CHMP Minutes for November 2022 - Oncology

Minutes from the EMA’s Committee for Medicinal Products for Human Use (CHMP) meeting on 7-10 of November 2022 were  released on the 18th of January 2023. Items of interest listed below: 

Oral Explanations 

Post-authorisation procedure oral explanations 

Enhertu (trastuzumab deruxtecan) - Daiichi Sankyo Europe GmbH 

• Request for 1 year of market protection for a new indication (Article 14(11) of Regulation (EC) 726/2004) 

• Extension of indication to include monotherapy treatment of adult patients with advanced HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen for Enhertu based on final results from studies DS8201-A-U205 (DESTINY Gastric02) and DS8201 A J202 (DESTINY Gastric01); as a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1, and 5.2 of the SmPC are updated. The Annex II and Package Leaflet are updated in accordance. In addition, changes regarding the dosing recommendation for corticosteroid treatment and the protection of the infusion bag from light have been introduced. Version 3.0 of the RMP has also been submitted. 

• The CHMP agreed that an oral explanation was not needed at this time. 

Initial applications 

Initial applications; List of outstanding issues (Day 180; Day 120 for procedures with accelerated assessment timetable) 

Tremelimumab - AstraZeneca AB (Orphan) 

• Indication: For use in combination with durvalumab for the treatment of adults with unresectable hepatocellular carcinoma 
• The Committee was reminded of the status of this application and its remaining outstanding issues and adopted a list of outstanding issues with a specific timetable. 

Initial applications; List of questions (Day 120; Day 90 for procedures with accelerated assessment timetable) 

Degarelix acetate 

• Indication: treatment of prostate cancer 
• The Committee discussed the issues identified in this application and adopted the CHMP recommendation and scientific discussion together with the list of questions. 

Trastuzumab duocarmazine  

• treatment of HER2 (Human Epidermal Growth Factor Receptor 2)-positive metastatic breast cancer. 
• The Committee discussed the issues identified in this application and adopted the CHMP recommendation and scientific discussion together with the list of questions. 

Withdrawals of initial marketing authorisation application 

Febseltiq (infigratinib) - Helsinn Birex Pharmaceuticals Limited (Orphan) 

• Indication: treatme nt of cholangiocarcinoma 
• New active substance (Article 8(3) of Directive No 2001/83/EC) 

• The CHMP noted the withdrawal of the marketing authorisation application 

Type II variations - variation of therapeutic indication procedure 

Enhertu (trastuzumab deruxtecan) - Daiichi Sankyo Europe GmbH 

• Extension of indication to include monotherapy treatment of adult patients with advanced HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen for Enhertu based on final results from studies DS8201-A-U205 (DESTINY Gastric02) and DS8201 A J202 (DESTINY Gastric01); as a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated. The Annex II and Package Leaflet are updated in accordance. In addition, changes regarding the dosing recommendation for corticosteroid treatment and the protection of the infusion bag from light have been introduced. Version 3.0 of the RMP has also been submitted. 
• The CHMP agreed that an oral explanation was not needed at this time. 
• The Committee confirmed that all issues previously identified in this application had been addressed and adopted a positive opinion by consensus together with the CHMP Assessment Report and translation timetable. 

Iclusig (ponatinib) - Incyte Biosciences Distribution B.V. (Orphan) 

• Extension of indication to include treatment of newly diagnosed adult patients with Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL), either with Iclusig (ponatinib) in combination with chemotherapy, or with Iclusig (ponatinib) monotherapy after corticosteroid induction in patients not eligible to receive chemotherapy-based regimens, based on final results from studies AP24534-11-001 and INCB 84344-201. As a consequence, sections 4.1, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 22 of the RMP has also been submitted. 
• The Committee discussed the issues identified in this application, relating to clinical aspects and adopted a request for supplementary information with a specific timetable. 

Imfinzi (durvalumab) - AstraZeneca AB 

• Extension of indication to include Imfinzi in combination with tremelimumab for the 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. As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. In addition, the MAH took the opportunity to implement minor editorial changes in the SmPC and Package Leaflet. Version 6.1 of the RMP has also been submitted. 
• The Committee discussed the issues identified in this application, relating to clinical aspects. 
• The Committee adopted a 2nd request for a supplementary information with a specific timetable 

Imfinzi (durvalumab) - AstraZeneca AB 

• Extension of indication to include Imfinzi in combination with chemotherapy for the treatment of adults with locally advanced or metastatic biliary tract cancer (BTC), based on the second interim analysis from the ongoing pivotal study D933AC00001 (TOPAZ-1); a phase III randomized, double-blind, placebo-controlled, multi-regional, international study conducted to assess the efficacy and safety of durvalumab in combination with the current standard of care Gemcitabine/Cisplatin for the first-line treatment of patients with locally advanced or metastatic BTC. As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC have been updated and the package leaflet has been updated accordingly. Version 7.1 of the RMP has also been submitted. 
• The Committee confirmed that all issues previously identified in this application had been addressed and adopted a positive opinion by consensus together with the CHMP Assessment Report and translation timetable. 
• The CHMP also adopted the similarity assessment report. 

Lynparza (Olaparib) - AstraZeneca AB 

• Extension of indication to include treatment of adults with metastatic castration resistant prostate cancer (mCRPC), with Lynparza in combination with abiraterone and prednisone or prednisolone, based on the results of the pivotal Phase III study PROpel (D081SC00001) and supportive evidence from study 8 (D081DC00008). PROpel is a Phase III, randomised, double-blind, placebo-controlled, multicentre study evaluating olaparib vs placebo in combination with abiraterone as first line treatment for men with mCRPC. Consequently, sections 4.1, 4.2, 4.4, 4.8 and 5.1 of the SmPC for Lynparza tablets are being updated. In addition, sections 4.4 and 4.8 of the SmPC for Lynparza hard capsules are revised based on the updated safety data analysis. The Package Leaflet is updated accordingly. The RMP version 24 has also been submitted. 
• The Committee confirmed that all issues previously identified in this application had been addressed and adopted a positive opinion by consensus together with the CHMP Assessment Report and translation timetable. 

Pre-Submission issues  

talquetamab - Janssen-Cilag International N.V. (Orphan/PRIME) 

• Indication: indicated for the treatment of adult patients with relapsed or refractory multiple myeloma, who have previously received at least 3 prior therapies, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody. 

• The CHMP agreed to the request for accelerated assessment and adopted the briefing note and Rapporteurs’ recommendation on the Request for Accelerated Assessment. 

Post-authroisation issues 

Zejula (niraparib) - GlaxoSmithKline (Ireland) Limited 

• Update of sections 4.4 and 4.8 of the SmPC in order to amend an existing warning and add MDS/AML to the list of adverse drug reactions (ADRs) with frequency common and update of section 5.1 based on final results from NOVA study (213356); this is a Phase 3 Randomized Double-Blind Trial of Maintenance with Niraparib Versus Placebo in Patients with Platinum Sensitive Ovarian Cancer. In addition, the MAH also took this opportunity to update sections 4.4 and 4.6 to update information on contraception based on EMA and CTFG recommendations. The Package Leaflet is updated accordingly. The RMP version 6 has also been submitted. 
• The CHMP agreed on the need to consult a SAG and adopted a list of questions to this group. 

Gavreto (pralsetinib) - Roche Registration GmbH 

• Extension of indication to include monotherapy treatment of adult and paediatric patients 12 years of age and older with locally advanced or metastatic RET-mutant medullary thyroid cancer for Gavreto; based on the efficacy and safety data obtained from the pivotal study BO42863 (ARROW). As a consequence, sections 4.1, 4.2, 4.4, 4.5, 4.8, 5.1, 5.2 and 5.3 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 1.1 of the RMP has also been submitted. Furthermore, some minor changes to the PI have been implemented in line with the latest Anticancer Guidelines Recommendations. Extension of indication to include monotherapy treatment of adult and paediatric patients 12 years of age and older with locally advanced or metastatic RET fusion-positive thyroid cancer for Gavreto; based on the efficacy and safety data obtained from the pivotal study BO42863 (ARROW). As a consequence, sections 4.1, 4.2, 4.4, 4.5, 4.8, 5.1, 5.2 and 5.3 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 1.1 of the RMP has also been submitted. 
• Request for 1 year of market protection for a new indication. 
• The CHMP noted the withdrawal of the application of extension of indication. 

ANNEX 

POST-AUTHORISATION PROCEDURES OUTCOMES 

Atriance (nelarabine) - Novartis Europharm Limited 

• Positive Opinion adopted by consensus together with the CHMP assessment report. 
• The Marketing Authorisation remains under exceptional circumstances. 

Fulvestrant Mylan (fulvestrant) - Mylan Pharmaceuticals Limited 

• Positive Opinion adopted by consensus together with the CHMP assessment report and translation timetable. 

• The CHMP was of the opinion that the renewal of the marketing authorisation can be granted with unlimited validity. 

KANJINTI (trastuzumab) - Amgen Europe B.V. 

• Request for supplementary information adopted with a specific timetable. 

POST-AUTHORISATION PHARMACOVIGILANCE OUTCOMES 

• Imfinzi (durvalumab) 

• Signal of myelitis transverse 

• PRAC recommendation on a variation, The CHMP adopted the recommendation. 

• Vandetanib; Caprelsa (vandetanib) - Genzyme Europe BV 

• The CHMP, having considered in accordance with Article 28 of Regulation (EC) No 726/2004 the PSUR on the basis of the PRAC recommendation and the PRAC assessment report as appended recommends by consensus the variation to the terms of the marketing authorisation(s) for the above mentioned medicinal product(s), concerning the following change(s): Update of sections 4.4 and 4.8 of the SmPC to amend the warning/precaution regarding “Skin reactions” and to add the adverse reaction TEN with a frequency “not known”. The Package leaflet is updated accordingly. 

EPARs / WPARs 

Pemetrexed Baxter (pemetrexed) - Baxter Holding B.V. 

• Indication: treatment of malignant pleural mesothelioma and non-small cell lung cancer. 
• For information only. Comments can be sent to the PL in case necessary. 

Plerixafor Accord (plerixafor) - Accord Healthcare S.L.U. 

• Indication: treatment of lymphoma and multiple myeloma 
• For information only. Comments can be sent to the PL in case necessary. 

Pluvicto (lutetium (177Lu) vipivotide Tetraxetan) - Novartis Europharm Limited 

• Indication: treatment ofprostate-specific membrane antigen (PSMA)- positive metastatic castration-resistant prostate cancer. 
• For information only. Comments can be sent to the PL in case necessary. 

TYPE II VARIATION, WORKSHARING PROCEDURE OUTCOMES 

Imfinzi (durvalumab) -AstraZeneca AB 

• Positive Opinion adopted by consensus on 10.11.2022. 

SARCLISA (isatuximab) - sanofi-aventis groupe 

• Request for supplementary information adopted with a specific timetable. 

Xofigo (radium-223) - Bayer AG  

• Request for supplementary information adopted with a specific timetable. 

Blitzima, Truxima - Celltrion Healthcare Hungary Kft 

• Positive Opinion adopted by consensus on 20.10.2022. 

Alecensa (alectinib) - Roche Registration GmbH 

• Submission of the final report from study JO28928 (J-ALEX) a Randomized Phase III Open-Label Study Comparing the Efficacy and Safety of Crizotinib and CH5424802 in ALKPositive Advanced or Recurrent Non-Small Cell Lung Cancer. 

• Positive Opinion adopted by consensus on 27.10.2022. 

Darzalex (daratumumab) -Janssen-Cilag International N.V. (Orphan)  

• Update of section 4.8 of the SmPC in order to add COVID-19 to the list of adverse drug reactions (ADRs) with frequency uncommon, based on a pooled dataset from the following interventional studies 4767414MMY2004, 54767414MMY3003, 54767414MMY3006, 54767414MMY3008, and 54767414MMY3013. The Package Leaflet is updated accordingly. 
• Request for supplementary information adopted with a specific timetable. 

Nerlynx (neratinib) - Pierre Fabre Medicament 

• Update of section 5.2 of the SmPC in order to add information on distribution and on the effect of neratinib on CYP substrates based on non-clinical studies XT218036 and 20325317; study XT218036 was designed to evaluate neratinib as a substrate of the human transporters OATP1B1 and OATP1B3 and study 20325317 objective was to determine the inactivation kinetic constants (kinact and KI) of Neratinib and M6 for the human cytochrome P450 (CYP) isoenzymes 2B6 and 3A4 using pooled human liver microsomes (HLM). In addition, the MAH is taking this opportunity to introduce editorial changes. 
• Positive Opinion adopted by consensus on 10.11.2022. 

Piqray (alpelisib) - Novartis Europharm Limited 

• Update of the SmPC sections 4.6 and 5.3 in order to add fertility data based on studies 2070119 “BYL719: Oral (Gavage) Study of Fertility in the Male Rat” and 2070120 “BYL719: Oral (Gavage) Study of Fertility and Early Embryonic Development in the Female Rat”. 
• Positive Opinion adopted by consensus on 20.10.2022. 

Retsevmo (selpercatinib) - Eli Lilly Nederland B.V 

• Update of sections 4.5 and 5.2 of the SmPC in order to reflect the final results from the drug-drug interaction (DDI) study J2G-MCJZJV; this is a phase 1, single-center, openlabel, DDI study to investigate the effect of selpercatinib on the pharmacokinetic profiles of dabigatran, a P-glycoprotein (P-gp) substrate, in healthy volunteers. The Package Leaflet is updated accordingly. 
• Positive Opinion adopted by consensus on 10.11.2022. 

Venclyxto (venetoclax) - AbbVie Deutschland GmbH & Co. KG 

• Update of section 5.1 of the SmPC in order to update data supporting the efficacy of the combined regimen of obinutuzumab and venetoclax (VEN+G; also known as GDC-0199 or ABT-199) versus obinutuzumab plus chlorambucil (GClb) in previously untreated CLL patients based on final results from study BO25323/CLL14; this is a prospective, open-label, multicenter randomized phase 3 trial to compare the efficacy and safety of a combined regimen of obinutuzumab and venetoclax (GDC-0199/ABT-199) versus obinutuzumab and chlorambucil in previously untreated patients with CLL and coexisting medical conditions. In addition, the MAH took the opportunity to introduce minor editorial changes to the PI. 
• Positive Opinion adopted by consensus on 20.10.2022. 

Imnovid (pomalidomide) - Bristol-Myers Squibb Pharma EEIG (Orphan) 

• Update of section 4.4 of the SmPC, Annex IID and Article 127a and the tools/documents included in the Educational Healthcare Professional Kit, in order to harmonise the terminology utilised in the RMP and PI documents relating to the safety concern of teratogenicity and its risk minimization measure of the Pregnancy Prevention Plan across the 3 IMiDs. These proposed changes will only have a limited impact on the National Competent Authority (NCA)-approved content/text of the educational materials, and the key messages to the HCP and patients. Furthermore, the regulatory obligations regarding the PPP will not be impacted. The updated RMP version 16 was provided. 

• Request for supplementary information adopted with a specific timetable. 

Revlimid (lenalidomide) - Bristol-Myers Squibb Pharma EEIG 

• Update of section 4.4 of the SmPC, Annex IID and Article 127a and the tools/documents included in the Educational Healthcare Professional Kit, in order to harmonise the terminology utilised in the RMP and PI documents relating to the safety concern of teratogenicity and its risk minimization measure of the Pregnancy Prevention Plan across the 3 IMiDs. These proposed changes will only have a limited impact on the National Competent Authority (NCA)-approved content/text of the educational materials, and the key messages to the HCP and patients. Furthermore, the regulatory obligations regarding the PPP will not be impacted. The MAH is also taking the opportunity to update the RMP with PASS Protocol milestones. The updated RMP version 38 was provided. 
• Request for supplementary information adopted with a specific timetable. 

Thalidomide BMS (thalidomide) - Bristol-Myers Squibb Pharma EEIG 

• Update of section 4.4 of the SmPC, Annex IID and Article 127a and the tools/documents included in the Educational Request for supplementary information adopted with a specific timetable. Healthcare Professional Kit, in order to harmonise the terminology utilised in the RMP and PI documents relating to the safety concern of teratogenicity and its risk minimization measure of the Pregnancy Prevention Plan across the 3 IMiDs. These proposed changes will only have a limited impact on the National Competent Authority (NCA)-approved content/text of the educational materials, and the key messages to the HCP and patients. Furthermore, the regulatory obligations regarding the PPP will not be impacted. The MAH is also taking the opportunity to update the RMP with PASS Protocol milestones, and to make some editorial changes in the labelling. The updated RMP version 20 was provided. 
• Request for Supplementary Information adopted on 27.10.2022. 

OPDIVO, Yervoy - Bristol-Myers Squibb Pharma EEIG 

• Update of section 4.8 of the SmPC in alignment with the recommendations made by the CHMP to revise the pooling approach used to describe irARs and tabulated summaries of ADRs following II/0096. Individual study data included within this application has been previously reviewed by the CHMP. The updated Opdivo RMP version 29.0 and Yervoy RMP version 37.0 have also been submitted. The MAH took the opportunity to introduce editorial changes.  The Package Leaflet was updated accordingly.” 
• Positive Opinion adopted by consensus on 27.10.2022. 

Unclassified procedures and worksharing procedures of type I variations 

Herceptin, MabThera - Roche Registration GmbH 

• Positive Opinion adopted by consensus on 10.11.2022. 

START OF THE PROCEDURES 

Eribulin  

• Indication: treatment of breast cancer and liposarcoma 

Epcoritamab (Orphan) - AbbVie Deutschland GmbH & Co. KG 

• Indication: treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). 

Niraparib / abiraterone acetate 

• Indication: treatment of adult patients with prostate cancer 

• List of Questions adopted on 15.09.2022. 

Trastuzumab  

• Indication: treatment of metastatic and early breast cancer and metastatic gastric cancer (MGC) 
• List of Questions adopted on 19.05.2022. 

Ivosidenib - Les Laboratoires Servier (Orphan) 

• Indication: treatment of acute myeloid leukaemia and treatment of metastatic cholangiocarcinoma. 
• List of Questions adopted on 21.07.2022. 

Ivosidenib - Les Laboratoires Servier (Orphan) 

• treatment of acute myeloid leukaemia 
• List of Questions adopted on 21.07.2022. 

BLINCYTO (blinatumomab) -Amgen Europe B.V. (Orphan)  

JEMPERLI (dostarlimab) - GlaxoSmithKline (Ireland) Limited 

Nerlynx (neratinib) - Pierre Fabre Medicament 

Trazimera (trastuzumab) - Pfizer Europe MA EEIG 

Padcev (enfortumab vedotin) - Astellas Pharma Europe B.V 

Zaltrap (aflibercept) - sanofi-aventis groupe 

Calquence (acalabrutinib) - AstraZeneca AB 

• Update of section 5.1 of the SmPC based on the interim report of study ACE-CL-007; a randomized, multicenter, open-Label, 3-arm phase 3 study of obinutuzumab in combination with chlorambucil, ACP-196 in combination with obinutuzumab, and ACP-196 monotherapy in subjects with previously untreated chronic lymphocytic leukemia. 

Imfinzi (durvalumab) - AstraZeneca AB 

• Update of section 4.2 of the SmPC in order to update the recommendation for dose modification for ‘other immune-mediated adverse reactions’ as well as immune-mediated encephalitis, meningitis, Guillain-Barré syndrome and myasthenia gravis based on the National Comprehensive Cancer Network (NCCN) guideline recommendations (2022). 

Myocet liposomal (doxorubicin hydrochloride) - Teva B.V 

• Update of section 4.6 of the SmPC, upon request by PRAC following the assessment of to align the wording with the published CHMP SWP advice on the duration of contraception in female patients after cessation of treatment with genotoxic drug. The Package Leaflet has been updated accordingly. 

SARCLISA (isatuximab) - sanofi-aventis groupe 

• C.I.4: Update of sections 4.5, 5.1 and 5.2 of the SmPC in order to update the efficacy and pharmacokinetic data based on final progression-free survival (PFS) efficacy results from IKEMA study (EFC15246) and to introduce the Sebia Hydrashift assay, a validated assay to determine the complete response rate. IKEMA study (EFC15246) is a phase 3 randomized, open label, multicenter study assessing the clinical benefit of isatuximab combined with carfilzomib (Kyprolis) and dexamethasone versus carfilzomib with dexamethasone in patients with relapsed and/or refractory multiple myeloma previously treated with 1 to 3 prior lines. A.6: Update of section 5.1 of the SmPC in order to update the ATC code following amendment by WHO. 

Rubraca (rucaparib) - Clovis Oncology Ireland Limited 

• Update of sections 4.8 and 5.1 of the SmPC in order to update the efficacy and safety information and the list of adverse drug reactions (ADRs) based on the final results from study CO-338-014 (ARIEL 3) listed as a category 1 PAES in the Annex II; this is a phase 3, multicenter, randomized, double-blind, placebo-controlled study of rucaparib as switch maintenance following platinum-based chemotherapy in patients with platinumsensitive, high grade serous or endometrioid epithelial ovarian, primary peritoneal or fallopian tube cancer. The Package Leaflet is updated accordingly. The RMP version 6.4 has also been submitted. In addition, the MAH took the opportunity to introduce minor editorial changes to the PI. 

Breyanzi (lisocabtagene maraleucel / lisocabtagene maraleuce) - Bristol-Myers Squibb Pharma EEIG (ATMP) 

Herceptin, MabThera - Roche Registration GmbH 

Document Source: CHMP Minutes 7-10 November 2022