PO.CTP01.03 · 进行中的临床试验
Larotrectinib (L) in patients (pts) with solid tumors with NTRK1/2/3 amplification (amp): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study
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作者与单位
摘要 Abstract
Background: TAPUR is a phase II basket study evaluating antitumor activity of commercially available targeted agents in pts with advanced cancers with specific genomic alterations. Results in a cohort of pts with solid tumors with NTRK1/2/3 amp treated with L are reported.
Methods: Eligible pts had measurable disease, ECOG performance status (PS) 0-2, adequate organ function, and no remaining standard treatment (tx) options. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Amp cut-offs were defined per NGS providers. Tumors must not have had NTRK fusions. L dosing was one 100 mg capsule or oral solution twice daily until disease progression or unacceptable toxicity. Primary endpoint was disease control (DC) per investigator defined as objective response (OR) or stable disease (SD) of at least 16+ weeks (wks) duration (SD16+) per RECIST v1.1. Simon 2-stage design tested the null DC rate of 20% vs. 45% (power = 0.85, alpha=0.10). If ≥2 of 8 pts in stage 1 had DC, 13 more pts were enrolled; otherwise, the cohort was closed for futility. Secondary endpoints were OR, progression-free survival (PFS), overall survival (OS), duration of response and SD, and safety.
Results: 8 pts with solid tumors (breast [n=3], soft tissue sarcoma [n=2], head and neck [n=1], non-small cell lung cancer (LC) [n=1], small cell LC [n=1]) with NTRK1 amp (n=5), NTRK2 amp (n=1), NTRK1 amp and mutation (mut) (n=1), and NTRK1 amp and NTRK3 mut (n=1) were enrolled. All pts were evaluable for efficacy. Table shows demographics and outcomes. SD16+ was observed in 1 pt with myxoliposarcoma and NTRK 1 amp for a DC rate of 13% (1-sided 90% CI, 1 to 100) and an OR rate of 0% (95% CI, 0 to 37). Duration of SD in 1 pt was 24 wks. The null DC rate was not rejected (p=0.83). No pts had grade 3-5 tx-related adverse or serious adverse events.
Conclusions: L did not meet prespecified criteria to declare a signal of activity in pts with solid tumors with NTRK amp.
Table: Demographics and Efficacy Outcomes (N=8) Median (Med) age, years (range) 52 (37, 67) Female, No. (%) 5 (63) ECOG PS, No. (%) 0 3 (38) 1 5 (63) Prior systemic regimens, No. (%) 1 1 (13) 2 2 (25) ≥3 5 (63) DC rate, % (OR or SD16+) (1-sided 90% CI), p-value 13 (1, 100), (p=0.83) OR rate, % (95% CI) 0 (0, 37) Med PFS, wks (95% CI) 7 (2, 9) Med OS, wks (95% CI) 18 (2, Not reported) Duration of SD in pt with SD16+, wks 24 1 Percentages may not sum to 100% due to rounding
利益披露 Disclosure
J. Rodon,
280 Bio, Adcentrix, Alnylam, Alterome, Beigene, Bicycle Therapeutics, Biohaven, Blueprint Medicines, Cancer Core Europe, Cogent, Eli Lilly, Ensem, ForeBio, Hummingbird, Ideaya, Immuneering Corp ).
Incyte, Insilico Medicines, Ipsen, Kelun-Biotech, Merck Sharp & Dohme, Novartis, Nuvectis Pharma, Parabilis Pharmaceuticals, Pfizer, Relay, Roche Pharmaceuticals, Scorpion Therapeutics, Seed ).
Tango Therapeutics, Tyra, Vividion, Zai Labs ).
American Society of Medical Oncology (ASMO), Dava Oncology, European Society for Medical Oncology (ESMO), STOP Cancer Travel.
Amgen ), Travel, Other, Consulting.
AstraZeneca ), Other, Consulting.
BioHybrid Solutions Travel, Other, Consulting, Scientific Advisory Board.
Boxer Capital LLC Other, Consulting.
Bridgebio ), Travel, Other, Consulting.
Bristol Myers Squibb (BMS) ), Travel, Other, Consulting.
Debio ), Travel, Other, Consulting.
Ecor1 Other, Consulting.
Guidepoint Other, Consulting.
Ionctura Travel, Other, Consulting.
Merus Travel, Other, Consulting.
MonteRosa ), Travel, Other, Consulting.
Tang Advisors, LLC Other, Consulting.
Vall d'Hebron Institute of Oncology (VHIO) ), Other, Consulting.
M. Rothe, None..
E. Garrett-Mayer, None.
N. Rohatgi,
Astra Zeneca Independent Contractor.
Daiichi Sankyo Independent Contractor.
Lilly Independent Contractor.
Gilead Independent Contractor.
BMS Independent Contractor.
Stemline/Menarini Independent Contractor.
Merck Independent Contractor.
Natera Independent Contractor.
Novartis Independent Contractor.
Pfizer Independent Contractor.
Astellas Independent Contractor.
Agendia Independent Contractor.
A. G. Menendez, None.
L. A. Elliott,
Deciphera Other, Advisory Board.
EMD Serono Other, Advisory Board.
A. Gregory, None.
A. Gregory,
Pfizer Other, Employment of immediate family member
Stock options held by immediate family member.
D. C. Hinshaw, None..
G. N. Grantham, None.
S. Halabi,
BMS Other, Member of DSMB.
CG Oncology Other, Member of DSMB.
Janssen Other, Member of DSMB.
Sanofi Other, Member of DSMB.
R. L. Schilsky,
Clarified Precision Medicine Stock Option, Other, Leadership Position.
Leap Therapeutics Stock, Other, Leadership Position.
Cellworks Independent Contractor, Stock Option, Other, Consulting/Advisory Role.
ZephyrAI Independent Contractor, Other, Consulting/Advisory Role.
Flatiron Health Independent Contractor, Other, Consulting or Advisory Role.
Toray Industries Other, Honoraria for service on a study for DSMB.
AstraZeneca Other, Research Funding to ASCO in support of the TAPUR Study.
Bayer Other, Research Funding to ASCO in support of the TAPUR Study.
Bristol Myers Squibb Other, Research Funding to ASCO in support of the TAPUR Study.
Genentech/Roche Other, Research Funding to ASCO in support of the TAPUR Study.
Lilly Other, Research Funding to ASCO in support of the TAPUR Study.
Merck Other, Research Funding to ASCO in support of the TAPUR Study.
Pfizer Other, Research Funding to ASCO in support of the TAPUR Study.
Boehringer Ingelheim Other, Research Funding to ASCO in support of the TAPUR Study.
Taiho Oncology Other, Research Funding to ASCO in support of the TAPUR Study.
WUGEN, Inc. Other, Honoraria for service as a DSMB Member.
AbbVie Other, Honorarium for lecture.
Sygnomics Independent Contractor, Other, consulting or advisory role.