Rome, 19 June. (Adnkronos Health) – With 400 thousand new diagnoses estimated in 2023, over 18 thousand more cases than in 2020, cancer in Italy represents an emergency. According to experts, the worst is yet to come: between now and 2030 they predict that new diagnoses of malignant tumors will increase by 69%, with an increase in deaths by 72%.
“For over 30 years, J&J has contributed to meeting the unmet care needs of cancer patients and improving their life expectancy and quality. This is thanks to our desire to realize J&J’s mission: working for a future in which diseases are a memory of the past. Our pipeline – states Alessandra Baldini, medical director of Johnson & Johnson Innovative Medicine Italia – continues to grow and be enriched with increasingly advanced and increasingly personalized therapies, and this is made possible by our constant commitment to research and development of innovative drugs”. But not only that: “J&J’s commitment – adds Baldini – is also strengthened through numerous external collaborations, aimed at exploiting computational tools and artificial intelligence to produce innovative evidence, based on the observation and analysis of real data, which allow us to make cancer an increasingly manageable condition with cure prospects”.
In the onco-haematology area, the company has approved 14 drugs in just over 10 years, of which 8 are the founders of their class – reports a note – By 2030, 35 new requests for authorization are expected globally regulatory agencies, between new molecules or combinations and indication extensions. Of these, 15 will be in the field of blood cancers, 3 in prostate cancer, 3 in lung cancer, 4 in bladder cancer and over 5 in other areas, with an average of 2 new therapies available to patients per year. As evidence of its commitment to clinical research, J&J presented over 85 abstracts, including 20 presentations, on new clinical and real-world data at the latest congresses of the American Society of Clinical Oncology (Asco) and the European Hematology Association (Eha) 2024 -world in immunotherapies for solid and hematological tumors.
In the field of solid tumors – we read in the note – J&J is revolutionizing the standards of care for non-small cell lung cancer (NSCLC) with Egfr mutations thanks to amivantamab – a fully human, first-in-class bispecific antibody , for the recognition of mutated epidermal growth factor receptors (Egfr) and mesenchyme-epidermal transition (Met). During the Asco 2024 congress, data from the phase 3 Paloma III study were presented which evaluated the efficacy and pharmacokinetics of the subcutaneous (SC) formulation of amivantamab in combination with lazertinib compared to the combination administered intravenously (IV) in patients with advanced or metastatic Nsclc with Egfr receptor exon 19 deletion or L858R mutations, after progression with osimertinib and chemotherapy. The data showed that the subcutaneous formulation is associated with a significantly shorter administration time than the intravenous formulation, approximately 5 minutes versus 5 hours, decreasing infusion-related reactions by 5-fold, with pharmacokinetics and efficacy comparable to current intravenous administration. At a median follow-up of 7 months, amivantamab SC therapy also demonstrated increased duration of response (Dor) and progression-free survival (Pfs).
“Patients with Nsclc and Egfr mutations have few therapeutic options available, both in terms of number and efficacy. In this context, the data presented at the recent Asco conference on the primary analysis of the Paloma-III study and on the secondary analysis of the Mariposa study represent a significant step forward in the first-line treatment of this pathology, with a ‘chemo-free’ approach. These results, evaluated together, have the potential to improve the current standard of care in this context”, he comments Filippo de Marinis, director of the Thoracic Oncology Division at the IEO in Milan and president of the Italian Association of Thoracic Oncology (Aiot).
In particular – J&J details – the combination of amivantamab and lazertinib has demonstrated efficacy regardless of the biological or clinical characteristics of the patients, including those at high risk of progression (Mariposa study). Furthermore, it was demonstrated that the subcutaneous formulation of amivantamab in combination with lazertinib improved the therapeutic experience of patients, reducing administration times and decreasing infusion-related reactions by 5 times, with comparable pharmacokinetics and efficacy. to intravenous administration. Precisely on the basis of the results of the Paloma III study, the company recently submitted to the European Medicines Agency (EMA) the application for an extension of indication for amivantamab Sc in combination with lazertinib for the first-line treatment of adult patients with Advanced Nsclc with Egfr exon 19 deletion or L858R mutations, and as monotherapy in adult patients with advanced Nsclc with activating Egfr exon 20 mutations after failure of platinum-based therapy.
J&J has also been active in the field of hematological tumors for more than 2 decades, starting with multiple myeloma. “Myeloma is a complex disease for which there are still unmet therapeutic needs. Scientific research is making enormous progress in the treatment of this disease and in recent years – recalls Michele Cavo, full professor of Hematology, director of the Seràgnoli Alma Mater Institute of Hematology Studiorum – University of Bologna, Irccs Aou Bologna – New therapies have significantly improved the survival and quality of life of patients. Furthermore, the availability of these new drugs has changed the therapeutic approach, making it increasingly personalized and allowing doctors to guide the therapeutic choice for each patient not only on the basis of efficacy, but also of tolerability and method of administration”.
At the Asco and Eha 2024 conferences, J&J presented more than 40 works dedicated to immunotherapies for myeloma, from the anti-CD38 monoclonal antibody to bispecifics and Car-Ts. First of all – the note reports – the results of the final analysis on survival of the phase 3 Maia study were presented which evaluated the effectiveness of the treatment based on daratumumab – the first anti-CD38 monoclonal antibody – in combination with lenalidomide and dexamethasone ( D-Rd) in patients with newly diagnosed multiple myeloma who are not eligible for high-dose chemotherapy and autologous stem cell transplantation. The median overall survival (median Os) observed was 7.5 years and appears to be the longest survival reported in patients not eligible for transplant, with a reduction in the risk of death of 33% compared to treatment with lenalidomide and dexamethasone alone ( Rd), therefore indicating that the inclusion of daratumumab in the basic combination is fundamental for the first line of treatment of these patients.
Promising data have also been presented in the field of advanced therapies, the note continues: bispecific antibodies and the Car-T-based therapy, ciltacabtagene-autoleucel (cilta-cel). With a median follow-up of 2.5 years, the MajesTEC-1 study is the study with the longest observation period ever conducted for a bispecific antibody. Specifically, the study showed long-lasting and profound responses in patients with relapsed and refractory multiple myeloma treated with teclistamab – a bispecific antibody directed against the B cell maturation antigen (Bcma) – present on the surface of neoplastic cells and the CD3 antigen present on the surface of T lymphocytes, even with a reduction in the frequency of drug administration. The results of the MonumenTAL-1 study, however, showed that J&J’s second bispecific antibody, talquetamab – the first to target the Gprc5D (G-protein coupled receptor family C group 5 member D) receptor present on neoplastic cells – is associated to a high survival rate of 57-67% at 24 months and to moderate rates of severe infection that reduce over time.
But not only that, speaking of advanced therapies, data from the phase 3 Cartitude-4 study, for which J&J recently received the extension of indication for cilta-cel from the second line of treatment, suggest that this cell therapy significantly improves the Pfs, compared to standard therapies of pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd), of patients with lenalidomide-refractory multiple myeloma after a prior line of therapy (Lot), including patients with multiple myeloma at high functional risk (Fhr), and with a reduction in the risk of disease progression of 73% compared to the non-experimental arm.
In addition to multiple myeloma, J&J is engaged in research into another blood cancer, chronic lymphocytic leukemia (CLL). In particular, ibrutinib – the first Bruton’s tyrosine kinase (Btk) inhibitor to be made available for the treatment of CLL – continues to demonstrate benefits for patients affected by this hematological cancer with the results of two long-term studies. In particular, the Resonate-2 study, with 10-year follow-up and the longest-term efficacy and safety data ever reported for any Btk inhibitor in CLL, showed continued benefits in terms of OS and Pfs of monotherapy with ibrutinib in first line compared to chlorambucil treatment. The updated results of the Captivate study, at a follow-up of over 5 years, evaluated J&J’s Btk inhibitor in combination with venetoclax in patients with CLL with high-risk genomic characteristics, showing a significant benefit in terms of Pfs. Furthermore, retreatment with ibrutinib provided promising responses in relapsed patients who required subsequent therapy after the all-oral fixed-duration regimen.
“The long-term results on ibrutinib presented at the European Hematology Congress represent further confirmation of the effectiveness of this Btk inhibitor in chronic lymphocytic leukemia – remarks Anna Maria Frustaci, medical director of the Complex Hematology Unit, Asst Grande Ospedale Metropolitano Niguarda – Today, the data available is very ‘robust’ and is based not only on the longest follow-up recorded for this class of molecules, but also on the very high number of patients treated in clinical trials, and even more so in clinical practice this is added to the important innovation of the combination therapy of ibrutinib and venetoclax which brings together the two most important and effective molecules for the treatment of CLL and the ones best known to us clinicians”.
“The updated results on this combination presented at the European Hematology Congress provide further information, especially for those patients most at high risk. We would also like to remind you that it is a completely oral treatment, without chemotherapy, which allows you to avoid having to resort to hospitalizations or intravenous infusions, improving the management of the therapy for both the patient and the doctor and the caregiver”, concludes the specialist.
