1.1 is approved.”
• Positive Opinion adopted by consensus on 16.03.2023.

Type II Variations scope of the Variations: Extension of indication

Keytruda - pembrolizumab

Merck Sharp & Dohme B.V.,

• “Extension of indication to include in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as monotherapy as adjuvant, treatment of resectable stage II, IIIA, or IIIB (T3 4N2) non-small cell lung carcinoma in adults for Keytruda based on study KEYNOTE-671, a phase III, randomized, double-blind trial of platinum doublet chemotherapy +/- pembrolizumab as neoadjuvant/adjuvant therapy for participants with resectable stage II, IIIA, and resectable IIIB (T3-4N2) non-small cell lung cancer. As a consequence, sections 4.1, 4.2 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 41.1 of the RMP has also been submitted.”
• “Extension of indication to include in combination with chemotherapy the first-line treatment of locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma in adults based on study KEYNOTE-859, a randomized, double-blind phase 3 trial, evaluating KEYTRUDA in combination with chemotherapy compared to placebo in combination with chemotherapy for the first-line treatment of patients with HER2-negative locally advanced uresectable or metastatic gastric or GEJ adenocarcinoma. As a consequence, sections 4.1 and 5.1 of the SmPC are updated. The Package Leaflet and Annex II are updated in accordance. Version 42.1 of the RMP has also been submitted.”

CHMP assessed procedures scope: Non-Clinical and Clinical aspects

Keytruda - pembrolizumab

Merck Sharp & Dohme B.V.,

• “Update of section 5.1 of the SmPC in order to provide the final OS data (including analyses/KM plots from favourable prognosis subgroups) following the assessment of procedure II/0104, based on results from study E7080-G000-307/KEYNOTE 581 (REC); A Multicenter, Open-label, Randomized, Phase 3 Trial to Compare the Efficacy and Safety of Lenvatinib in Combination with Everolimus or Pembrolizumab Versus Sunitinib Alone in FirstLine Treatment of Subjects with Advanced Renal Cell Carcinoma (CLEAR).”

Kisplyx - lenvatinib

Eisai GmbH,

• “Update of section 5.1 of the SmPC in order to update efficacy information in first-line treatment of patients with renal cell carcinoma (in combination with pembrolizumab), based on the OS final analysis for the overall population from study E7080-G000-307/KEYNOTE 581; this is a multicenter, randomized, open-label, phase 3 study comparing the efficacy and safety of lenvatinib in combination with either pembrolizumab or everolimus versus sunitinib alone in first-line treatment of subjects with advanced renal cell carcinoma (RCC).