S. Hurvitz (Santa Monica, CA, United States of America)

UCLA Hematology/Oncology Santa Monica

Author Of 2 Presentations

 Conference Calendar
Adjuvant treatment early HER+ in breast cancer Educational session

Current standard approaches for early stage HER2+ disease (ID 28)

Lecture Time
16:35 - 16:50
Speakers
Session Name
Adjuvant treatment early HER+ in breast cancer
Room
Channel 1
Date
Sat, 08.05.2021
Time
16:30 - 17:45
Mini Oral session 1 Mini oral

93MO - Overall survival (OS) results by age subgroup from the phase III MONALEESA-7 (ML-7) trial of premenopausal patients (pts) with HR+/HER2? advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib (RIB) (ID 257)

Presentation Number
93MO
Lecture Time
12:50 - 12:55
Speakers
Session Name
Mini Oral session 1
Room
Channel 2
Date
Fri, 07.05.2021
Time
12:45 - 13:45

Abstract

Background

RIB, a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i), significantly prolonged OS in pre- or perimenopausal pts with HR+/HER2− ABC in ML-7 with updated results (median, 58.7 vs 48.0 mo for RIB + ET vs placebo [PBO] + ET; HR, 0.76 [95% CI, 0.61-0.96]; NCT02278120). Younger pts with HR+/HER2− ABC tend to have a poorer prognosis. We conducted an exploratory analysis to characterize outcomes in pts <40 vs ≥40 y of age.

Methods

Pre- or perimenopausal pts with HR+/HER2− ABC with no prior CDK4/6i or ET for ABC were randomized 1:1 to receive RIB or PBO plus goserelin and a nonsteroidal aromatase inhibitor (NSAI) or tamoxifen. OS and other efficacy endpoints were evaluated by Cox proportional hazards model and summarized using Kaplan-Meier methods.

Results

The median follow-up time was 53.5 mo (data cutoff, 29 June 2020). In the RIB vs PBO arm, 98 vs 88 pts were <40 y and 237 vs 249 pts were ≥40 y. Median age (range) in RIB vs PBO was 35 y (25-39 y) vs 36 y (29-39 y) in pts <40 y, and 45 y (40-58 y) vs 46 y (40-58 y) in pts ≥40 y. In pts <40 y, RIB + ET demonstrated an OS benefit vs PBO + ET (median, 51.3 vs 40.5 mo; HR, 0.65; 95% CI, 0.43-0.98). RIB had a longer median OS vs PBO in pts ≥40 y (median, 58.8 vs 51.7 mo; HR, 0.81; 95% CI, 0.62-1.07). Similar trends were observed for OS in NSAI-treated pts and in all pts for PFS2, time to chemotherapy (CT), and CT-free survival (Table). In pts who discontinued, subsequent antineoplastic therapies were received by 77.3% vs 75.0% of pts age <40 y in RIB vs PBO arms, respectively, and 77.2% vs 79.2% of pts ≥40 y. Subsequent CDK4/6i were received in 16.0% vs 27.5% of pts age <40 y and 11.6% vs 25.7% of pts ≥40 y in RIB vs PBO arms. Adverse events were consistent with the known safety profile of ML-7.

Age <40 y Age ≥40 y
RIB + ET PBO + ET RIB + ET PBO + ET
OS in NSAI cohort n=78 n=66 n=170 n=181
Events, n (%) 36 (46.2) 39 (59.1) 71 (41.8) 81 (44.8)
Median, mo 50.2 40.7 58.7 54.1
HR (95% CI) 0.66 (0.42-1.05) 0.85 (0.61-1.16)
PFS2a n=98 n=88 n=237 n=249
Events, n (%) 54 (55.1) 60 (68.2) 123 (51.9) 161 (64.7)
Median, mo 46.0 25.5 43.6 32.7
HR (95% CI) 0.59 (0.40-0.86) 0.71 (0.56-0.89)
Time to first CTa n=98 n=88 n=237 n=249
Events, n (%) 40 (40.8) 43 (48.9) 104 (43.9) 130 (52.2)
Median, mo NR 36.6 50.2 36.8
HR (95% CI) 0.65 (0.42-1.01) 0.69 (0.53-0.90)
CT-free survivala n=98 n=88 n=237 n=249
Events, n (%) 53 (54.1) 63 (71.6) 137 (57.8) 173 (69.5)
Median, mo 46.5 22.7 41.5 27.6
HR (95% CI) 0.58 (0.40-0.85) 0.68 (0.54-0.85)

ITT, intent to treat; NR, not reached. aIn ITT.

Conclusions

In ML-7, RIB prolonged OS and improved post-progression outcomes in HR+/HER2− ABC, particularly in younger pts, who have a substantial unmet need.

Clinical trial identification

NCT02278120.

Editorial acknowledgement

This abstract was developed with editorial assistance provided by Chris Carter, PhD of MediTech Media, LLC. Editorial support was funded by Novartis Pharmaceuticals Corporation.

Legal entity responsible for the study

Novartis Pharmaceuticals Corporation.

Funding

Novartis Pharmaceuticals Corporation.

Disclosure

Y-S. Lu: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Honoraria (self), Speaker Bureau/Expert testimony: Roche; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Merck Sharp & Dohme; Honoraria (self), Speaker Bureau/Expert testimony: Eisai. N.S. El Saghir: Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Eli Lilly; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: AstraZeneca. S.A. Hurvitz: Research grant/Funding (institution): Ambryx; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Bayer; Research grant/Funding (institution), Travel/Accommodation/Expenses: OBI Pharma; Research grant/Funding (institution): Bimarin; Research grant/Funding (institution): Cascadian; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Dignitana; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): GSK; Research grant/Funding (institution), Travel/Accommodation/Expenses: Lilly; Research grant/Funding (institution): Macrogenics; Research grant/Funding (institution): Medivation; Research grant/Funding (institution): Merrimack; Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Pieris; Research grant/Funding (institution): Puma; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Seattle Genetics. D. Tripathy: Honoraria (self), Advisory/Consultancy: Genomic Health; Honoraria (self), Advisory/Consultancy: GlaxoSmithKline; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Polyphor; Advisory/Consultancy: Puma Biotechnology; Honoraria (self), Speaker Bureau/Expert testimony: AstraZeneca; Leadership role: OncoPep; Advisory/Consultancy: Sellas Life Sciences Group. F. Cardoso: Honoraria (self): Novartis; Honoraria (self): Amgen; Honoraria (self): Astellas/Medivation; Honoraria (self): AstraZeneca; Honoraria (self): Celgene; Honoraria (self): Daiichi Sankyo; Honoraria (self): Eisai; Honoraria (self): GE Oncology; Honoraria (self): Genentech; Honoraria (self): GSK; Honoraria (self): Macrogenics; Honoraria (self): Medscape; Honoraria (self): Merck-Sharp; Honoraria (self): Merus; Honoraria (self): Mylan; Honoraria (self): Mundipharma; Honoraria (self): Pfizer; Honoraria (self): Pierre Fabre; Honoraria (self): Prime; Honoraria (institution): Roche. M.A. Colleoni: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Pierre Fabre; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self): Novartis; Honoraria (self), Advisory/Consultancy: OBI Pharma; Honoraria (self), Advisory/Consultancy: Puma Biotechnology; Honoraria (self), Advisory/Consultancy: Celldex. S. Campos-Gomez: Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb. C. Wang, Y. Wang, J.P. Zarate, A. Chakravartty: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis. S-A. Im: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy: Hanmi; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Eisai; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Amgen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): MediPacto; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Lilly; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): GSK; Research grant/Funding (institution): Daewoong. All other authors have declared no conflicts of interest.

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Presenter Of 1 Presentation

 Conference Calendar
Adjuvant treatment early HER+ in breast cancer Educational session

Current standard approaches for early stage HER2+ disease (ID 28)

Lecture Time
16:35 - 16:50
Speakers
Session Name
Adjuvant treatment early HER+ in breast cancer
Room
Channel 1
Date
Sat, 08.05.2021
Time
16:30 - 17:45

Author Of 2 Presentations

 On-Demand ePoster Display

126TiP - HER2CLIMB-02: Tucatinib or placebo with T-DM1 for unresectable locally-advanced or metastatic HER2+ breast cancer

Abstract

Background

Tucatinib (TUC), an oral tyrosine kinase inhibitor (TKI) highly selective for HER2 with minimal inhibition of EGFR, is approved in the US, Canada, Switzerland, Australia, and Singapore for combined treatment with trastuzumab (Tras) and capecitabine for patients with HER2+ metastatic breast cancer (MBC), including patients with brain metastases (BM) who received 1 or more prior anti-HER2-based regimens in the metastatic setting. Ado-Tras emtansine (T-DM1), approved for treatment of HER2+ MBC after Tras and a taxane, has improved progression-free survival (PFS) and overall survival (OS). Further improvements are needed, including in patients with active BM. A phase Ib trial evaluated TUC+T-DM1 in 50 patients with HER2+ MBC who received prior treatment with Tras and a taxane; 60% of patients had BM at baseline (Borges 2018). Common adverse events, mostly Grade 1/2, were nausea (72%), diarrhea (60%), and fatigue (56%). Median PFS was 8.2 months and objective response rate (ORR) in patients with measurable disease (n=34) was 47%. Brain specific response rate (RECIST v1.1) in patients with measurable BM (n=14) was 36%. This encouraging clinical activity, including in patients with BM, provides rationale to evaluate TUC+T-DM1.

Trial design

HER2CLIMB-02 is a randomized, double-blind, placebo-controlled, phase III study enrolling patients with centrally confirmed HER2+ unresectable locally-advanced or MBC previously treated with Tras and taxane. Patients must have ECOG ≤1. Approximately 460 patients will be randomized 1:1 for 21-day cycles of TUC (300 mg PO BID) or placebo with T-DM1 (3.6 mg/kg IV). Prior treatment with investigational anti-HER2 agent, anti-EGFR agent, or HER2 TKI is not permitted. Prior pertuzumab treatment is permitted. Baseline brain MRIs are required; patients with stable, progressing, or untreated BM may be eligible. Treatment response assessments per RECISTv1.1 occur every 6 weeks for the first 24 weeks, and then every 9 weeks. Primary endpoint is PFS per investigator assessment, with OS and ORR as key secondary endpoints. Enrollment is ongoing in the US, Canada, EU, Japan, South Korea, Australia, and Israel, and is planned for Singapore.

Clinical trial identification

NCT03975647.

Editorial acknowledgement

Editorial assistance was provided by Craig Bolte of MMS Holdings.

Legal entity responsible for the study

Seagen Inc.

Funding

Seagen Inc.

Disclosure

S.A. Hurvitz: Research grant/Funding (institution): Ambrx, Amgen; Research grant/Funding (institution): AstraZeneca, Arvinas; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Genentech/Roche, Bayer; Research grant/Funding (institution): Gilead, Immunomedics; Research grant/Funding (institution): GlaxoSmithKline; Research grant/Funding (institution), Travel/Accommodation/Expenses: Eli Lilly; Research grant/Funding (institution): Macrogenetics, Novartis; Research grant/Funding (institution): Pfizer, Obi Pharma; Research grant/Funding (institution): Pieris, Puma; Research grant/Funding (institution): Radius, Sanofi; Research grant/Funding (institution): Seagen Inc.; Research grant/Funding (institution): Dignitana, Zymeworks; Research grant/Funding (institution): Phoenix Molecular Designs, Ltd.; Shareholder/Stockholder/Stock options: Nk Max. N. Harbeck: Honoraria (self): AstraZeneca; Honoraria (self): Daiichi Sankyo; Honoraria (self): Eli Lilly; Honoraria (self): MSD Pharmaceuticals; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Roche; Honoraria (self): Sandoz/Hexal; Honoraria (self): Seagen Inc. L. Vahdat: Advisory/Consultancy, Research grant/Funding (institution): Arvinas; Advisory/Consultancy: Roche; Advisory/Consultancy: Berg Pharma; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eisai Co., Ltd.; Advisory/Consultancy, Research grant/Funding (institution): Polyphor Pharma; Advisory/Consultancy, Travel/Accommodation/Expenses: Seagen Inc.; Research grant/Funding (institution): Genentech/Roche; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution): Oncotherapy Biosciences. S.M. Tolaney: Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy: Daiichi Sankyo, OncoPep; Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly, Eisai; Advisory/Consultancy: G1 Therapeutics, Outcomes4Me; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy, Research grant/Funding (institution): Immunomedics; Advisory/Consultancy: Kyowa Kirin, Silverback Therapeutics; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): NanoString; Advisory/Consultancy, Research grant/Funding (institution): Nektar, Seagen; Advisory/Consultancy, Research grant/Funding (institution): Novartis, Pfizer; Research grant/Funding (institution): Exelixis; Research grant/Funding (institution): Cyclacel, Odonate; Advisory/Consultancy: Puma Therapeutics, Sanofi; Advisory/Consultancy: Celldex, Paxman, AbbVie; Advisory/Consultancy: Samsung Bioepsis Inc. S. Loi: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Aduro Biotech; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy: G1 Therapeutics; Advisory/Consultancy: GlaxoSmithKline; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy, Research grant/Funding (institution): Seagen Inc; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Puma Biotech. N. Masuda: Honoraria (self), Research grant/Funding (institution): Chugai Pharma; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self), Research grant/Funding (institution): Eli Lilly; Honoraria (self), Research grant/Funding (institution): Eisai; Honoraria (self): Takeda; Research grant/Funding (institution): Kyowa-Kirin; Research grant/Funding (institution): MSD Pharma; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Nippon-Kayaku; Research grant/Funding (institution): Daiichi Sankyo. J. O'Shaughnessy: Advisory/Consultancy: AbbVie, Agendia; Advisory/Consultancy: Amgen Biotech; Advisory/Consultancy: Aptitude Health; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Celgene, Eisai; Advisory/Consultancy: G1 Therapeutics; Advisory/Consultancy: Genentech; Advisory/Consultancy: Immunomedics; Advisory/Consultancy: Ipsen Biopharma; Advisory/Consultancy: Jounce Therapeutics; Advisory/Consultancy: Eli Lilly, Merck; Advisory/Consultancy: Myriad, Novartis; Advisory/Consultancy: Ondonate Therapeutics; Advisory/Consultancy: Pfizer, Puma Biotech; Advisory/Consultancy: prIME Oncology; Advisory/Consultancy: Roche, Seagen Inc; Advisory/Consultancy: Syndax Pharmaceuticals. D. Xie: Full/Part-time employment: Seagen Inc. L.N. Walker: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Seagen Inc. E. Rustia: Shareholder/Stockholder/Stock options, Full/Part-time employment: Seagen Inc. V. Borges: Advisory/Consultancy, Research grant/Funding (institution): Seagen Inc; Research grant/Funding (institution): Abbot/AbbVie; Research grant/Funding (institution): Millenium. All other authors have declared no conflicts of interest.

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127TiP - Phase 2, open-label study to evaluate the safety and efficacy of praluzatamab ravtansine (CX 2009) in metastatic HR-positive/HER2 non-amplified breast cancer (mHR+/HER2? BC) and CX-2009 as monotherapy and in combination with pacmilimab in metastatic triple-negative breast cancer (mTNBC)

Abstract

Background

Probody® therapeutics (Pb-Tx) are masked antibodies designed to be conditionally activated in the tumor microenvironment by tumor-associated proteases. This allows Pb-Tx to address previously undruggable targets (eg, CD166) that are highly expressed in both tumor and normal tissue. CX-2009 is a Probody drug conjugate of a masked anti-CD166 monoclonal antibody conjugated to DM4. A phase I CX-2009 monotherapy study showed safety and durable clinical activity (clinical benefit rate at 24 weeks [CBR24] 35%) in patients (pts) with mHR+/HER2− BC or mTNBC. Pacmilimab, a Probody PD-L1 inhibitor, showed acceptable safety in a recent phase I study.

Trial design

This phase II, open-label study with 3 parallel arms (n≈40/arm) will evaluate CX-2009 monotherapy (7 mg/kg Q3W) in pts with mHR+/HER2− BC or mTNBC, and CX-2009 (7 mg/kg Q3W) combined with pacmilimab (1200 mg Q3W) in pts with mTNBC. Adult pts with an ECOG PS of 0–1, measurable disease, and willingness to receive ocular prophylaxis for DM4-related toxicities will be enrolled. Key eligibility criteria for the mHR+/HER2− BC cohort include 2–4 metastatic prior regimens (excluding single-agent hormonal therapy). HR+/HER2− BC cohorts will enroll without screening for CD166. Pts with mTNBC must be CD166+ by IHC and have received 1–3 prior metastatic regimens. For mTNBC pts who receive the doublet, key exclusion criteria include known PD-L1–negative tumor status, history of or active autoimmune disease, and progression within 120 days of 1st dose of an immuno-oncology agent. Pts with corneal disorders will be excluded. The primary endpoint is overall response rate (ORR) assessed by an independent radiology committee per RECIST v1.1. Secondary endpoints include ORR by investigator, duration of response, CBR16 & 24, progression-free survival, and overall survival. This study will also evaluate safety and tolerability, pharmacokinetics, and antidrug antibodies with CX-2009 as monotherapy and in combination with pacmilimab. This trial is enrolling (NCT04596150).

Clinical trial identification

NCT04596150.

Editorial acknowledgement

Mark Phillips, PharmD, MBA, CMPP of Phillips Gilmore Oncology Communications, Inc., Philadelphia, PA, USA provided medical editing assistance, which was funded by CytomX.

Legal entity responsible for the study

CytomX Therapeutics, Inc., South San Francisco, CA, USA.

Funding

CytomX Therapeutics, Inc., South San Francisco, CA, USA.

Disclosure

K.D. Miller: Research grant/Funding (institution): CytomX. L.A. Emens: Licensing/Royalties: Aduro; Licensing/Royalties: IND; Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Celgene; Honoraria (self), Advisory/Consultancy: Chugai; Advisory/Consultancy, no compensation: CytomX; Advisory/Consultancy, no compensation: eTHeRNA; Advisory/Consultancy, Travel/Accommodation/Expenses: Genentech; Honoraria (self), Advisory/Consultancy: Gritstone; Honoraria (self), Advisory/Consultancy: MedImmune; Honoraria (self), Advisory/Consultancy: Molecuvax; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Macrogenics; Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy: Peregrine; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Replimune; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche. S.M. Tolaney: Research grant/Funding (institution): CytomX; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Eli Lilly; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Nektar; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution): Exelixis; Honoraria (self), Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Eisai; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): NanoString; Honoraria (self): Puma; Research grant/Funding (institution): Cyclacel; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Sanofi; Honoraria (self), Advisory/Consultancy: Celldex; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Odonate; Honoraria (self), Advisory/Consultancy: Seattle Genetics; Honoraria (self), Advisory/Consultancy: Silverback Therapeutics. S.A. Hurvitz: Research grant/Funding (institution): Ambrx; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Arvinas; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Genentech/Roche; Research grant/Funding (institution): GSK; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Macrogenics; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): OBI Pharma; Research grant/Funding (institution): Pieris; Research grant/Funding (institution): PUMA; Research grant/Funding (institution): Radius; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): Dignitana; Advisory/Consultancy, Shareholder/Stockholder/Stock options: NKMax. E. Hamilton: Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): Puma; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): CytomX; Research grant/Funding (institution): Hutchinson; Research grant/Funding (institution): MediPharma; Research grant/Funding (institution): OncoMed; Research grant/Funding (institution): MedImmune; Research grant/Funding (institution): StemCentrx; Research grant/Funding (institution): Genentech/Roche; Research grant/Funding (institution): Curis; Research grant/Funding (institution): Verastem; Research grant/Funding (institution): Zymeworks; Research grant/Funding (institution): Syndax; Research grant/Funding (institution): Lycera; Research grant/Funding (institution): Rgenix; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Mersana; Research grant/Funding (institution): Millenium; Research grant/Funding (institution): TapImmune. V. Paton, A.L. Hannah: Full/Part-time employment: CytomX. V. Boni: Research grant/Funding (institution): Loxo; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Roche/Genentech; Research grant/Funding (institution): Zenith Therapeutics; Research grant/Funding (institution): Tesaro; Research grant/Funding (institution): CytomX; Research grant/Funding (institution): Puma; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Menarini; Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): Daiichi Sankyo; Honoraria (self), Advisory/Consultancy: Guidepoint; Honoraria (self), Advisory/Consultancy: Oncoart.

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Presenter Of 1 Presentation

 On-Demand ePoster Display

126TiP - HER2CLIMB-02: Tucatinib or placebo with T-DM1 for unresectable locally-advanced or metastatic HER2+ breast cancer

Abstract

Background

Tucatinib (TUC), an oral tyrosine kinase inhibitor (TKI) highly selective for HER2 with minimal inhibition of EGFR, is approved in the US, Canada, Switzerland, Australia, and Singapore for combined treatment with trastuzumab (Tras) and capecitabine for patients with HER2+ metastatic breast cancer (MBC), including patients with brain metastases (BM) who received 1 or more prior anti-HER2-based regimens in the metastatic setting. Ado-Tras emtansine (T-DM1), approved for treatment of HER2+ MBC after Tras and a taxane, has improved progression-free survival (PFS) and overall survival (OS). Further improvements are needed, including in patients with active BM. A phase Ib trial evaluated TUC+T-DM1 in 50 patients with HER2+ MBC who received prior treatment with Tras and a taxane; 60% of patients had BM at baseline (Borges 2018). Common adverse events, mostly Grade 1/2, were nausea (72%), diarrhea (60%), and fatigue (56%). Median PFS was 8.2 months and objective response rate (ORR) in patients with measurable disease (n=34) was 47%. Brain specific response rate (RECIST v1.1) in patients with measurable BM (n=14) was 36%. This encouraging clinical activity, including in patients with BM, provides rationale to evaluate TUC+T-DM1.

Trial design

HER2CLIMB-02 is a randomized, double-blind, placebo-controlled, phase III study enrolling patients with centrally confirmed HER2+ unresectable locally-advanced or MBC previously treated with Tras and taxane. Patients must have ECOG ≤1. Approximately 460 patients will be randomized 1:1 for 21-day cycles of TUC (300 mg PO BID) or placebo with T-DM1 (3.6 mg/kg IV). Prior treatment with investigational anti-HER2 agent, anti-EGFR agent, or HER2 TKI is not permitted. Prior pertuzumab treatment is permitted. Baseline brain MRIs are required; patients with stable, progressing, or untreated BM may be eligible. Treatment response assessments per RECISTv1.1 occur every 6 weeks for the first 24 weeks, and then every 9 weeks. Primary endpoint is PFS per investigator assessment, with OS and ORR as key secondary endpoints. Enrollment is ongoing in the US, Canada, EU, Japan, South Korea, Australia, and Israel, and is planned for Singapore.

Clinical trial identification

NCT03975647.

Editorial acknowledgement

Editorial assistance was provided by Craig Bolte of MMS Holdings.

Legal entity responsible for the study

Seagen Inc.

Funding

Seagen Inc.

Disclosure

S.A. Hurvitz: Research grant/Funding (institution): Ambrx, Amgen; Research grant/Funding (institution): AstraZeneca, Arvinas; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Genentech/Roche, Bayer; Research grant/Funding (institution): Gilead, Immunomedics; Research grant/Funding (institution): GlaxoSmithKline; Research grant/Funding (institution), Travel/Accommodation/Expenses: Eli Lilly; Research grant/Funding (institution): Macrogenetics, Novartis; Research grant/Funding (institution): Pfizer, Obi Pharma; Research grant/Funding (institution): Pieris, Puma; Research grant/Funding (institution): Radius, Sanofi; Research grant/Funding (institution): Seagen Inc.; Research grant/Funding (institution): Dignitana, Zymeworks; Research grant/Funding (institution): Phoenix Molecular Designs, Ltd.; Shareholder/Stockholder/Stock options: Nk Max. N. Harbeck: Honoraria (self): AstraZeneca; Honoraria (self): Daiichi Sankyo; Honoraria (self): Eli Lilly; Honoraria (self): MSD Pharmaceuticals; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Roche; Honoraria (self): Sandoz/Hexal; Honoraria (self): Seagen Inc. L. Vahdat: Advisory/Consultancy, Research grant/Funding (institution): Arvinas; Advisory/Consultancy: Roche; Advisory/Consultancy: Berg Pharma; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eisai Co., Ltd.; Advisory/Consultancy, Research grant/Funding (institution): Polyphor Pharma; Advisory/Consultancy, Travel/Accommodation/Expenses: Seagen Inc.; Research grant/Funding (institution): Genentech/Roche; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution): Oncotherapy Biosciences. S.M. Tolaney: Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy: Daiichi Sankyo, OncoPep; Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly, Eisai; Advisory/Consultancy: G1 Therapeutics, Outcomes4Me; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy, Research grant/Funding (institution): Immunomedics; Advisory/Consultancy: Kyowa Kirin, Silverback Therapeutics; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): NanoString; Advisory/Consultancy, Research grant/Funding (institution): Nektar, Seagen; Advisory/Consultancy, Research grant/Funding (institution): Novartis, Pfizer; Research grant/Funding (institution): Exelixis; Research grant/Funding (institution): Cyclacel, Odonate; Advisory/Consultancy: Puma Therapeutics, Sanofi; Advisory/Consultancy: Celldex, Paxman, AbbVie; Advisory/Consultancy: Samsung Bioepsis Inc. S. Loi: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Aduro Biotech; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy: G1 Therapeutics; Advisory/Consultancy: GlaxoSmithKline; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy, Research grant/Funding (institution): Seagen Inc; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Puma Biotech. N. Masuda: Honoraria (self), Research grant/Funding (institution): Chugai Pharma; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self), Research grant/Funding (institution): Eli Lilly; Honoraria (self), Research grant/Funding (institution): Eisai; Honoraria (self): Takeda; Research grant/Funding (institution): Kyowa-Kirin; Research grant/Funding (institution): MSD Pharma; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Nippon-Kayaku; Research grant/Funding (institution): Daiichi Sankyo. J. O'Shaughnessy: Advisory/Consultancy: AbbVie, Agendia; Advisory/Consultancy: Amgen Biotech; Advisory/Consultancy: Aptitude Health; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Celgene, Eisai; Advisory/Consultancy: G1 Therapeutics; Advisory/Consultancy: Genentech; Advisory/Consultancy: Immunomedics; Advisory/Consultancy: Ipsen Biopharma; Advisory/Consultancy: Jounce Therapeutics; Advisory/Consultancy: Eli Lilly, Merck; Advisory/Consultancy: Myriad, Novartis; Advisory/Consultancy: Ondonate Therapeutics; Advisory/Consultancy: Pfizer, Puma Biotech; Advisory/Consultancy: prIME Oncology; Advisory/Consultancy: Roche, Seagen Inc; Advisory/Consultancy: Syndax Pharmaceuticals. D. Xie: Full/Part-time employment: Seagen Inc. L.N. Walker: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Seagen Inc. E. Rustia: Shareholder/Stockholder/Stock options, Full/Part-time employment: Seagen Inc. V. Borges: Advisory/Consultancy, Research grant/Funding (institution): Seagen Inc; Research grant/Funding (institution): Abbot/AbbVie; Research grant/Funding (institution): Millenium. All other authors have declared no conflicts of interest.

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