Expert Answers to HCP Questions on CAR T-Cell Therapy

The third and final episode in a 3-part series covers the safety profile of and considerations for managing adverse events associated with HER3-targeted antibody–drug conjugates, including patritumab deruxtecan (HER3-DXd) and others, in the setting of lung cancer. 

Presenters in this series include:

Rebecca S. Heist, MD, MPH
Associate Professor of Medicine
Harvard Medical School
Medical Oncology
Massachusetts General Hospital
Boston, Massachusetts

Helena Yu, MD
Associate Attending
Department of Medicine
Memorial Sloan Kettering Cancer Center
New York, New York

Supported by an educational grant from Daiichi Sankyo, Inc. 

Link to full program, including a downloadable highlights slideset:
https://bit.ly/48ecElW

This second episode in a 3-part series on HER3-targeted agents in NSCLC covers current clinical trials with HER3-targeted therapy, including:

• Recent data on patritumab deruxtecan (HER3-DXd) in the HERTHENA-Lung01 trial
• The EGFRxHER3 bispecific antibodies BL-B01D1 and izalontamab
• The HER2xHER3 bispecific antibody zenocutuzumab
• The HER3-targeted antibody–drug conjugate SHR-A2009 

Presenters in this series include:

Rebecca S. Heist, MD, MPH
Associate Professor of Medicine
Harvard Medical School
Medical Oncology
Massachusetts General Hospital
Boston, Massachusetts

Helena Yu, MD
Associate Attending
Department of Medicine
Memorial Sloan Kettering Cancer Center
New York, New York

Supported by an educational grant from Daiichi Sankyo, Inc. 

Link to full program, including a downloadable highlights slideset: 
https://bit.ly/48ecElW

This first episode in a 3-part series tackles the role of HER3 in cancer, specifically in NSCLC, and how HER3 can be effectively targeted with ADCs.

Presenters in this series include:

Rebecca S. Heist, MD, MPH
Associate Professor of Medicine
Harvard Medical School
Medical Oncology
Massachusetts General Hospital
Boston, Massachusetts

Helena Yu, MD
Associate Attending
Department of Medicine
Memorial Sloan Kettering Cancer Center
New York, New York
Supported by an educational grant from Daiichi Sankyo, Inc. 

Link to full program, including a downloadable highlights slideset:
https://bit.ly/48ecElW

In this episode, Brian Slomovitz, MD, MS, FACOG, and Keiichi Fujiwara, MD, PhD, share their thoughts and opinions on seminal data presented at the 2023 IGCS annual meeting for endometrial, ovarian, and cervical cancers, including:

• Phase III NRG GY018 trial of carboplatin and paclitaxel with or without pembrolizumab followed by pembrolizumab or placebo maintenance for 2 years in patients with measurable stage III/IVA, stage IVB, or recurrent endometrial cancer. 
• Phase III ENGOT-EN6/GOG-3031/RUBY trial of carboplatin and paclitaxel with or without dostarlimab followed by dostarlimab or placebo maintenance for 3 years in patients with primary advanced or recurrent endometrial cancer. 
• Results from the double-blind, randomized, placebo-controlled phase III AtTEnd trial of atezolizumab plus carboplatin/paclitaxel in advanced or recurrent endometrial cancer.
• Randomized, multicenter, double-blind, placebo-controlled phase III DUO-E study of carboplatin and paclitaxel vs durvalumab plus carboplatin and paclitaxel followed by durvalumab maintenance with or without olaparib as frontline treatment of newly diagnosed, advanced, endometrial cancer.
• An international, randomized, multicenter phase III trial evaluating short-course chemotherapy followed by chemoradiation vs chemoradiation alone in patients with newly diagnosed stage IB1N+, IB2, II, IIIB, IVA squamous, adeno, adenosquamous cervical cancer (INTERLACE).
• Randomized, double-blind, placebo-controlled phase III KEYNOTE-A18 trial of pembrolizumab plus concurrent chemoradiotherapy vs placebo plus chemoradiation in patients with high-risk locally advanced cervical cancer.
• Phase III ICON8B study comparing carboplatin, paclitaxel, and bevacizumab every 3 weeks vs dose-dense weekly paclitaxel plus bevacizumab every 3 weeks in newly diagnosed high-risk epithelial ovarian cancer, either stage III (with residual disease or requiring new adjuvant chemotherapy) or stage IV.

Presenters:

Brian Slomovitz, MD, MS, FACOG
Director
Gynecologic Oncology
Mount Sinai Medical Center
Professor
Obsterics and Gynecology
Florida International University
Member, Board of Directors
GOG Foundation
Uterine Cancer Lead
GOG Partners
Miami, Florida 

Keiichi Fujiwara, MD, PhD
Professor of Gynecologic Oncology
Saitama Medical University International Medical Center
Hidaka, Japan
Professor of OBGYN
International University of Health and Welfare
Narita, Japan
This educational activity is supported by educational grants from AstraZeneca, Genmab, GlaxoSmithKline, Merck Sharp & Dohme Corp, Novocure, and Seagen. 

Link to full program, including a downloadable highlights slideset and ClinicalThought commentaries:
https://bit.ly/424E3Uq

In this episode, Jacqueline S. Garcia, MD, discusses novel agents and strategies in clinical trial development for treating patients with myelofibrosis, including:

• Navitoclax (BCL-XL/BCL-2 inhibitor)
• Pelabresib (BET inhibitor)
• Imetelstat (telomerase inhibitor)
• Luspatercept (erythroid maturation agent)
• Additional strategies

Presenter:  

Jacqueline S. Garcia, MD
Assistant Professor of Medicine
Harvard Medical School
Dana-Farber Cancer Institute
Boston, Massachusetts

Link to the full program here. https://bit.ly/47z8WCV

In this episode, Ana Marin-Niebla, MD, PhD, and Stephan Stilgenbauer, MD, discuss key trial data on the use of BTK inhibitors in CLL and MCL throughout the past year, how these studies have impacted their practice, and what data they are looking forward to in the near future. The discussion includes analyses of: 

• SHINE: First-Line Ibrutinib + Bendamustine/Rituximab Followed by Rituximab Maintenance in Older Patients With MCL 
• TRIANGLE: Ibrutinib + Chemoimmunotherapy With or Without ASCT vs Chemoimmunotherapy Followed by ASCT in Younger Patients with Previously Untreated MCL 
• ZUMA-2: Brexucabtagene Autoleucel in R/R MCL 
• BRUIN: Pirtobrutinib for Previously Treated MCL 
• GLOW: Fixed-Duration Ibrutinib + Venetoclax vs Chlorambucil + Obinutuzumab in Previously Untreated CLL 
• FLAIR: Ibrutinib + Venetoclax vs FCR in Previously Untreated CLL 
• ELEVATE-RR: Acalabrutinib vs Ibrutinib in Previously Treated CLL 
• ALPINE: Zanubrutinib vs Ibrutinib in Previously Treated CLL 
• BRUIN: Pirtobrutinib for Previously Treated CLL

Presenters: 

Ana Marin-Niebla, MD, PhD
Hematology Consultant, Lymphoma Unit
Vall d’Hebron Institute of Oncology, Hematology Department
Hospital Universitario Vall d’Hebron
Barcelona, Spain

Stephan Stilgenbauer, MD
Medical Director Comprehensive Cancer Center Ulm
Head, Early Clinical Trials Unit
Head, Division of CLL Dept. of Internal Medicine III
University Medical Center
Ulm University
Ulm, Germany

Link to full program: 
https://bit.ly/3MNaUri

In this episode, Isabelle Ray-Coquard, MD, PhD, and Ana Oaknin, MD, PhD, provide expert insights on new clinical trial data presented at the 2023 ESMO annual congress for endometrial, ovarian, and cervical cancers, including:

• Results from the double-blind, randomized, placebo-controlled phase III AtTEnd trial of atezolizumab plus carboplatin/paclitaxel in advanced or recurrent endometrial cancer
• Randomized, multicenter, double-blind, placebo-controlled phase III DUO-E study of durvalumab plus carboplatin and paclitaxel followed by durvalumab maintenance with or without olaparib as frontline treatment of newly diagnosed, advanced, endometrial cancer
• First results from a phase II biomarker-directed platform study with assigned treatments for patients with measurable persistent or recurrent platinum-resistant epithelial ovarian cancer based on tumor-specific molecular alterations (ENGOT-GYN/GOG-3051/BOUQUET)
• Randomized, double-blind, placebo-controlled phase III KEYNOTE-A18 trial of pembrolizumab plus concurrent chemoradiotherapy in patients with high-risk locally advanced cervical cancer
• An international, randomized, multicenter phase III trial evaluating short-course chemotherapy followed by chemoradiation vs chemoradiation alone in patients with newly diagnosed stage IB1N+, IB2, II, IIIB, IVA squamous, adeno, adenosquamous cervical cancer (INTERLACE)
• Primary results from the global, randomized phase III BEATcc trial of atezolizumab plus platinum-based chemotherapy + bevacizumab as frontline treatment in patients with persistent, recurrent, or metastatic cervical cancer
• Interim analysis results from the global, randomized, open-label phase III innovaTV 301 study of tisotumab vedotin vs investigator’s choice of chemotherapy in second-line or third-line recurrent/metastatic cervical cancer

Presenters:

Ana Oaknin, MD, PhD
Head of Gynaecologic Cancer Programme
Department of Medical Oncology
Vall d’ Hebron University Hospital
Vall d’Hebron Institute of Oncology
Barcelona, Spain

Isabelle Ray-Coquard, MD, PhD
President of the Gineco Group
Centre Leon Bérard
Laboratories RESHAPE 
Université Claude Bernard Lyon Est
Lyon, France

This educational activity is supported by educational grants from AstraZeneca, Genmab, GlaxoSmithKline, Merck Sharp & Dohme Corp, Novocure, and Seagen. 

Link to full program, including a downloadable highlights slideset and ClinicalThought commentaries:
https://bit.ly/424E3Uq

In this episode, Aakash Desai, MD; Narjust Florez, MD; and Paolo Tarantino, MD, discuss the biologic rationale and clinical development of agents targeting HER3 for the treatment of breast and lung cancers. The potential niche for HER3-targeted agents in these treatment landscapes is considered, with consideration of acquired resistance to previous targeted therapies and parallels to other approved antibody–drug conjugates. Their conversation covers clinical trial data from:

• Phase I/II study of patritumab deruxtecan in HR-positive/HER2-negative or triple-negative metastatic breast cancer, published by Krop and colleagues in the Journal of Clinical Oncology 
• BRE-354: A phase II study of patritumab deruxtecan in several subtypes of previously treated advanced/metastatic breast cancer, presented at ASCO 2023
• ICARUS-Breast01: A phase II study of patritumab deruxtecan in patients with HR-positive/HER2-negative or HER2-low advanced breast cancer, presented at the ESMO Breast Cancer Congress 2023
• SOLTI-TOT-HER3: A window-of-opportunity study of neoadjuvant patritumab deruxtecan for treatment-naive HER2-negative early stage breast cancer, presented at the ESMO Breast Cancer Congress 2023
• HERTHENA-Lung01: A phase II study of patritumab deruxtecan in in patients with EGFR-mutated NSCLC after treatment with osimertinib and platinum-based chemotherapy, presented at the World Conference on Lung Cancer 2023
• HERTHENA-Lung02: An ongoing phase III study of patritumab deruxtecan vs platinum-based chemotherapy after osimertinib for the treatment of EGFR-mutated NSCLC
• eNRGy: A phase I/II study of the bispecific HER2 x HER3 antibody zenocutuzumab in multiple solid tumor types with NRG1 gene fusion, presented at ASCO 2022
• DESTINY-Breast04: A phase III study of trastuzumab deruxtecan for the treatment of patients with HER2-low metastatic breast cancer, published by Modi and colleagues in the New England Journal of Medicine
• DAISY: A phase II trial of  trastuzumab deruxtecan for the treatment of breast cancer with variable levels of HER2 expression including HER2-low and HER2-zero, published by Mosele and colleagues in Nature Medicine 

Presenters:

Aakash Desai, MD
Affiliation awaiting contract

Narjust Florez, MD
Associate Director of The Cancer Care Equity Program
Thoracic Medical Oncologist, Dana-Farber Cancer Institute
Assistant Professor of Medicine, Harvard Medical School
Boston, Massachusetts

Paolo Tarantino, MD
Advanced Research Fellow
Breast Oncology Center
Dana-Farber Cancer Institute
Boston, Massachusetts
Content based on an online CME program supported by an independent educational grant from Daiichi Sankyo, Inc.

Link to full program: https://bit.ly/45UYsw3

In this episode, Dr Leslie Boyd and Adrienne Moore, a patient advocate and endometrial cancer survivor, discuss how healthcare professionals can partner with Black patients to improve the diagnosis and management of endometrial cancer (EC). Topics include:

• Data on racial disparities in EC survival
• Importance of listening to Black patients to better diagnose EC
• Financial and practical considerations regarding care
• How to help empower Black patients in shared decision-making with their care team

Presenters:

Leslie R. Boyd, MD
Associate Professor
Department of Obstetrics and Gynecology at NYU Grossman School of Medicine
Director of Division of Gynecologic Oncology
Vice Chair of Gynecology
Department of Obstetrics and Gynecology
Laura and Isaac Perlmutter Cancer Center
New York University Langone Health
New York, New York

Adrienne Moore, RT
President and Board Member
Endometrial Cancer Action Network for African-Americans
Director of Peer Support, SISTER Study
Research Coordinator, Gynecologic Oncology
Department of Obstetrics and Gynecology
University of Washington School of Medicine
Seattle, Washington

In this episode, Domenica Lorusso, MD, PhD, and Alexandra Leary, MD, PhD, provide expert insights on key updates and new clinical trial data presented at the ESGO 2023 Congress for cervical, endometrial, and ovarian cancers, including:

• Long-Term Follow Up From Phase III SIENDO Study of Selinexor vs Pbo Maintenance in Patients With TP53wt Advanced/Recurrent Endometrial Cancer 
• Global, Open-Label, Phase I/IIa of HER2-Targeting ADC (DB-1303) in Recurrent/Metastatic Endometrial Cancer
• Phase III From KEYNOTE-826: Bevacizumab Subgroup Analysis Based on Protocol Specified Final Overall Survival Results
• Phase III ICON8B: Weekly DD-CT + Bev vs Q3W CT + Bev as First Line in High-Risk Epithelial Ovarian Cancer
• HRD Testing on Cell-Free Tumor DNA From Peritoneal Fluid of Patients With Newly-Diagnosed Epithelial Ovarian Cancer

Presenters:

Alexandra Leary, MD, PhD
Co Director
Medical Oncologist and Team Leader
Gynecology Translational Research Lab
Department of Medicine
Gustave Roussy Cancer Center
Paris, France

Domenica Lorusso, MD, PhD
Associate Professor
Gynecologic Oncology Department
Clinical Research Unit
Fondazione Policlinico Gemelli IRCCS
Rome, Italy

This educational activity is supported by educational grants from AstraZeneca, GlaxoSmithKline, Merck Sharp & Dohme Corp, Novocure, Genmab, and Seagen. 

Link to full program, including a downloadable highlights slideset and ClinicalThought commentaries:
https://bit.ly/424E3Uq