On October 11, 2023 AstraZeneca reported its ambition to eliminate cancer as a cause of death with new data across its robust portfolio and pipeline at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress, 20 to 24 October 2023 (Press release, AstraZeneca, OCT 11, 2023, View Source [SID1234635822]).
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Nearly 100 abstracts will feature 19 approved and potential new medicines from AstraZeneca including two late-breaking Presidential Symposia and 26 oral presentations. Highlights include:
TROPION-Lung01 Phase III trial of AstraZeneca and Daiichi Sankyo’s datopotamab deruxtecan (Dato-DXd) in patients with previously treated advanced non-small cell lung cancer (NSCLC) (Presidential Symposium, Monday 23 October).
TROPION-Breast01 Phase III trial of datopotamab deruxtecan in patients with previously treated inoperable or metastatic hormone receptor (HR)-positive, HER2-low or negative breast cancer (Presidential Symposium, Monday 23 October).
FLAURA2 Phase III trial of Tagrisso (osimertinib) plus chemotherapy in EGFR-mutated (EGFRm) advanced NSCLC including safety and central nervous system metastases outcomes. Results were recently presented from the progression-free survival (PFS) primary analysis.
DUO-E Phase III trial of Imfinzi (durvalumab) plus platinum-based chemotherapy followed by either Imfinzi monotherapy or Imfinzi plus Lynparza (olaparib) as maintenance therapy in newly diagnosed advanced or recurrent endometrial cancer.
MATTERHORN Phase III trial of Imfinzi plus neoadjuvant chemotherapy (before surgery) for patients with resectable, early-stage and locally advanced (Stages II, III, IVA) gastric and gastroesophageal junction (GEJ) cancers.
DESTINY-PanTumor02 Phase II trial of AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) in previously treated HER2-expressing advanced solid tumours including PFS and overall survival (OS) data from the primary analysis.
Three bispecifics: data from several presentations will highlight the Company’s robust clinical programme of novel immuno-oncology (IO) bispecific antibodies including data for volrustomig in advanced clear cell renal cell carcinoma (MEDI5752, targeting PD-1/CTLA-4), and data for rilvegostomig (AZD2936, targeting PD-1/TIGIT) and sabestomig (AZD7789, targeting PD-1/TIM3) in lung cancer.
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "At ESMO (Free ESMO Whitepaper), we are building on the potential of our antibody drug conjugate portfolio with results from the TROPION-Lung01 and TROPION-Breast01 Phase III trials demonstrating the promise of datopotamab deruxtecan for patients across multiple cancer types in two back-to-back Presidential Symposia. These first pivotal data from our robust clinical programme are just the beginning for this TROP2-directed antibody drug conjugate, which we believe could replace conventional chemotherapy for many patients."
Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: "Our key data at ESMO (Free ESMO Whitepaper) demonstrate our commitment to redefining cancer care across a growing number of tumour types with high unmet need. Across lung, breast, gynaecologic and gastrointestinal cancers, the first data will be presented from four different pivotal trials which will raise the bar for patients with multiple medicines from our industry-leading portfolio and highlight the power of novel combinations."
Datopotamab deruxtecan takes centre stage with promising data in lung and breast cancers
A Presidential Symposium will highlight PFS data from the TROPION-Lung01 Phase III trial evaluating datopotamab deruxtecan in patients with previously treated advanced NSCLC. In July, datopotamab deruxtecan became the first antibody drug conjugate to demonstrate a statistically significant improvement in PFS and a trend in improvement for OS compared to docetaxel, the current standard-of-care chemotherapy. Additionally, a mini-oral presentation will feature initial results from the TROPION-Lung05 Phase II trial evaluating datopotamab deruxtecan in patients with heavily pretreated advanced NSCLC with actionable genomic mutations (AGA). There are currently no TROP2-directed antibody drug conjugates approved for the treatment of patients with lung cancer.
Another Presidential Symposium will showcase data from the TROPION-Breast01 Phase III trial of datopotamab deruxtecan in patients with inoperable or metastatic hormone receptor (HR)-positive, HER2-low or negative breast cancer previously treated with endocrine-based therapy and at least one systemic therapy. In September, datopotamab deruxtecan demonstrated a statistically significant and clinically meaningful improvement in PFS and a trend in improvement for OS compared to investigator’s choice of chemotherapy.
Lastly, a mini-oral presentation will highlight updated safety and efficacy results from the BEGONIA Phase Ib/II trial of datopotamab deruxtecan plus Imfinzi in patients with previously untreated unresectable, locally advanced or metastatic triple-negative breast cancer (TNBC), including duration of response. Early data from the trial presented previously demonstrated promising clinical responses in this setting, regardless of PD-L1 expression (low and high tumours).
Imfinzi combinations enter new tumour types and continue delivering in lung and biliary tract cancers
A late-breaking oral presentation will feature PFS data from the DUO-E Phase III trial evaluating treatment with Imfinzi and chemotherapy followed by either Imfinzi plus Lynparza or Imfinzi alone as maintenance therapy in patients with newly diagnosed advanced or recurrent endometrial cancer. High-level results recently announced showed both regimens demonstrated a statistically significant and clinically meaningful improvement in PFS compared to standard-of-care chemotherapy alone, with greater clinical benefit observed with the combination of Imfinzi and Lynparza as maintenance treatment.
Another late-breaking oral presentation will highlight pathologic complete response (pCR) data from the MATTERHORN Phase III trial of Imfinzi added to standard-of-care FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) neoadjuvant chemotherapy for patients with resectable, early-stage and locally advanced gastric and GEJ cancers versus neoadjuvant therapy alone. High-level interim results demonstrated a statistically significant and clinically meaningful improvement in the key secondary endpoint of pCR. This is the first global Phase III trial of an immunotherapy and FLOT chemotherapy combination to demonstrate clinical benefit in this setting. The trial is continuing to assess the primary endpoint of event-free survival.
Also in gastrointestinal cancers, two poster presentations of new data from the TOPAZ-1 Phase III trial will further reinforce the benefit of Imfinzi plus chemotherapy as a 1st-line standard-of-care treatment for advanced biliary tract cancer. Results will be shared from an exploratory analysis of an extended cohort of TOPAZ-1 patients enrolled in China. Additionally, results will be shared from an exploratory analysis assessing the impact of prognostic or predictive factors of OS in the trial.
A late-breaking mini-oral presentation in lung cancer will report exploratory analyses from the AEGEAN Phase III trial of Imfinzi-based treatment before and after surgery in patients with resectable NSCLC, evaluating potential associations between circulating tumour DNA (ctDNA) and neoadjuvant treatment responses.
Extending the benefits of Enhertu across HER2-expressing tumours
New data from the DESTINY-PanTumor02 and DESTINY-PanTumor01 Phase II trials will underscore the potential of Enhertu for previously treated patients with HER2-expressing or HER2-mutated advanced solid tumours, respectively, who currently have no targeted treatment options.
A late-breaking mini-oral presentation of primary results from DESTINY-PanTumor02 will highlight efficacy and safety outcomes for Enhertu in patients with HER2-expressing solid tumours. In July, high-level primary analysis results showed Enhertu demonstrated clinically meaningful PFS and OS, as well as provided robust and durable tumour responses across multiple HER2-expressing solid tumours in the trial. Additionally, a poster presentation will share exploratory biomarker analyses of HER2 expression and gene amplification in tissue and baseline plasma ctDNA.
A further oral presentation will feature the first report of primary results from DESTINY-PanTumor01 in patients with solid tumours that have specific HER2-activating mutations.
A mini-oral presentation will feature post-hoc pooled efficacy and safety analyses of the DESTINY-Lung01 and DESTINY-Lung02 Phase II trials of Enhertu in patients with HER2-mutated metastatic NSCLC with and without brain metastases.
Several presentations will feature new data from the DESTINY-Breast clinical programme for Enhertu, including its efficacy in patients with brain metastases.
Progressing next-wave treatments including best-in-class bispecifics
Several presentations will share data from AstraZeneca’s portfolio of novel IO bispecific antibodies, underscoring the Company’s investment in a robust clinical programme for this next wave of IO therapy. These include:
A mini-oral presentation of data from a Phase Ib trial of volrustomig (MEDI5752), a PD-1/CTLA-4 bispecific antibody, in the 1st-line treatment of patients with advanced clear cell renal cell carcinoma.
Another mini-oral presentation of safety and preliminary efficacy results from the Phase I/IIa first-in-human trial of sabestomig (AZD7789), a PD-1/TIM-3 bispecific antibody, in patients with Stages IIIb-IV NSCLC resistant to previous anti-PD(L)1 therapy.
A poster presentation of data from the ARTEMIDE-01 Phase I trial assessing rilvegostomig (AZD2936), a PD-1/TIGIT bispecific antibody, in patients with advanced or metastatic NSCLC.
Collaboration in the scientific community is critical to improving outcomes for patients. AstraZeneca is collaborating with Daiichi Sankyo Company Limited to develop and commercialise Enhertu and datopotamab deruxtecan, and with MSD (Merck & Co., Inc. in the US and Canada) to develop and commercialise Lynparza both as a monotherapy and in combination with other potential medicines. Independently, the companies are developing Lynparza in combination with their respective PD-L1 and PD-1 medicines, Imfinzi and pembrolizumab, in a number of tumour types.
Key AstraZeneca presentations during ESMO (Free ESMO Whitepaper) 2023
Lead Author
Abstract Title
Presentation details (CEST)
Antibody drug conjugates
Datopotamab deruxtecan
Ahn, M (presented by Lisberg, A)
Datopotamab deruxtecan (Dato-DXd) vs docetaxel in previously treated advanced/metastatic
(adv/met) non-small cell lung cancer (NSCLC): Results of the randomized phase 3 study
TROPION-Lung01
Abstract #LBA12
Presidential 3
23 October 2023
04:42 PM
Bardia, A
Datopotamab deruxtecan (Dato-DXd) vs chemotherapy in previously-treated inoperable or metastatic hormone receptor-positive, HER2-negative (HR+/HER2–) breast cancer (BC): Primary results from the randomised Phase 3 TROPION-Breast01 trial
Abstract #LBA11
Presidential 3
23 October 2023
04:30 PM
Paz-Ares, L
TROPION-Lung05: Datopotamab deruxtecan (Dato-DXd) in previously treated non-small cell lung cancer (NSCLC) with actionable genomic alterations (AGAs)
Abstract #1341MO
Mini oral session 1 – NSCLC, metastatic
21 October 2023
09:30 AM
Schmid, P
Datopotamab deruxtecan (Dato-DXd) + durvalumab (D) as first-line (1L) treatment for unresectable locally advanced/metastatic triple-negative breast cancer (a/mTNBC): updated results from BEGONIA, a phase 1b/2 study
Abstract #379MO
Mini oral session – Breast cancer, metastatic
22 October 2023
08:30 AM
Enhertu
Modi, S
Trastuzumab Deruxtecan (T-DXd) Versus Treatment of Physician’s Choice (TPC) in patients (pts) With HER2-Low Unresectable and/or Metastatic Breast Cancer (mBC): Updated Survival Results of the Randomized, Phase 3 DESTINY-Breast04 Study
Abstract #376O
Proffered Paper session – Breast cancer, metastatic
21 October 2023
10:25 AM
Hurvitz, S
A Pooled Analysis of Trastuzumab Deruxtecan (T-DXd) in Patients (pts) With HER2-Positive (HER2+) Metastatic Breast Cancer (Mbc) With Brain Metastases (BMs) from DESTINY-Breast (DB) -01, 02, and -03
Abstract #377O
Proffered Paper session – Breast cancer, metastatic
21 October 2023
10:55 AM
Li, B
Efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients (pts) with solid tumors harboring specific HER2-activating mutations (HER2m): primary results from the international phase 2 DESTINY-PanTumor01 (DPT-01) study
Abstract #654O
Proffered Paper session – Developmental therapeutics
22 October 2023
09:20 AM
Li, B
Trastuzumab Deruxtecan (T-DXd) in Patients (pts) With HER2 (ERBB2)-Mutant (HER2m) Metastatic Non–Small Cell Lung Cancer (NSCLC) With and Without Brain Metastases (BMs): Pooled Analyses From DESTINY-Lung01 and DESTINY-Lung02
Abstract #1321MO
Mini oral session 2 – NSCLC, metastatic
22 October 2023
0:9:05 AM
Meric-Bernstam, F
Trastuzumab deruxtecan (T-DXd) for pretreated patients (pts) with HER2-expressing solid tumors: primary analysis from the DESTINY-PanTumor02 (DP-02) study
Abstract #LBA34
Mini oral session – Developmental therapeutics
23 October 2023
04:40 PM
Smit, E
Baseline Circulating Tumor DNA (ctDNA) Biomarker Analysis of Patients With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Non–Small Cell Lung Cancer (NSCLC) Treated With Trastuzumab Deruxtecan (T-DXd)
Abstract #151P
e-Poster – Biomarkers (agnostic)
21 October 2023
Tsurutani, J
Subgroup Analysis of Patients (pts) With HER2-Low Metastatic Breast Cancer (mBC) With Brain Metastases (BMs) at Baseline From DESTINY-Breast04, A Randomized Phase 3 Study of Trastuzumab Deruxtecan (T-DXd) vs Treatment of Physicians Choice (TPC)
Abstract #388P
e-Poster – Breast cancer, metastatic
21 October 2023
AZD5335
Meric-Bernstam, F
FONTANA: A Phase 1/2a study of AZD5335 as monotherapy and in combination with anti-cancer agents in patients with solid tumours
Abstract #819TiP
e-Poster – Gynaecological cancers
22 October 2023
Immuno-oncology
Westin, S
Durvalumab (durva) plus carboplatin/paclitaxel (CP) followed by maintenance (mtx) durva ± olaparib (ola) as a first line (1L) treatment for newly diagnosed advanced or recurrent endometrial cancer (EC): results from the Phase III DUO-E/GOG-3041/ENGOT-EN10 trial
Abstract #LBA41
Proffered Paper session 2 – Gynaecological cancers
21 October 2023
09:15 AM
Janjigian, Y (presented by Al-Batran, S)
Pathological complete response to 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) chemotherapy with or without durvalumab in resectable gastric and gastroesophageal junction cancer (GC/GEJC): Interim results of the phase 3, randomised, double-blind MATTERHORN study
Abstract #LBA73
Proffered Paper session 1 – Gastrointestinal tumours, upper digestive
20 October 2023
02:10 PM
Garassino, M
Durvalumab (durva) after sequential chemoradiotherapy (CRT) in patients (pts) with unresectable Stage III NSCLC: Final analysis from PACIFIC-6
Abstract #LBA61
Mini oral session 2 – Non-metastatic NSCLC and other thoracic malignancies
23 October 2023
03:20 PM
Reck, M
Associations of ctDNA clearance and pathological response with neoadjuvant treatment in patients with resectable NSCLC from the phase 3 AEGEAN trial
Abstract #LBA59
Mini oral session 2 – Non-metastatic NSCLC and other thoracic malignancies
23 October 2023
03:00 PM
Filippi, A
Durvalumab after radiotherapy (RT) in patients with unresectable Stage III NSCLC ineligible for chemotherapy (CT): Primary results from the DUART study
Abstract #LBA62
Mini oral session 2 – Non-metastatic NSCLC and other thoracic malignancies
23 October 2023
03:30 PM
Besse, B
Safety and preliminary efficacy of AZD7789, a bispecific antibody targeting PD-1 and TIM-3, in patients (pts) with stage IIIB-IV non-small cell lung cancer (NSCLC) with previous anti-PD-L(1) therapy
Abstract #1313MO
Mini oral session 1 – NSCLC, metastatic
21 October 2023
09:15 AM
Voss, M
MEDI5752 (volrustomig), a novel PD-1/CTLA-4 bispecific antibody, in the first-line (1L) treatment of 65 patients (pts) with advanced clear cell renal carcinoma (aRCC)
Abstract #1883MO
Mini oral session – Genitourinary tumours, non-prostate
22 October 2023
11:25 AM
Brandão, M
Preliminary efficacy and safety of rilvegostomig (AZD2936), a bispecific antibody targeting PD-1 and TIGIT, in checkpoint inhibitor (CPI)-pretreated advanced/metastatic non-small-cell lung cancer (NSCLC): ARTEMIDE-01
Abstract #1446P
e-Poster – NSCLC, metastatic
23 October 2023
He, A
Potentially prognostic factors of overall survival in advanced biliary tract cancer in the randomised Phase 3 TOPAZ-1 study
Abstract #102P
e-Poster – Biliary tract cancer, incl. cholangiocarcinoma
23 October 2023
Qin, S
Efficacy and safety of durvalumab plus gemcitabine and cisplatin in Chinese participants with advanced biliary tract cancer: extension cohort of the Phase 3, randomised, double-blind, placebo-controlled, global TOPAZ-1 study
Abstract #98P
e-Poster – Biliary tract cancer, incl. cholangiocarcinoma
23 October 2023
Tumour drivers and resistance
Jänne, P
Circulating tumour DNA (ctDNA) profiling in patients (pts) with EGFR-mutated (EGFRm) advanced NSCLC receiving osimertinib + chemotherapy vs osimertinib monotherapy: FLAURA2
Abstract #LBA68
Mini oral session 1 – NSCLC, metastatic
21 October 2023
08:30 AM
DNA damage response
Mehra, N
Efficacy of Olaparib (ola) + abiraterone (abi) vs placebo (pbo) + abi in the non-BRCA mutation (non-BRCAm) subgroup of patients (pts) with metastatic castration-resistant prostate cancer (mCPRC) in the PROpel trial
Abstract #1805P
e-Poster – Prostate cancer
22 October 2023