1 september 2023: zie ook dit artikel: https://kanker-actueel.nl/pirtobrutinib-een-niet-covalente-btk-remmer-blijkt-effectief-bij-zwaar-voorbehandelde-patienten-met-chronische-lymfatische-leukemie-cll-of-kleincellig-lymfatisch-lymfoom-sll-die-eerder-een-covalente-btk-remmer-hadden-gehad.html

1 september 2023: Bron: FDA en Clin Cancer Res CCR-23-1272. 25 augustus 2023

De Food and Drug Administration (FDA) geeft versnelde goedkeuring aan pirtobrutinib (Jaypirca)  een zogeheten BTK-remmer, voor patiënten met een zwaar voorbehandelde recidiverend of refractair mantelcellymfoom (MCL) na ten minste twee lijnen systemische therapie (chemokuren), plus een andere BTK-remmer dan pirtobrutinib (Jaypirca)

De FDA baseerde deze versnelde toestemming op basis van de resultaten uit de BRUIN-studie, een open-label, multicenter, eenarmige studie met pirtobrutinib als monotherapie waaraan 120 patiënten met mantelcellymfoom (MCL) deelnamen die eerder waren behandeld met een andere BTK-remmer.

Deelnemende patiënten hadden gemiddeld drie eerdere behandelingen gehad, waarbij 93% twee of meer eerdere behandelingen had gehad. De deelnemende patiënten warden dus zwaar voorbehandeld.

De meest voorkomende eerder ontvangen BTK-remmers waren ibrutinib (67%), acalabrutinib (30%) en zanubrutinib (8%); 83% was gestopt met hun laatste BTK-remmer vanwege een refractaire of progressieve ziekte. 
Pirtobrutinib (Jaypirca) werd oraal toegediend in een dosis van 200 mg eenmaal daags en werd voortgezet tot ziekteprogressie of onaanvaardbare toxiciteit zich zou voordoen.

De belangrijkste doelen van de studie waren het algehele responspercentage (ORR) en de duur van de respons (DOR), zoals beoordeeld door een onafhankelijke beoordelingscommissie op basis van de criteria van Lugano.

Het algehele responspercentage (ORR) was 50% (95% BI: 41, 59) met een CR = compleet remissie percentage van 13%. De geschatte mediane duur van de respons (DOR) was 8,3 maanden (95%-BI: 5,7, NE) en de geschatte duur van de respons (DOR)-percentage na 6 maanden was 65,3% (95%-BI: 49,8; 77,1).

De meest voorkomende bijwerkingen (≥15%) bij patiënten met mantelcellymfoom (MCL) waren vermoeidheid, pijn aan het bewegingsapparaat, diarree, oedeem, kortademigheid, longontsteking en blauwe plekken.
Graad 3 of 4 laboratoriumafwijkingen bij ≥10% van de patiënten waren een verlaagd aantal neutrofielen, lymfocyten en bloedplaatjes.

De publicatie van de BRUIN-studie over pirtobrutinib (Jaypirca)  bij mantelcellymfoom (MCL) is het volledige studierapport gratis in te zien. 

 2023 Aug 20; 41(24): 3988–3997.
Published online 2023 May 16. doi: 10.1200/JCO.23.00562
PMCID: PMC10461952
PMID: 37192437

Pirtobrutinib in Covalent Bruton Tyrosine Kinase Inhibitor Pretreated Mantle-Cell Lymphoma

Michael L. Wang, MD,corresponding author 1 Wojciech Jurczak, MD, PhD, 2 Pier Luigi Zinzani, MD, PhD, 3 , 4 Toby A. Eyre, MD, MBChB, DipMedEd, MRCP, FRCPath, 5 Chan Y. Cheah, MD, 6 , 7 Chaitra S. Ujjani, MD, 8 Youngil Koh, MD, 9 Koji Izutsu, MD, PhD, 10 James N. Gerson, MD, 11 Ian Flinn, MD, PhD, 12 Benoit Tessoulin, MD, 13 Alvaro J. Alencar, MD, 14 Shuo Ma, MD, PhD, 15 David Lewis, PhD, MBChB, 16 Ewa Lech-Maranda, MD, PhD, 17 Joanna Rhodes, MD, 18 , 19 Krish Patel, MD, 20 Kami Maddocks, MD, 21 Nicole Lamanna, MD, 22 Yucai Wang, MD, PhD,corresponding author 23 Constantine S. Tam, MD, 24 Talha Munir, MBBS, 25 Hirokazu Nagai, MD, PhD, 26 Francisco Hernandez-Ilizaliturri, MD, 27 Anita Kumar, MD, 28 Timothy S. Fenske, MD, MS, 29 John F. Seymour, PhD, MBBS, FRACP, 24 Andrew D. Zelenetz, MD, PhD, 28 Binoj Nair, PhD, 30 Donald E. Tsai, MD, PhD, 30 Minna Balbas, PhD, 30 Richard A. Walgren, MD, PhD, 30 Paolo Abada, MD, PhD, 30 Chunxiao Wang, PhD,corresponding author 31 Junjie Zhao, PhD, 30 Anthony R. Mato, MD, MSCE, 28 and Nirav N. Shah, MD 29



Pirtobrutinib is a highly selective, noncovalent (reversible) Bruton tyrosine kinase inhibitor (BTKi). We report the safety and efficacy of pirtobrutinib in patients with covalent Bruton tyrosine kinase inhibitor (cBTKi) pretreated mantle-cell lymphoma (MCL), a population with poor prognosis.


Patients with cBTKi pretreated relapsed/refractory (R/R) MCL received pirtobrutinib monotherapy in a multicenter phase I/II trial (BRUIN; ClinicalTrials.gov identifier: NCT03740529). Efficacy was assessed in the first 90 consecutively enrolled patients who met criteria for inclusion in the primary efficacy cohort. The primary end point was overall response rate (ORR). Secondary end points included duration of response (DOR) and safety.


The median patient age was 70 years (range, 46-87), the median prior lines of therapy was 3 (range, 1-8), 82.2% had discontinued a prior cBTKi because of disease progression, and 77.8% had intermediate- or high-risk simplified MCL International Prognostic Index score. The ORR was 57.8% (95% CI, 46.9 to 68.1), including 20.0% complete responses (n = 18). At a median follow-up of 12 months, the median DOR was 21.6 months (95% CI, 7.5 to not reached). The 6- and 12-month estimated DOR rates were 73.6% and 57.1%, respectively. In the MCL safety cohort (n = 164), the most common treatment-emergent adverse events (TEAEs) were fatigue (29.9%), diarrhea (21.3%), and dyspnea (16.5%). Grade ≥3 TEAEs of hemorrhage (3.7%) and atrial fibrillation/flutter (1.2%) were less common. Only 3% of patients discontinued pirtobrutinib because of a treatment-related adverse event.


Pirtobrutinib is a first-in-class novel noncovalent (reversible) BTKi and the first BTKi of any kind to demonstrate durable efficacy after prior cBTKi therapy in heavily pretreated R/R MCL. Pirtobrutinib was well tolerated with low rates of treatment discontinuation because of toxicity.


  • Key Objective
  • Despite the efficacy of covalent Bruton tyrosine kinase inhibitors (cBTKi) in mantle-cell lymphoma (MCL), resistance invariably develops. Treatment options are then limited, and consequently, patient outcomes are poor with a median overall survival of <10 months. Pirtobrutinib, a highly selective, noncovalent (reversible) Bruton tyrosine kinase inhibitor (BTKi), inhibits both wild-type and C481-mutant Bruton tyrosine kinase (BTK) with equal low nM potency and has favorable oral pharmacology that enables continuous BTK inhibition throughout the daily dosing interval, regardless of intrinsic rate of BTK turnover. Here, we report the safety and efficacy of pirtobrutinib in patients with cBTKi pretreated MCL.
  • Knowledge Generated
  • Pirtobrutinib is a first-in-class noncovalent (reversible) BTKi, and the first BTKi of any kind to demonstrate durable efficacy after prior cBTKi therapy in heavily pretreated patients with relapsed/refractory MCL. Pirtobrutinib was well tolerated with low rates of cBTKi-associated adverse events and discontinuation because of drug-related toxicity.
  • Relevance (J.W. Friedberg)
  • These data directly inform the regulatory approval of pirtobrutinib for patients with MCL, and provide rationale for planned and ongoing phase III studies comparing covalent to non-covalent BTKi in several hematological malignancies.*

    *Relevance section written by JCO Editor-in-Chief Jonathan W. Friedberg, MD.


We thank the BRUIN clinical trial participants and their caregivers, without whom this work would not be possible. We also thank the BRUIN trial investigators and study staff. Garreth Lawrence PhD, employee of Eli Lilly and Company, provided medical writing support.

Conflict of interest statement

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.

Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).

Michael L. Wang

Honoraria: Janssen Research & Development, Dava Oncology, AstraZeneca, Cahon, Acerta Pharma, BeiGene, Kite, a Gilead company, Moffit Cancer Center, Physicans' Education Resource, Breast-Gynecological International Cancer Society, Pharmacyclics/Janssen, Eastern Virginia Medical School, Leukemia and Lymphoma Society, Medscape, Meeting Minds Experts, OncLive/MJH Life Sciences, Practice Point Communications, Bioinvent, AbbVie, Bantam Pharmaceutical, Bristol Myers Squibb Foundation, Genmab, IDEOlogy Health, MD Education, Merck, Nurix, Oncology Specialty Group, Studio ER Congressi

Consulting or Advisory Role: AstraZeneca, Janssen Research & Development, Bioinvent, Pharmacyclics/Janssen, Kite, a Gilead company, Innocare, Oncternal Therapeutics, Genentech, BeiGene, DTRM, Miltenyi Biomedicine, VelosBio, Deciphera, Lilly, Pepromene, AbbVie, Acerta Pharma, ADC Therapeutics, Amphista Therapeutics, Be Biopharma, Leukemia and Lymphoma Society, Merck, Milken Institute, Parexel

Research Funding: AstraZeneca, Janssen Research & Development, Pharmacyclics, Kite, a Gilead company, Juno Therapeutics, BeiGene, Acerta Pharma, Oncternal Therapeutics, Bioinvent, Loxo, VelosBio, Celgene, Molecular Templates, Lilly, Innocare, Genmab, Genentech, Vincerx Pharma

Travel, Accommodations, Expenses: AstraZeneca, Celgene, Dava Oncology, Kite, a Gilead company, Physicans' Education Resource

Wojciech Jurczak

Consulting or Advisory Role: BeiGene, AstraZeneca, Lilly

Research Funding: Roche, Takeda, Janssen-Cilag, BeiGene, Morphosys, AstraZeneca, Lilly

Pier Luigi Zinzani

Consulting or Advisory Role: Celltrion, Gilead Sciences, Janssen-Cilag, Bristol Myers Squibb, Servier, Sandoz, MSD, Roche, EUSA Pharma, Kyowa Hakko Kirin, Takeda, Secura Bio, TG Therapeutics, Novartis, ADC Therapeutics, Incyte, BeiGene

Speakers' Bureau: MSD, EUSA Pharma, Novartis

Toby A. Eyre

Honoraria: Roche, Gilead Sciences, Janssen Oncology, AbbVie, AstraZeneca/MedImmune, Loxo/Lilly, Incyte, Secura Bio, Autolus Therapeutics

Consulting or Advisory Role: Roche, Kite/Gilead, AbbVie, AstraZeneca/MedImmune, Loxo, BeiGene, Incyte, Secura Bio

Research Funding: AstraZeneca/MedImmune, BeiGene

Chan Y. Cheah

Honoraria: Roche/Genentech, Janssen-Cilag, TG Therapeutics, Loxo/Lilly, AstraZeneca, Bristol Myers Squibb, Gilead Sciences, BeiGene, Novartis

Consulting or Advisory Role: Janssen-Cilag, Roche/Genentech (Inst), TG Therapeutics, Loxo/Lilly, Gilead Sciences, AstraZeneca, Bristol Myers Squibb, Ascentage Pharma, Merck

Research Funding: Roche/Genentech (Inst), Bristol Myers Squibb (Inst), AbbVie (Inst), Merck (Inst)

Travel, Accommodations, Expenses: Roche

Chaitra S. Ujjani

Honoraria: Pharmacyclics, AbbVie, Genentech, Janssen, Incyte, BeiGene, Lilly

Consulting or Advisory Role: AstraZeneca, Epizyme, Atara Biotherapeutics

Research Funding: Pharmacyclics (Inst), AbbVie (Inst), Lilly, AstraZeneca/MedImmune, Adaptive Biotechnologies, Kite, a Gilead company

Youngil Koh

Leadership: GenomeOpinion

Stock and Other Ownership Interests: Curocell

Honoraria: Janssen, Amgen, Novartis, Takeda Korea

Consulting or Advisory Role: Prothena

Koji Izutsu

Honoraria: Takeda, Chugai Pharma, Eisai, Janssen, AbbVie, Novartis, MSD, Dainippon Sumitomo Pharma, Ono Pharmaceutical, Mundipharma, HUYA Bioscience International, AstraZeneca, Bayer, Bristol Myers Squibb, Kyowa Kirin, Fujifilm, Celgene, Daiichi Sankyo, Allergan, SymBio Pharmaceuticals, Pfizer, Meiji Seika Kaisha, Nippon Kayaku, Lilly

Consulting or Advisory Role: Bayer, Celgene, AstraZeneca, Ono Pharmaceutical, Kyowa Kirin, AbbVie, Genmab, Bristol Myers Squibb, Nippon Shinyaku, Mitsubishi Tanabe Pharma

Research Funding: Eisai, Chugai Pharma

James N. Gerson

Research Funding: Loxo

Ian Flinn

Consulting or Advisory Role: AbbVie (Inst), TG Therapeutics (Inst), Kite, a Gilead company (Inst), BeiGene (Inst), Genentech (Inst), Novartis (Inst), Century Therapeutics (Inst), Hutchison MediPharma (Inst), Servier (Inst), Vincerx Pharma (Inst), Genmab (Inst), Innocare (Inst), Myeloid Therapeutics (Inst), Secura Bio (Inst), Xencor (Inst)

Research Funding: Acerta Pharma (Inst), Agios (Inst), Celgene (Inst), Constellation Pharmaceuticals (Inst), Genentech (Inst), Gilead Sciences (Inst), Incyte (Inst), Infinity Pharmaceuticals (Inst), Janssen (Inst), Kite, a Gilead company (Inst), Novartis (Inst), Pharmacyclics (Inst), Portola Pharmaceuticals (Inst), Roche (Inst), TG Therapeutics (Inst), Trillium Therapeutics (Inst), AbbVie (Inst), ArQule (Inst), BeiGene (Inst), Curis (Inst), Forma Therapeutics (Inst), Forty Seven (Inst), Merck (Inst), Pfizer (Inst), Verastem (Inst), AstraZeneca (Inst), Unum Therapeutics (Inst), MorphoSys (Inst), Seagen (Inst), IGM Biosciences (Inst), Loxo (Inst), Rhizen Pharmaceuticals (Inst), Triact Therapeutics (Inst), Bristol Myers Squibb (Inst), CALGB (Inst), CTI (Inst), Fate Therapeutics (Inst), Millennium (Inst), Tessa Therapeutics (Inst), City of Hope (Inst), CALIBR (Inst), Bio-Path Holdings, Inc (Inst), Nurix (Inst), Innocare (Inst), Myeloid Therapeutics (Inst), Epizyme (Inst), Marker Therapeutics (Inst), Step Pharma (Inst), Vincerx Pharma (Inst), 2seventy bio (Inst)

Benoit Tessoulin

Honoraria: Kite/Gilead, AbbVie

Travel, Accommodations, Expenses: Kite/Gilead, AbbVie

Alvaro J. Alencar

Consulting or Advisory Role: Kite, a Gilead company, Amgen, Karyopharm Therapeutics, Seagen, Epizyme, Janssen, BeiGene, Incyte, TG Therapeutics, Genentech, Dr Reddy's Laboratories, Lilly

Research Funding: Loxo

Open Payments Link: https://openpaymentsdata.cms.gov/physician/1171980

Shuo Ma

Consulting or Advisory Role: Genentech/Roche, AbbVie, Pharmacyclics, Janssen Oncology, AstraZeneca, BeiGene, Bristol Myers Squibb/Celgene/Juno, TG Therapeutics

Speakers' Bureau: Pharmacyclics, Janssen Oncology, AstraZeneca, BeiGene, Lilly

Research Funding: Pharmacyclics (Inst), AbbVie (Inst), BeiGene (Inst), Loxo/Lilly (Inst), Juno/Bristol-Myers Sqibb (Inst), AstraZeneca (Inst), IgM Biosciences (Inst)

David Lewis

Consulting or Advisory Role: Janssen Oncology, Kite/Gilead, BeiGene, AbbVie

Travel, Accommodations, Expenses: Kite, a Gilead company

Joanna Rhodes

Honoraria: Dava Oncology, Curio Science, Aptitude Health

Consulting or Advisory Role: AbbVie, Verastem, Genentech, Pharmacyclics, TG Therapeutics, SeaGen, Morphosys, Janssen, BeiGene, Genmab, Epizyme

Research Funding: Loxo/Lilly (Inst), Acerta Pharma (Inst), Pharmacyclics (Inst), Oncternal Therapeutics (Inst), VelosBio (Inst), Epizyme (Inst)

Travel, Accommodations, Expenses: DAVA Pharmaceuticals, Loxo, Curio Science

Krish Patel

Consulting or Advisory Role: AstraZeneca, Genentech, BeiGene, Pharmacyclics, Bristol Myers Squibb/Celgene/Juno, Morphosys, Kite, a Gilead company, TG Therapeutics, Loxo/Lilly, AbbVie, Seagen, Epizyme, ADC Therapeutics, Caribou Biosciences, Xencor, Fate Therapeutics

Speakers' Bureau: AstraZeneca, Bristol Myers Squibb/Celgene, Kite, a Gilead company, TG Therapeutics

Research Funding: AstraZeneca (Inst), Xencor (Inst), Pharmacyclics (Inst), Curis (Inst), Bristol Myers Squibb (Inst), Celgene (Inst), MEI Pharma (Inst), Trillium Therapeutics (Inst), Kite/Gilead (Inst), Roche/Genentech (Inst), Fate Therapeutics (Inst), Takeda (Inst), Epizyme (Inst), Aptevo Therapeutics (Inst), Nurix (Inst), Loxo/Lilly (Inst)

Kami Maddocks

Honoraria: Pharmacyclics, Celgene, Seagen, MorphoSys, BMS, Karyopharm Therapeutics, Kite, a Gilead company, ADC Therapeutics, Genmab, Lilly, Genentech, Epizyme, AstraZeneca/Merck, BeiGene, Incyte, AbbVie

Research Funding: Pharmacyclics, Merck, Bristol Myers Squibb

Nicole Lamanna

Consulting or Advisory Role: Celgene, Genentech, AbbVie, ProNAi, Pharmacyclics, Juno Therapeutics, Roche, Janssen, AstraZeneca, Gilead Sciences, BeiGene, Loxo/Lilly, Bristol Myers Squibb Foundation

Research Funding: Genentech/AbbVie (Inst), AbbVie (Inst), Infinity Pharmaceuticals (Inst), Gilead Sciences (Inst), ProNAi (Inst), Beigene (Inst), AstraZeneca (Inst), Verastem (Inst), Juno Therapeutics (Inst), TG Therapeutics (Inst), Acerta Pharma/AstraZeneca (Inst), Loxo (Inst), Oncternal Therapeutics, Inc (Inst), MingSight (Inst), Octapharm (Inst)

Yucai Wang

Employment: Merck

Stock and Other Ownership Interests: Merck

Honoraria: Kite, a Gilead company (Inst)

Consulting or Advisory Role: Loxo (Inst), Incyte (Inst), Innocare (Inst), TG Therapeutics (Inst), Kite, a Gilead company (Inst), Lilly (Inst), Janssen (Inst), BeiGene (Inst)

Research Funding: InnoCare (Inst), Incyte (Inst), Novartis (Inst), Genentech (Inst), Loxo (Inst), MorphoSys (Inst), Genmab (Inst)

Constantine S. Tam

Honoraria: Janssen-Cilag, AbbVie, Novartis, Beigene, Pharmacyclics, Roche/Genentech, Loxo/Lilly

Consulting or Advisory Role: Janssen, Loxo, Roche, BeiGene, AbbVie

Research Funding: Janssen-Cilag (Inst), AbbVie (Inst), BeiGene (Inst)

Talha Munir

Consulting or Advisory Role: Janssen-Cilag, AstraZeneca, BeiGene, Sobi, Roche, AbbVie, Alexion Pharmaceuticals, Lilly

Speakers' Bureau: AbbVie, Janssen-Cilag, Gilead Sciences, Alexion Pharmaceuticals, AstraZeneca, Sobi

Travel, Accommodations, Expenses: Janssen-Cilag, AbbVie, Alexion Pharmaceuticals, AstraZeneca

Hirokazu Nagai

Honoraria: Janssen, Ono Pharmaceutical, Bristol Myers Squibb, Chugai Pharma, Takeda, Eisai, Mundipharma, AstraZeneca, Novartis, Lilly, Meiji Seika Kaisha, AbbVie, GlaxoSmithKline, Genmab, Sumitomo Pharma Oncology, CSL Behring

Research Funding: Janssen (Inst), Celgene (Inst), AbbVie (Inst), Takeda (Inst), Bristol Myers Squibb (Inst), Ono Pharmaceutical (Inst), Zenyaku Kogyo (Inst), AstraZeneca (Inst), Chugai Pharma (Inst), Solasia Pharma (Inst), Kyowa Kirin (Inst), Nippon Shinyaku (Inst), Daiichi Sankyo (Inst), Eisai (Inst), Genmab (Inst), Lilly Japan (Inst), Regeneron (Inst), Incyte Japan (Inst), HUYA Bioscience International (Inst)

Francisco Hernandez-Ilizaliturri

Consulting or Advisory Role: Seagen, Pharmacyclics, Novartis, Kite/Gilead, Epizyme, Morphosys, BeiGene, AbbVie

Anita Kumar

Stock and Other Ownership Interests: Bridgebio

Consulting or Advisory Role: Celgene, Kite, a Gilead company, AstraZeneca/MedImmune, Janssen, Genentech, Loxo/Lilly

Research Funding: AbbVie/Genentech, Adaptive Biotechnologies, Celgene, Seagen, AstraZeneca/MedImmune, Pharmacyclics, MorphoSys/Incyte, Loxo/Lilly

Timothy S. Fenske

Stock and Other Ownership Interests: Merck

Honoraria: Adaptive Biotechnologies, AstraZeneca, BeiGene, Kite, a Gilead company, MorphoSys, Pharmacyclics, Sanofi, Seagen, Servier, TG Therapeutics

Consulting or Advisory Role: Adaptive Biotechnologies, BeiGene, MorphoSys, Pharmacyclics, Seagen, Servier, TG Therapeutics

Speakers' Bureau: AstraZeneca, BeiGene, Kite, a Gilead company, Sanofi, Seagen, TG Therapeutics

Expert Testimony: Bayer

Travel, Accommodations, Expenses: AstraZeneca, Kite, a Gilead company, Sanofi, Seagen, TG Therapeutics

John F. Seymour

Honoraria: AbbVie, Janssen, Roche, BMS, AstraZeneca, Gilead Sciences, BeiGene

Consulting or Advisory Role: AbbVie, Janssen, Roche, AstraZeneca, BMS, Gilead Sciences, TG Therapeutics, Genor BioPharma, BeiGene

Speakers' Bureau: AbbVie, Roche

Research Funding: AbbVie, Celgene, Janssen, Roche

Patents, Royalties, Other Intellectual Property: Named patent holder for venetolcax dose ramp up and combination treatment. I do not receive any royalties

Expert Testimony: Roche, TG Therapeutics

Travel, Accommodations, Expenses: AbbVie, Roche

Andrew D. Zelenetz

Honoraria: NCCN, Curio Science, OncLive/MJH Life Sciences

Consulting or Advisory Role: Genentech/Roche, Celgene, AstraZeneca, Dava Oncology, BeiGene, MEI Pharma, Kite, a Gilead company, Juno/Celgene/Bristol Myers Squibb, Sandoz, Ono Pharmaceutical

Research Funding: Genentech/Roche, MEI Pharma, BeiGene, AbbVie (Inst)

Travel, Accommodations, Expenses: Kite, a Gilead company, NCCN, BeiGene

Binoj Nair

Employment: Loxo/Lilly

Stock and Other Ownership Interests: Lilly

Donald E. Tsai

Employment: Loxo at Lilly

Stock and Other Ownership Interests: Lilly, TG Therapeutics

Patents, Royalties, Other Intellectual Property: Patent on retinoic acid compounds

Travel, Accommodations, Expenses: Loxo at Lilly

Minna Balbas

Employment: Loxo

Stock and Other Ownership Interests: Lilly, ORIC Pharmaceuticals

Richard A. Walgren

Employment: Lilly

Stock and Other Ownership Interests: Lilly

Patents, Royalties, Other Intellectual Property: Patent applicant/holder, without royalties, for therapeutic applications related to ramucirumab and merestinib (Inst)

Paolo Abada

Employment: Lilly

Stock and Other Ownership Interests: Lilly

Chunxiao Wang

Employment: Lilly

Stock and Other Ownership Interests: Lilly

Junjie Zhao

Employment: Loxo

Stock and Other Ownership Interests: Loxo/Lilly

Anthony R. Mato

Consulting or Advisory Role: TG Therapeutics, AbbVie/Genentech, Pharmacyclics, Adaptive Biotechnologies, Johnson & Johnson, Acerta Pharma/AstraZeneca, Loxo/Lilly, Curio/Vaniam Group, Merck, Bristol Myers Squibb/Pfizer, PerView, DAVA Oncology, BMS, Genmab, AXIS Education, PER

Research Funding: Regeneron, TG Therapeutics, Sunesis Pharmaceuticals, Loxo, AbbVie/Genentech, Pharmacyclics, Adaptive Biotechnologies, Johnson & Johnson, Acerta Pharma/AstraZeneca, DTRM, Genmab, Nurix

Nirav N. Shah

Stock and Other Ownership Interests: Tundra Targeted Therapeutics

Consulting or Advisory Role: Kite, a Gilead company, Loxo/Lilly, TG Therapeutics, Seagen, Incyte, Novartis, Juno/Bristol-Myers Sqibb, Janssen Oncology

Research Funding: Miltenyi Biotec, Loxo/Lilly, Adaptive Biotechnologies

Travel, Accommodations, Expenses: Miltenyi Biotec

No other potential conflicts of interest were reported.


FIG 1.
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