Αρχική World News Amivantamab Demonstrates Robust Efficacy in Patients with EGFR Exon 20 Insertion-Mutated NSCLC

Amivantamab Demonstrates Robust Efficacy in Patients with EGFR Exon 20 Insertion-Mutated NSCLC

Amivantamab demonstrated robust and durable responses in patients with epidermal growth factor receptor Exon 20 insertion (EGFR Exon20ins)-mutated non-small cell lung cancer (NSCLC) after progression on standard-of-care platinum-based chemotherapy. Amivantamab exhibited a tolerable safety profile consistent with on-target inhibition of EGFR and MET pathways. The findings from the CHRYSALIS study are published by Prof. Byoung Chul Cho of the Yonsei Cancer Center, Yonsei University College of Medicine in Seoul, South Korea and colleagues on 2 August 2021 in the Journal of Clinical Oncology.

Activating EGFR mutations are a major oncogenic driver in NSCLC with 85% of cases arising from an Exon 19 deletion or Exon 21 L858R point substitution. The third most frequently occurring Exon20ins mutations are characterised by in-frame insertions and duplications near the C-helix of the EGFR kinase domain. EGFR Exon20ins mutations are molecularly heterogeneous with more than 100 variants identified by next-generation sequencing.

With some geographical variation, EGFR Exon20ins mutations are detected in up to 4% of all advanced NSCLC and in 4-12% of EGFRmutated NSCLC. EGFR Exon20ins are more common in tumours among never smokers. Most of the Exon20ins mutations exhibit de novo resistance to the currently approved first-line EGFR tyrosine kinase inhibitors (TKIs) erlotinib, gefitinib, afatinib, and osimertinib. Mechanisms of TKI resistance are multifactorial.

Amivantamab, an EGFR-MET bispecific antibody with immune cell–directing activity, binds to each receptor’s extracellular domain, bypassing resistance at the TKI binding site.

CHRYSALIS is a phase I, open-label, dose-escalation, and dose-expansion study, which included patients with EGFR Exon20ins NSCLC. The primary endpoints were dose-limiting toxicity and overall response rate (ORR). In the Journal of Clinical Oncology article, the study team reported findings from the post-platinum EGFR Exon20ins NSCLC population treated at the recommended phase II dose of 1,050 mg amivantamab (1,400 mg ≥ 80 kg) given once weekly for the first 4 weeks and then once every 2 weeks starting at week 5.

In the efficacy population (n = 81), the median age was 62 years (range, 42-84 years). Almost half, 40 patients (49%) were Asian. The median number of previous lines of therapy was 2 (range, 1-7).

The ORR was 40% (95% confidence interval [CI] 29 to 51), including three complete responses, with a median duration of response of 11.1 months (95% CI 6.9 to not reached). The median progression-free survival was 8.3 months (95% CI 6.5 to 10.9).

In the safety population (n = 114), the most common adverse events were rash in 98 patients (86%), infusion-related reactions in 75 (66%), and paronychia in 51 (45%). The most common grade 3-4 adverse events were hypokalaemia in six patients (5%) and rash, pulmonary embolism, diarrhoea, and neutropenia in four (4%) each. Treatment-related dose reductions and discontinuations were reported in 13% and 4% of patients.

The authors wrote that their results provide proof of concept that the EGFR can be effectively targeted through the extracellular domain for mutations that are resistant to EGFR TKIs, including EGFR Exon20ins mutations. Amivantamab is the first bispecific antibody to demonstrate clinically meaningful efficacy in patients with EGFR Exon20ins-mutated NSCLC. Amivantamab has the potential to target other EGFR-driven and/or MET-driven tumours, as monotherapy or in combination. Combined approaches are under investigation.

Jens Köhler and Pasi Jänne of the Dana-Farber Cancer Institute, Harvard Medical School in Boston, MA, US wrote in an article about understanding the pathway that for moving amivantamab into the first-line, either as a single agent or in combination with chemotherapy (currently under investigation in the PAPILLON study), a comprehensive analysis of the impact of EGFR Exon20ins on baseline EGFR and MET expression and the subsequent validation of treatment predictors will be essential.

There is some initial evidence that a high combined EGFR/MET immunohistochemistry score enriches for amivantamab responders after progression with osimertinib. Drs Köhler and Jänne wrote that systematic molecular analyses using on-treatment biopsies, cell-free DNA, or circulating tumour cells at progression are warranted to better understand the biology of efficacy and resistance.

The study was funded by Janssen R&D LLC.

References

Park K, Haura EB, Leighl NB, et al. Amivantamab in EGFR Exon 20 Insertion–Mutated Non–Small-Cell Lung Cancer Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study: JCO; Published online 2 August 2021. DOI: 10.1200/JCO.21.00662

Köhler J, Jänne P. Amivantamab: Treating EGFR Exon 20–Mutant Cancers With Bispecific Antibody-Mediated Receptor Degradation. JCO; Published online 2 August 2021. DOI: 10.1200/JCO.21.01494

Source

NEWSLETTER

Συμπληρώστε το email σας για να λαμβάνετε τις σημαντικότερες ειδήσεις από το ogkologos.com

Βρείτε μας

2,449ΥποστηρικτέςΚάντε Like
57ΑκόλουθοιΑκολουθήστε

Διαβαστε Επίσης

Καρκίνος και Κορωνοϊός (COVID-19) ΜΕΡΟΣ Α

Εάν είστε καρκινοπαθής, το ανοσοποιητικό σας σύστημα μπορεί να μην είναι τόσο ισχυρό όσο κανονικά, έτσι μπορεί να ανησυχείτε για τους κινδύνους που σχετίζονται...

ΠΑΓΚΟΣΜΙΑ ΗΜΕΡΑ ΚΑΡΚΙΝΟΥ

Η Παγκόσμια Ημέρα Κατά του Καρκίνου καθιερώθηκε με πρωτοβουλία της Διεθνούς Ένωσης κατά του Καρκίνου (UICC), που εκπροσωπεί 800 οργανώσεις σε 155 χώρες του...

ΕΞΕΛΙΞΕΙΣ ΣΤΗ ΘΕΡΑΠΕΙΑ ΤΟΥ ΜΗ-ΜΙΚΡΟΚΥΤΤΑΡΙΚΟΥ ΚΑΡΚΙΝΟΥ ΤΟΥ ΠΝΕΥΜΟΝΑ (ΜΜΚΠ)

ΕΞΕΛΙΞΕΙΣ ΣΤΗ ΘΕΡΑΠΕΙΑ ΤΟΥ ΜΗ-ΜΙΚΡΟΚΥΤΤΑΡΙΚΟΥ ΚΑΡΚΙΝΟΥ ΤΟΥ ΠΝΕΥΜΟΝΑ (ΜΜΚΠ) Γράφει ο Δρ Παπαδούρης Σάββας, Παθόλογος-Ογκολόγος   Ο ΜΜΚΠ βρίσκεται αναλογικά στο 80% και πλέον του συνολικού...

Διατρέχουν όντως οι καρκινοπαθείς μεγαλύτερο κίνδυνο λόγω κοροναϊού;

Σε πρακτικό επίπεδο, τα δεδομένα των σχετικών μελετών υποδηλώνουν ότι η χημειοθεραπεία ή οι άλλες αντι-νεοπλασματικές θεραπείες δεν αυξάνουν σημαντικά τον κίνδυνο θνησιμότητας από...

FDA: Η ακτινοβολία των smartphones δεν προκαλεί καρκίνο

Σε μια νέα έκθεσή της, η Υπηρεσία Τροφίμων και Φαρμάκων (FDA) των ΗΠΑ αναφέρει ότι επανεξέτασε τις σχετικές επιστημονικές έρευνες που δημοσιεύθηκαν τα τελευταία...

Νέα ανακάλυψη, νέα ελπίδα για τον καρκίνο

Ένα νεοανακαλυφθέν τμήμα του ανοσοποιητικού μας συστήματος θα μπορούσε να αξιοποιηθεί για την αντιμετώπιση όλων των ειδών καρκίνου, σύμφωνα με επιστήμονες του πανεπιστημίου Cardiff...
- Advertisment -

Ροή Ειδήσεων

Combining existing drugs improves prostate cancer survival

Adding abiraterone to standard hormone therapy improves survival for men with high-risk prostate cancer that’s not spread elsewhere in the body. “Today’s results are the...

New Combination of Old Drugs Improves Survival in Patients with Prostate Cancer [ESMO Congress 2021 Press Release]

LBA4_PR - Abiraterone acetate plus prednisolone (AAP) with or without enzalutamide (ENZ) added to androgen deprivation therapy (ADT) compared to ADT alone for men...

Immunotherapy Prolongs Survival in Recurrent, Persistent or Metastatic Cervical Cancer [ESMO Congress 2021 Press Release]

LBA2_PR - Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for persistent, recurrent, or metastatic cervical cancer: Randomized, double-blind, phase 3 KEYNOTE-826 study N. Colombo1, C....

Woman Diagnosed with Breast Cancer at 33 Launches Self-Examination App

Jessica Baladad has had a long history with self-examinations after a breast cancer scare in her early 20s. This habit helped save her life,...

Extended Adjuvant Treatment with Letrozole Results in Longer Survival in Postmenopausal Patients with Breast Cancer

According to results from a prospective, open-label, phase III study conducted in 69 Italian hospitals within the Gruppo Italiano Mammella among the postmenopausal patients...

Foodie Fridays: Apple Bok Choy Salad

While the temps may still be in the 80’s, apple season is upon us! Give this Apple Bok Choy salad a try!  It is...