Several Companies Tout Lung Cancer Breakthroughs at ESMO 2021
Lung cancer is a particularly difficult cancer to treat, but several companies presented very promising data at this year’s European Society of Medical Oncology (ESMO) Congress 2021. Here’s a look.
AstraZeneca and Daiichi Sankyo’s Enhertu in NSCLC
AstraZeneca and Daiichi Sankyo presented data on their Enhertu in previously treated patients with HER2-mutant or HER2m unresectable and/or metastatic non-squamous non-small cell lung cancer (NSCLC). The results were from the HER2-mutant cohort of the pivotal DESTINY-Lung01 Phase II trial. Enhertu is a HER2-directed antibody drug conjugate.
The primary results demonstrated a confirmed objective response rate (ORR) of 54.9% in patients receiving Enhertu. One (1.1%) complete response (CR) and 49 (53.8%) partial responses (PR) were identified. An actual disease control rate (DCR) of 92.3% was observed with a decrease in tumor size in most patients.
“Despite more than 20 years of research into HER2-mutations in non-small cell lung cancer, there are currently no approved HER2-targeted therapies for non-small cell lung cancer,” said Bob Li, Memorial Sloan Kettering Cancer Center, adding, “suggesting this medicine has the potential to become the new standard of care for these patients.”
Regeneron and Sanofi’s Libtayo in Advanced NSCLC
Regeneron Pharmaceuticals and Sanofi presented positive Phase III data from a combination treatment of Libtayo (cemiplimab) with a physician’s choice of platinum-double chemotherapy in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) irrespective of histology and across all PD-L1 expression levels. The combination was compared to chemotherapy alone. The study hit the primary overall survival (OS) endpoint and all critical secondary endpoints.
“Libtayo added to chemotherapy significant improved patient outcomes, extending median overall survival to 22 months and median progression-free survival to eight months,” said Dr. Miranda Gogishvili, an oncologist at the High Technology Medical Center University Clinic, in Tbilisi, Georgia, and a trial investigator. “Exploratory analyses showed that survival improvements were seen across squamous and non-squamous histologies and in patients with reduced daily functioning, with 43% of patients having squamous disease and 84% having an ECOG 1 performance status.”
AstraZeneca’s Oleclumab or Monalizumab and Imfinzi in NSCLC
AstraZeneca also presented data from the COAST Phase II study demonstrating oleclumab or monalizumab combined with Imfinzi (durvalumab) improved PFS and ORR compared to Imfinzi alone in unresectable Stage III NSCLC patients who had not progressed after concurrent chemoradiation therapy (CRT). Oleclumab is an anti-CD73 monoclonal antibody. Monalizumab is an anti-NKG2A monoclonal antibody. Imfinzi is an anti-PD-L1 checkpoint inhibitor.
Roy S. Herbst, M.D., Ph.D., chief of Medical Oncology at Yale Cancer Center and Smilow Cancer Hospital, New Haven, CT, and chair of the COAST Steering Committee, said, “Imfinzi is the established standard of care for patients with unresectable, Stage III NSCLC, but solutions are still needed for patients who do not benefit from currently available therapies. The remarkable improvement observed with the addition of oleclumab or monalizumab to Imfinzi, along with the strong safety profile, suggests these novel combinations could further redefine outcomes for these patients.”
Janssen’s Rybrevant in Advanced EGFR-Mutant NSCLC
The Janssen Pharmaceutical Companies of Johnson & Johnson presented new analysis from the CHRYSALIS study of Rybrevant (amivantamab-vmjw) monotherapy and a combination with Lazertinib in advanced NSCLC patients with epidermal growth factor receptor (EGFR) mutations who progressed after Osimertinib. The data demonstrated that patients receiving the combination therapy had higher activity and longer duration of response (DOR), even in patients who were found to be resistant to third-generation EGFR tyrosine kinase inhibitors (TKIs).
“This analysis shows that targeting two domains of EGFR using amivantamab and Lazertinib combination therapy demonstrated higher and more durable response than targeting only one domain,” said Natasha B. Leighl, M.D., Lung Medical Oncology Lead, Princess Margaret Cancer Centre in Toronto, Canada, and presenting study investigator.
Mirati’s Adagrasib in NSCLC with KRASG12C Mutations
Mirati Therapeutics announced positive topline results from the Phase II KRYSTAL-1 trial of adragrasib in patients with advanced NSCLC harboring the KRASG12C mutation after previous systemic therapy. The data showed that adagrasib 600mg BID had an ORR of 43% and a DCR of 80% based on central independent review as of June 15, 2021. The median follow-up was nine months. Most, 98.3%, of the patients received adagrasib after treatment with immunotherapy and chemotherapy.
“The KRAS mutation has historically been challenging to target, leaving patients with limited treatment options,” said Charles M. Baum, M.D., Ph.D., president and chief executive officer of Mirati. “These positive topline data further strengthen our belief in adagrasib as a potentially differentiated therapy for patients with non-small cell lung cancer harboring the KRASG12C mutation.”
The company plans to submit a New Drug Application to the U.S. Food and Drug Administration (FDA) in the fourth quarter of this year.