Pascal Sorio, CEO of AstraZeneca.
Dave Fredrickson, Executive Vice President of Oncology at Astrazeneca, said: “This year at ESMO new evidence will show how drugs prolong patient survival in different types of tumors. Results from the phase III studies SOLO-1 and PAOLA-1 will reinforce the long-term survival benefits of PARP inhibition with olaparib in advanced ovarian cancer, and new data from durvalumab combinations in liver, biliary tract, and lung cancer will show the potential to improve outcomes for patients in these areas of high unmet need.”
Susan Galbraith, executive vice president of oncology research and development at AstraZeneca, said: “Momentum will continue to trastuzumab deruxtecan at ESMO with new data in other tumor types, including results from the phase II DESTINY-Lung02 study in HER2-mutated metastatic non-small cell lung cancer, which the FDA relied on for its recent approval. In addition, we are pleased to have been able to advance the understanding of CTLA-4 inhibition with the new analyzes presented by two phase III trials of durvalumab plus tremelimumab, HIMALAYA in liver cancer and POSEIDON in lung cancer; and for MEDI5752, our bispecific antibody targeting both PD-1 and CTLA-4 in lung cancer.”
Transformation in tumor prognosis
They will communicate in a “late” presentation mature data on disease-free survival (SLE) from the phase III ADAURA trial, in which two additional years of follow-up will be detailed in patients with early-stage (stage IB-IIIA) EGFR-mutated non-small cell lung cancer (NSCLC) treated with osimertinib in the adjuvant setting . This drug is the only targeted treatment option in this spectrum. The announcement will also present updated results from the CNS relapse and DFS models.
A late presentation will present 5-year overall survival (OS) data from the phase III PAOLA-1 trial of olaparib in combination with bevacizumab in the first-line treatment of advanced ovarian cancer in patients with homologous recombination deficiency (HRD). This is the longest follow-up of a PARP inhibitor in combination with standard of care in this setting.
In addition, seven-year OS data from the phase III SOLO1 study of olaparib as first-line maintenance therapy in advanced ovarian cancer with a BRCA mutation (BRCAm). This is the longest follow-up of any PARP inhibitor in newly diagnosed advanced ovarian cancer.
Data will also include updated two-year OS results from the phase III TOPAZ-1 trial of durvalumab plus standard chemotherapy (gemcitabine plus cisplatin) in first-line unresectable or advanced biliary tract cancer, as well as analysis of immune-mediated adverse events. TOPAZ-1 is the first phase III trial to demonstrate improved OS with a combination of immunotherapy versus chemotherapy alone in this setting.
Extend the benefit of ADCs to more patients
Several presentations will demonstrate the clinical potential of trastuzumab deruxtecan as a HER2-targeted treatment in lung, gastric and breast cancer.
The final presentation will report interim results from the phase II DESTINY-Lung02 study investigating trastuzumab deruxtecan in patients with metastatic HER2-mutated (HER2m) NSCLC who showed improvement after one or more systemic therapies. Detailed data from the phase II DESTINY-Lung01 trial, both in this setting and in patients with HER2-overexpressing NSCLC, will also be shared.
Updated data from the phase II DESTINY-Gastric02 trial in HER2-positive metastatic gastric cancer, the first trial of trastuzumab deruxtecan in Western patients with gastric cancer, will also be presented.
Data will also include subgroup analysis from the phase III DESTINY-Breast03 trial of trastuzumab deruxtecan based on disease history and prior treatments in patients with HER2 positive metastatic breast cancer previously treated with trastuzumab and a taxane. Patient-reported results from the phase III DESTINY-Breast04 trial will also highlight quality-of-life data for patients treated with trastuzumab deruxtecan in unresectable and/or metastatic HER2-low breast cancer.
Other presentations will describe studies evaluating the TROP2 receptor-targeted ADC dapotamab deruxtecan in patients with luminal, hormone receptor-positive, HER2-negative breast cancer (the phase III trial TROPION-Breast01) and in platform trial in combination with osimertinib in patients with advanced NSCLC in those who had disease progression (phase II ORCHARD study). There are currently no approved therapies targeting TROP2 for patients in these conditions.
Improving knowledge of CTLA-4 inhibition
A new analysis of the phase III HIMALAYA study will show the influence of viral etiology on the outcomes of unresectable liver cancer in patients treated with single dose of tremelimumabanti-CTLA-4 antibody added to durvalumab (STRIDE regimen).
In addition, a paper will describe the EMERALD-3 phase III study evaluating tremelimumab added to durvalumab and transarterial chemoembolization with or without lenvatinib in patients with inoperable liver cancer suitable for embolization. A presentation from the phase III POSEIDON trial in mNSCLC will show four-year OS outcomes in patients treated with a limited course of tremelimumab added to durvalumab plus chemotherapy.
Another groundbreaking presentation will reveal initial data on MEDI5752 plus chemotherapy in patients with untreated stage IIIB-IV non-squamous NSCLC. MEDI5752 is a novel bispecific antibody that simultaneously targets the immune checkpoint proteins PD-1 and CTLA-4. Bispecific antibodies are a a promising approach in immuno-oncology by combining the potential benefits of two drugs in a single antibody without the increased toxicity seen when the two drugs are given separately.
Enhancing the benefits of PARP inhibitors
In addition to data from PAOLA-1 and SOLO1, an oral presentation will disseminate updated efficacy analyzes in biomarker subgroups from the phase III PROpel trial of olaparib plus abiraterone in patients with castration-resistant prostate cancer Newly diagnosed metastases (CRPC) treated with the combination with or without homologous recombination to repair gene mutations. Olaparib is a PARP inhibitor that demonstrated a significant improvement in radiographic progression-free survival in combination with abiraterone versus abiraterone alone in first-line mCRPC, regardless of biomarker status.
In addition, they will be introduced final OS data from the phase II MEDIOLA trial of olaparib and durvalumab in ovarian cancer in platinum-sensitive relapsed patients with germline BRCA mutations and the phase IIIB OPINION study of maintenance monotherapy with olaparib in patients with platinum-resistant relapsed ovarian cancer without germline BRCA1/BRCA2 mutations.
Data will also include an extended OS analysis from the phase III POLO trial of olaparib in metastatic pancreatic cancer with a germline BRCA mutation, a disease for which no other PARP inhibitor has been approved.
incollaboration in the scientific community It is important to improve the lives of patients. For this reason, Astrazeneca is collaborating with Daiichi Sankyo Company Limited to develop and commercialize trastuzumab deruxtecan and datospotamab deruxtecan and with MSD (Merck & Co., Inc. in the United States and Canada) to develop and commercialize olaparib.
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