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Meet The ProfessorManagement of Lung Cancer

Professor Tony SK Mok, MDChairman, Department of Clinical Oncology

The Chinese University of Hong KongHong Kong, China

Commercial Support

This activity is supported by an educational grant from AstraZeneca Pharmaceuticals LP.

Dr Love — Disclosures

Dr Love is president and CEO of Research To Practice. Research To Practice receives funds in the form of educational grants to develop CME activities from the following commercial interests: AbbVie Inc, AcertaPharma — A member of the AstraZeneca Group, Adaptive Biotechnologies Corporation, Agendia Inc, AgiosPharmaceuticals Inc, Amgen Inc, Array BioPharma Inc, a subsidiary of Pfizer Inc, Astellas, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Biodesix Inc, bioTheranostics Inc, Blueprint Medicines, Boehringer Ingelheim Pharmaceuticals Inc, Bristol-Myers Squibb Company, Celgene Corporation, Clovis Oncology, Daiichi Sankyo Inc, Dendreon Pharmaceuticals Inc, Eisai Inc, EMD Serono Inc, Exelixis Inc, Foundation Medicine, Genentech, a member of the Roche Group, Genmab, Genomic Health Inc, Gilead Sciences Inc, GlaxoSmithKline, Grail Inc, Guardant Health, Halozyme Inc, Helsinn Healthcare SA, ImmunoGenInc, Incyte Corporation, Infinity Pharmaceuticals Inc, Ipsen Biopharmaceuticals Inc, Janssen Biotech Inc, administered by Janssen Scientific Affairs LLC, Jazz Pharmaceuticals Inc, Kite, A Gilead Company, Lexicon Pharmaceuticals Inc, Lilly, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company, Merck, Merrimack Pharmaceuticals Inc, Myriad Genetic Laboratories Inc, Natera Inc, Novartis, Oncopeptides, Pfizer Inc, Pharmacyclics LLC, an AbbVie Company, Prometheus Laboratories Inc, Puma Biotechnology Inc, Regeneron Pharmaceuticals Inc, Sandoz Inc, a Novartis Division, Sanofi Genzyme, Seattle Genetics, SirtexMedical Ltd, Spectrum Pharmaceuticals Inc, Sumitomo Dainippon Pharma Oncology Inc, Taiho Oncology Inc, Takeda Oncology, Tesaro, A GSK Company, Teva Oncology, Tokai Pharmaceuticals Inc and Verastem Inc.

Research To Practice CME Planning Committee Members, Staff and Reviewers

Planners, scientific staff and independent reviewers for Research To Practice have no relevant conflicts of interest to disclose.

Prof Mok — Disclosures

Advisory Committee

AbbVie Inc, ACEA Pharma, Amgen Inc, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Blueprint Medicines, Boehringer Ingelheim Pharmaceuticals Inc, Bristol-Myers Squibb Company, Celgene Corporation, Cirina, CStone Pharmaceuticals, Daiichi Sankyo Inc, Fishawack Facilitate Ltd, G1 Therapeutics, Gritstone Oncology, Guardant Health, geneDecode Co Ltd, Hengrui Therapeutics Inc, Hutchison China MediTech Limited, Ignyta Inc, Incyte Corporation, IQVIA, Janssen Biotech Inc, Lilly, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company, Lunit Inc, Merck Serono, Merck Sharp & Dohme Corp, Mirati Therapeutics, Novartis, OncoGenex Pharmaceuticals Inc, OrigiMed, Pfizer Inc, Puma Biotechnology Inc, Roche Laboratories Inc, Sanofi-Aventis R&D, SFJ Pharmaceuticals, Takeda Oncology, Vertex Pharmaceuticals, Virtus Medical Group, Yuhan Corporation

Consulting Agreements

AbbVie Inc, ACEA Pharma, Alpha Biopharma, Amgen Inc, Amoy Diagnostics Co Ltd, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Blueprint Medicines, Boehringer Ingelheim Pharmaceuticals Inc, Bristol-Myers Squibb Company, Celgene Corporation, CStone Pharmaceuticals, Daiichi Sankyo Inc, Fishawack Facilitate Ltd, Gritstone Oncology, Guardant Health, Hengrui Therapeutics Inc, IgnytaInc, Incyte Corporation, IQVIA, INMED, Janssen Biotech Inc, Lilly, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company, Lunit Inc, Merck Serono, Merck Sharp & Dohme Corp, Mirati Therapeutics, Novartis, OncoGenex Pharmaceuticals Inc, OrigiMed, Pfizer Inc, Puma Biotechnology Inc, Roche Laboratories Inc, Sanofi-Aventis R&D, SFJ Pharmaceuticals, Takeda Oncology, Vertex Pharmaceuticals, Virtus Medical Group, Yuhan Corporation

Contracted Research

AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb Company, Clovis Oncology, G1 Therapeutics, Merck Serono, Merck Sharp & Dohme Corp, Novartis, Pfizer Inc, Roche Laboratories Inc, SFJ Pharmaceuticals, Takeda Oncology, Xcovery

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Upcoming Live Webinars

Meet The Professor: Management of Chronic Lymphocytic Leukemia

Wednesday, October 7, 202012:00 PM – 1:00 PM ET

ModeratorNeil Love, MD

FacultyMitchell R Smith, MD, PhD

Meet The Professor: Immunotherapy and Novel Agents in Gynecologic Cancers

Thursday, October 8, 202012:00 PM – 1:00 PM ET


FacultyBrian M Slomovitz, MD


Meet The Professor: Management of Chronic Lymphocytic Leukemia



FacultyJohn M Pagel, MD, PhD

Meet The Professor: Management of Ovarian Cancer



FacultyKathleen Moore, MD


Addressing Current Questions and Controversies in the Management of Non-Small Cell Lung Cancer with EGFR Mutation

Friday, October 16, 202011:00 AM – 12:00 PM ET


FacultyRoy S Herbst, MD, PhDSuresh S Ramalingam, MDHelena Yu, MD

Thank you for joining us!

CME and MOC credit information will be emailed to each participant within 5 days.

Meet The Professor Program Participating FacultyJohn V Heymach, MD, PhDProfessor and ChairThoracic/Head and Neck Medical OncologyThe University of Texas MD Anderson Cancer CenterHouston, Texas

Leora Horn, MD, MScIngram Associate Professor of Cancer ResearchDirector, Thoracic Oncology Research ProgramAssistant Vice Chairman for Faculty DevelopmentVanderbilt University Medical CenterNashville, Tennessee

Corey J Langer, MDDirector of Thoracic OncologyAbramson Cancer CenterProfessor of MedicinePerelman School of MedicineUniversity of PennsylvaniaPhiladelphia, Pennsylvania

Benjamin Levy, MD Associate ProfessorJohns Hopkins School of MedicineClinical DirectorMedical Director, Thoracic Oncology ProgramJohns Hopkins Sidney Kimmel Cancer Centerat Sibley MemorialWashington, DC

Professor Tony SK Mok, MDChairman, Department of Clinical OncologyThe Chinese University of Hong KongHong Kong, China

Meet The Professor Program Participating Faculty

Nathan A Pennell, MD, PhDProfessor, Hematology and Medical OncologyCleveland Clinic Lerner College of Medicine of Case Western Reserve UniversityDirector, Cleveland Clinic Lung Cancer Medical Oncology ProgramCleveland, Ohio

Lecia V Sequist, MD, MPHDirector, Center for Innovation in Early Cancer DetectionMassachusetts General Hospital Cancer CenterThe Landry Family Professor of MedicineHarvard Medical SchoolBoston, Massachusetts

Joel W Neal, MD, PhDAssociate Professor of MedicineDivision of OncologyDepartment of MedicineStanford Cancer InstituteStanford UniversityPalo Alto, California

David R Spigel, MDChief Scientific OfficerProgram DirectorLung Cancer Research Sarah Cannon Research InstituteNashville, Tennessee

Project ChairNeil Love, MDResearch To PracticeMiami, Florida

We Encourage Clinicians in Practice to Submit Questions

You may submit questions using the Zoom Chat

option below

Feel free to submit questions now before the program begins and throughout the program.

Familiarizing Yourself with the Zoom InterfaceHow to answer poll questions

When a poll question pops up, click your answer choice from the available options. Results will be shown after everyone has answered.

Meet The ProfessorManagement of Chronic Lymphocytic Leukemia


Mitchell R Smith, MD, PhD


Faculty

Meet The ProfessorImmunotherapy and Novel Agents

in Gynecologic CancersThursday, October 8, 2020

12:00 PM – 1:00 PM ET


Faculty Brian M Slomovitz, MD



John M Pagel, MD, PhD


Faculty

Meet The ProfessorManagement of Ovarian Cancer


Kathleen Moore, MD


Faculty

Addressing Current Questions and Controversies in the Management of

Non-Small Cell Lung Cancer with EGFR MutationFriday, October 16, 202011:00 AM – 12:00 PM ET

Roy S Herbst, MD, PhDSuresh S Ramalingam, MD

Helena Yu, MD


Faculty

Gigi Chen, MDDiablo Valley Oncology and Hematology Medical GroupPleasant Hill, California

Laurie Matt-Amaral, MD, MPHAttending PhysicianCleveland Clinic Akron General Medical CenterAkron, Ohio

Meet The Professor with Prof Mok

Module 1: Cases from Drs Matt-Amaral and Chen• Dr Matt-Amaral: A 49-year-old woman, nonsmoker with metastatic adenocarcinoma of the lung – PD-L1: 80%

• Dr Chen: A 72-year-old Asian woman with metastatic NSCLC – History of severe RA, on adalimumab; PD-L1: 50%

• Dr Matt-Amaral: A 66-year-old man with metastatic NSCLC – PD-L1: >50%

• Dr Chen: A 57-year-old man, never smoker with metastatic adenocarcinoma of the lung – Del(19) EGFR mutation

• Questions and Comments: Osimertinib resistance mutations; continued osimertinib in patients with brain metastases

• Dr Matt-Amaral: An 84-year-old man with NSCLC and brain metastases – PD-L1: 1%

• Questions and Comments: Clinical implications of the adjuvant osimertinib ADAURA trial

Module 2: Lung Cancer Journal Club with Prof Mok

Module 3: Beyond the Guidelines – Clinical Investigator Approaches to Common Clinical Scenarios

Module 4: Key Papers and Recent Approvals

Case Presentation – Dr Matt-Amaral: A 49-year-old woman, nonsmoker with metastatic adenocarcinoma of the lung – PD-L1: 80%

• Presented to the hospital with hand coordination difficulties

• Two brain masses (see images) and RLL mass identified

• Stage IV adenocarcinoma of the lung, EGFR and ALK: Wildtype, PD-L1: 80%

• Gamma Knife x 2

• Pembrolizumab x 16 à PD à Carboplatin/pemetrexed x 6 à Maintenance pemetrexed x 8 à PD

• Currently, carboplatin/gemcitabine x 9, and ongoing

Questions

• In light of her progressive disease, should we re-run an NGS panel? Would it be reasonable to re-biopsy her?

Dr Laurie Matt-Amaral

Case Presentation – Dr Matt-Amaral: A 49-year-old woman –Brain Masses, with Edema

Case Presentation – Dr Chen: A 72-year-old Asian woman with metastatic NSCLC – History of severe RA, on adalimumab; PD-L1: 50%

• 4/2020: Diagnosed with Stage IV NSCLC, with extensive bony metastases• FoundationOne®: Positive for METD1010H, CDH1, CDKN2A, CDKN2B, MTAP and NF1

- PD-L1: 50%• Palliative RT to RUL, right clavicular bone lesion, right pelvis and femur• Crizotinib• Restaging scan: PD and 2 new small brain metastases

• Capmatinib 400 mg BID- Developing more lower extremity edema

Questions

• If she progresses or cannot tolerate the targeted therapy and also progresses on chemotherapy, would a checkpoint inhibitor be a good option for her?

Dr Gigi Chen

Case Presentation – Dr Matt-Amaral: A 66-year-old man with metastatic NSCLC – PD-L1: >50%

• Lung nodule identified during lung cancer screening (former smoker)

• Scans during surgery planning: Left humeral head lesion

• Biopsy: Metastatic disease, PD-L1 > 50%, no actionable mutations on hotspot panel

• Pembrolizumab x 4 à PD à Carboplatin/pemetrexed/pembrolizumab

• Currently, maintenance pemetrexed/pembrolizumab

Questions

• How would you have approached treatment of his oligometastatic disease?

• After disease progression on pembrolizumab, would you have added the chemotherapy, or stopped the pembrolizumab and continued with chemotherapy alone?


Case Presentation – Dr Matt-Amaral: A 66-year-old man

Lung Masses Bone Lesion

Case Presentation – Dr Chen: A 57-year-old man, never smoker with metastatic adenocarcinoma of the lung – Del(19) EGFR mutation

• Work up after skiing accident reveals metastatic adenocarcinoma of the lung- Involvement of the LUL, hilar and mediastinal adenopathy, liver, bone and brain- EGFR del19 mutation

• 8/2018: Osimertinib and zoledronic acid, with initial response systemically and in brain• One year later: PD in bone à SBRT à Zoledronic acid switched to denosumab (severe jaw pain)

- Reverted to zoledronic acid • Currently, scans show multiple new bone progressions, lung disease is stable• GUARDANT: Predominant EGFR exon 19, but also has small amount of EGFR C797s, BRAF V600E,

RET fusion and MET amplification, TP53 and RB1• Carboplatin/pemetrexed

Questions• How would you manage the denosumab-associated jaw pain? Would you have switched back to

zoledronic acid?

Dr Gigi Chen

Osimertinib Adjuvant Therapy in Patients (pts) with Resected EGFR Mutated (EGFRm) NSCLC (ADAURA): Central Nervous System (CNS) Disease RecurrenceTsuboi M et al.ESMO 2020;Abstract LBA1.

ADAURA: Sites of Disease Recurrence

Tsuboi M et al. ESMO 2020;Abstract LBA1.

ADAURA: CNS DFS Events


ADAURA: CNS DFS in Overall Population


Questions and Comments: Osimertinib resistance mutations; continued osimertinib in patients with brain metastases

Dr Gigi Chen

Case Presentation – Dr Matt-Amaral: An 84-year-old man with NSCLC and brain metastases – PD-L1: 1%

• Diagnosed with separate LLL and RUL adenocarcinoma lung primaries- PET and bronchoscopy negative for LAD, PD-L1: 1%

• SBRT to both primaries à Observation

• Approximately 1 year later, developed unsteady gait, headaches

• MRI: Multiple brain metastases (largest 3.5-cm)- Gamma Knife x 2

• Carboplatin/pemetrexed/pembrolizumab x 4 à maintenance therapy

Questions

• Would you have treated this patient differently? Instead of SBRT, would you have pushed harder for systemic therapy? Or, due to his age, do you believe radiation therapy was sufficient?


Questions and Comments: Clinical implications of the adjuvant osimertinib ADAURA trial

Dr Gigi Chen

Osimertinib as Adjuvant Therapy in Patients (pts) with Stage IB–IIIA EGFR Mutation Positive (EGFRm) NSCLC After Complete Tumor Resection: ADAURAHerbst RS et al.ASCO 2020;Abstract LBA5.

Discussion of LBA5Discussant: David R Spigel, MD, FASCO | Sarah Cannon Research Institute

ADAURA Phase III Trial Schema

Herbst RS et al. ASCO 2020;Abstract LBA5.

ADAURA Primary Endpoint: Inv-Assessed DFS(Stage II/IIIA)


ADAURA: DFS by Stage


ADAURA Secondary Endpoint: Inv-Assessed DFS in the Overall Population (Stage IB/II/IIIA)


Meet The Professor with Prof MokModule 1: Cases from Drs Chen and Matt-Amaral

Module 2: Lung Cancer Journal Club with Prof Mok• Timeline of systemic therapy advances in NSCLC• Challenges and opportunities of cfDNA analysis implementation in clinical practice• Osimertinib for leptomeningeal metastases• ATOM study of preemptive local ablative therapy to residual oligometastases of NSCLC after EGFR TKI • ALTA-1L trial of brigatinib versus crizotinib for advanced ALK inhibitor-naïve ALK-positive NSCLC• CROWN study of lorlatinib versus crizotinib for advanced ALK inhibitor-naïve ALK-positive NSCLC• Impact of MET inhibitors on survival in NSCLC with MET exon 14 mutations• Asian expert consensus statement on optimal management of Stage III NSCLC • Atezolizumab/bevacizumab/chemotherapy – Subgroup analysis of the IMpower150 trial for patients with EGFR mutations• Relationship between STK11 and KEAP1 mutational status and first-line pembrolizumab efficacy in KEYNOTE-042 • Impact of smoking on the effectiveness of immune checkpoint inhibitors • Pattern and impact of hepatic adverse events with immune checkpoint inhibitors • Safety and feasibility of CRISPR-edited T cells for patients with refractory NSCLC • Acupuncture in the management of chemotherapy-induced peripheral neuropathy



Ang MK, Mok TSK. Respirology 2020;25(1):26-31.

Timeline of the Development of Systemic Therapy in Advanced NSCLC

Ang MK, Mok TSK. Respirology 2020;25(1):26-31.

Crizotinib approved

Liquid Biopsies: Underlying Biology of Nucleic Acid Content Shedding, Detection and Practical Clinical Utility

Rolfo C et al; ISLB. Crit Rev Oncol Hematol 2020;151:102978.

Application of Circulating Biomarkers (Liquid Biopsy)

Rolfo C, et al; ISLB. Crit Rev Oncol Hematol 2020;151:102978.

Application of blood-based liquid biopsy analysis over the span of lung, breast and colorectal cancer. Blood is collected periodically for isolation of circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) and exosomes/organoids. These circulating biomarkers may be applied to guide initial diagnosis, treatment monitoring or planning, prognosis prediction and developing a sequential targeted therapy for patients with diverse solid tumors.

J Thorac Oncol 2020;15(4):637-48.

J Clin Oncol 2020;[Online ahead of print]

J Clin Oncol 2020;[Online ahead of print]

Solomon B et al. ESMO 2020;Abstract LBA2.

Lorlatinib vs Crizotinib in the First-Line Treatment of Patients (pts) with Advanced ALK-Positive Non-Small Cell Lung Cancer (NSCLC): Results of the Phase III CROWN Study

J Thorac Oncol 2020;15(3):324-43

Lancet Respir Med 2019;7(5):387-401

Cho BC et al. AACR 2020;Abstract CT084.

Relationship between STK11 and KEAP1 Mutational Status and Efficacy in KEYNOTE-042: Pembrolizumab Monotherapy versus Platinum-Based Chemotherapy as First-Line Therapy for PD-L1-Positive Advanced NSCLC

Acta Oncol 2020;59(1):96-100.

Cancer Med 2020;[Online ahead of print]

Nat Med 2020;26(5):732-40

Acupunct Med 2020;[Online ahead of print]

Molassiotis A1, Dawkins B2, Longo R2, Suen LKP1, Cheng HL1, Mok T3, HulmeC2, Yeo W3.

Regulatory and reimbursement issues aside, which adjuvant systemic therapy would you generally recommend for a patient with Stage IIBnonsquamous NSCLC and an EGFR exon 19 deletion?

1. Chemotherapy 2. Osimertinib3. Chemotherapy followed by osimertinib4. Other

Pembro/carbo/pem

Pembro/carbo/pem

Pembro/carbo/pem

Pembro/carbo/pem

Pembro/carbo/pem

Pembro

Pembro or hospice

Pembro

Pembro

Pembro/carbo/pem†

Pembro

Pembro

Pembro

Pembro +/- carbo/pem

Pembro

Pembro

Pembro

Pembro

Pembro

Pembro

Age 65 Age 80 Age 65 Age 80

TPS of 10% TPS of 60%

Pembro/carbo/pem Pembro/carbo/pem Pembro Pembro

Pembro/carbo/pem Pembro Pembro* Pembro

Pem = pemetrexed

* If very symptomatic, pembro/carbo/pem; † Likely dose-reduced chemotherapy

Which first-line treatment regimen would you recommend for a patient with metastatic nonsquamous lung cancer, no identified targetable mutations and a PD-L1 TPS of 10%? Of 60%?

Which first-line treatment regimen would you recommend for a patient with metastatic squamous lung cancer, no identified targetable mutations and a PD-L1 TPS of 10%? Of 60%?

Pembro/carbo/ nab-P

Pembro/carbo/ nab-P

Pembro/carbo/ nab-P

Pembro/carbo/ nab-P or P

Pembro/carbo/nab-P

Pembro

Pembro/carbo/nab-P

Pembro/carbo/P

Pembro/carbo/nab-P

Pembro/carbo/P

Pembro

Pembro

Pembro

Pembro +/- carbo/nab-P or P

Pembro

Pembro

Pembro

Pembro

Pembro+/- carbo/nab-P

Pembro

Age 65 Age 80 Age 65 Age 80

TPS of 10% TPS of 60%

Pembro/carbo/nab-P Pembro/carbo/nab-P Pembro Pembro

Pembro/carbo/nab-P Pembro/carbo/nab-P Pembro Pembro

Nab-P = nanoparticle albumin-bound paclitaxel; P = paclitaxel

2 years

2 years

Indefinitely or until PD/toxicity

2 years

2 years


2 years


2 years

2 years

Complete clinical response Partial clinical response

Likely 2 years but CR duration dependent Indefinitely or until PD/toxicity

2 years (min) 2 years (min)

PD = progressive disease

How long would you continue treatment for a patient with metastatic NSCLC who is receiving an anti-PD-1/PD-L1 antibody and at first evaluation is tolerating it well and has a…

What is your preferred second-line treatment for a patient with extensive-stage small cell cancer of the lung with metastases and disease progression on chemotherapy/atezolizumab?

1. Topotecan or irinotecan2. Lurbinectedin3. Nivolumab/ipilimumab4. Pembrolizumab5. Nivolumab6. Other

Carbo/etoposide + atezolizumab








Carbo/etoposide + atezolizumab or durvalumab


Age 65 Age 80

Carbo/etoposide + durvalumab Carbo/etoposide + durvalumab

Carbo/etoposide + atezolizumabor durvalumab Carbo/etoposide + durvalumab

Regulatory and reimbursement issues aside, what would be your preferred first-line treatment regimen for a patient with extensive-stage SCLC?

Regulatory and reimbursement issues aside, what would be your preferred first-line treatment regimen for a 65-year-old patient with extensive-stage SCLC and neurologic paraneoplastic syndrome causing moderate to severe proximal myopathy?

Carboplatin/etoposide



Carboplatin/etoposide + atezolizumab or durvalumab


Carboplatin/etoposide + durvalumab


Regulatory and reimbursement issues aside, what would be your preferred first-line treatment for a 65-year-old patient with extensive-stage SCLC and symptomatic SIADH, in addition to standard treatment for SIADH?


Carboplatin/etoposide/atezolizumab




Carboplatin/etoposide + durvalumab


SIADH = syndrome of inappropriate antidiuretic hormone secretion

Accelerated Approval of Lurbinectedin for Metastatic SCLCPress Release – June 15, 2020

“On June 15, 2020, the Food and Drug Administration granted accelerated approval to lurbinectedin for adult patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy.

Efficacy was demonstrated in the PM1183-B-005-14 trial (Study B-005; NCT02454972), a multicenter open-label, multi-cohort study enrolling 105 patients with metastatic SCLC who had disease progression on or after platinum-based chemotherapy. Patients received lurbinectedin 3.2 mg/m2 by intravenous infusion every 21 days until disease progression or unacceptable toxicity.

The recommended lurbinectedin dose is 3.2 mg/m2 every 21 days.”

https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-lurbinectedin-metastatic-small-cell-lung-cancer.

FDA Grants Approval of Pralsetinib for the Treatment of Metastatic NSCLC with RET FusionPress Release – September 7, 2020

“The Food and Drug Administration has approved pralsetinib for the treatment of adults with metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA approved test. This indication was approved under the FDA’s Accelerated Approval programme, based on data from the phase I/II ARROW study. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Pralsetinib is a once-daily, oral precision therapy designed to selectively target RET alterations, including fusions and mutations.

The approval is based on the results from the phase I/II ARROW study, in which pralsetinib produced durable clinical responses in people with RET fusion-positive NSCLC with or without prior therapy, and regardless of RET fusion partner or central nervous system involvement. Pralsetinibdemonstrated an overall response rate (ORR) of 57% ... and complete response (CR) rate of 5.7% in the 87 people with NSCLC previously treated with platinum-based chemotherapy. In the 27 people with treatment-naïve NSCLC, the ORR was 70%, with an 11% CR rate.”

https://www.globenewswire.com/news-release/2020/09/07/2089388/0/en/Roche-announces-FDA-approval-of-Gavreto-pralsetinib-for-the-treatment-of-adults-with-metastatic-RET-fusion-positive-non-small-cell-lung-cancer.html

FDA Approves Selpercatinib for Lung and Thyroid Cancer with RET Gene Mutations or FusionsPress Release — May 8, 2020

“On May 8, 2020, the Food and Drug Administration granted accelerated approval to selpercatinib for the following indications:

• Adult patients with metastatic RET fusion-positive non-small cell lung cancer (NSCLC);

• Adult and pediatric patients ≥12 years of age with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy;

• Adult and pediatric patients ≥12 years of age with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate).

Efficacy was investigated in a multicenter, open-label, multi-cohort clinical trial (LIBRETTO-001) in patients whose tumors had RET alterations.”

https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-selpercatinib-lung-and-thyroid-cancers-ret-gene-mutations-or-fusions

FDA Grants Accelerated Approval to Capmatinib for Metastatic Non-Small Cell Lung CancerPress Release — May 6, 2020

“On May 6, 2020, the Food and Drug Administration granted accelerated approval to capmatinib for adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have a mutation that leads to mesenchymal-epithelial transition (MET) exon 14 skipping as detected by an FDA-approved test.

The FDA also approved the FoundationOne CDx assay as a companion diagnostic for capmatinib.

Efficacy was demonstrated in the GEOMETRY mono-1 trial (NCT02414139), a multicenter, non-randomized, open-label, multicohort study enrolling 97 patients with metastatic NSCLC with confirmed MET exon 14 skipping.

The recommended capmatinib dose is 400 mg orally twice daily with or without food.”

https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-capmatinib-metastatic-non-small-cell-lung-cancer

Trastuzumab Deruxtecan (T-DXd; DS-8201) in Patients with HER2-Mutated Metastatic Non-Small Cell Lung Cancer (NSCLC): Interim Results of DESTINY-Lung01

Smit EF et al.ASCO 2020;Abstract 9504.

Antibody-Drug Conjugate Trastuzumab Deruxtecan

Smit EF et al. Proc ASCO 2020;Abstract 9504.

DESTINY-Lung01: Efficacy


Confirmed ORR (by ICR) = 61.9%DCR = 90.5%Median DoR = not reached

• Median PFS = 14.0 mos

DESTINY-Lung01: Treatment-Emergent AEs


DESTINY-Lung01: AEs of Special Interest – Interstitial Lung Disease




Mitchell R Smith, MD, PhD


Faculty

Thank you for joining us!

CME and MOC credit information will be emailed to each participant within 5 days.

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