E. Hamilton (Nashville, TN, United States of America)
Sarah Cannon Research Institute/Tennessee OncologyAuthor Of 1 Presentation
Challenges and pitfalls of early drug development in early breast cancer (ID 37)
Presenter Of 1 Presentation
Challenges and pitfalls of early drug development in early breast cancer (ID 37)
Moderator Of 1 Session
Author Of 2 Presentations
- K. Miller (Indianapolis, IN, United States of America)
- L. Emens (Pittsburgh, United States of America)
- S. Tolaney (Boston, MA, United States of America)
- S. Hurvitz (Santa Monica, CA, United States of America)
- E. Hamilton (Nashville, TN, United States of America)
- V. Paton (South San Francisco, CA, United States of America)
- A. Hannah (South San Francisco, CA, United States of America)
- V. Boni (Madrid, Spain)
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.
128TiP - HER2CLIMB-04: Phase 2 trial of tucatinib + trastuzumab deruxtecan in patients with HER2+ unresectable locally-advanced or metastatic breast cancer with and without brain metastases (Trial in Progress)
Abstract
Background
Tucatinib (TUC) is an oral, reversible, small molecule tyrosine kinase inhibitor highly selective for human epidermal growth factor receptor 2 (HER2). In the HER2CLIMB trial (NCT02614794), the combination of TUC + trastuzumab (T) + capecitabine (C) demonstrated statistically significant and clinically meaningful improvement in progression free survival (PFS), overall survival (OS), and PFS in patients (pts) with brain metastases (BM) compared to T + C alone, supporting regulatory approvals internationally for pts with HER2+ metastatic breast cancer (MBC). Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate with a topoisomerase I inhibitor payload approved in the US for treatment of HER2+ MBC in pts who have received 2 or more prior anti-HER2 regimens in the metastatic setting. Approval was based on data from the Destiny-Breast01 trial (NCT03248492) where treatment with T-DXd resulted in a confirmed objective response rate (cORR) of 61.4% (95% CI: 54.0, 68.5) in pts with HER2+ MBC who had prior ado-trastuzumab emtansine treatment. Despite these advances, HER2+ MBC remains incurable, and pts will eventually progress on currently available therapies. Combining TUC and T-DXd may result in further improvement on the efficacy seen with either agent.
Trial design
HER2CLIMB-04 (NCT04539938) is a single arm, open-label phase II trial evaluating safety and antitumor activity of TUC + T-DXd in pts with HER2+ unresectable locally-advanced or MBC who have received 2 or more prior HER2-based regimens in the metastatic setting. Pts with BM, including active BM, may be enrolled. Ten pts will be enrolled in the safety lead-in portion of the study and followed for at least 1 cycle. If safety of the combination is acceptable, the trial will continue until approximately 60 response-evaluable pts have been enrolled, approximately evenly distributed between pts with and without BM. The primary endpoint is cORR by investigator (INV) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Secondary endpoints are PFS, duration of response, and disease control rate by INV per RECIST v1.1, OS, and safety. Enrollment began in late 2020.
Clinical trial identification
NCT04539938.
Editorial acknowledgement
Editorial/writing assistance was provided by Wendi Schultz and Aulma Parker of Seagen Inc.
Legal entity responsible for the study
Seagen Inc.
Funding
Seagen Inc.
Disclosure
E. Hamilton: Advisory/Consultancy, Paid to Institution Only: Pfizer, Genentech/Roche, Lilly, Puma Biotechnology, Daiichi Sankyo, Mersana Therapeutics, Boehringer Ingelheim, AstraZeneca, Novartis, Silverback Therapeutics, Black Diamond, and NanoString; Research grant/Funding (institution), Paid to Institution Only: Seagen Inc., Puma, AstraZeneca, Hutchinson MediPharma, OncoMed, MedImmune, StemCentrx, Genentech/Roche, Curis, Verastem, Zymeworks, Syndax, Lycera, Rgenix, Novartis, Mersana, Millenium, TapImmune, Lilly, BerGenBio, Medivation, Pfizer, Tesaro, Boehringer Ingelheim. J. Ramos: Shareholder/Stockholder/Stock options: Seagen Inc.; Full/Part-time employment: Seagen Inc. W. Feng: Shareholder/Stockholder/Stock options: Seagen Inc.; Full/Part-time employment: Seagen Inc. I. Krop: Honoraria (self): Celltrion; Advisory/Consultancy: Daiichi Sankyo, Genentech/Roche, Ionis Pharma, Macrogenics, Merck, Novartis, Seagen Inc., Celltrion, BMS; Advisory/Consultancy, DSMB membership: Merck, Novartis; Research grant/Funding (institution): Daiichi Sankyo, Genentech, Pfizer, Seagen, Taiho Oncology; Spouse/Financial dependant, Stock/Stockholder, Leadership, and/or Employment: AMAG Pharma, Freeline.
Presenter Of 1 Presentation
128TiP - HER2CLIMB-04: Phase 2 trial of tucatinib + trastuzumab deruxtecan in patients with HER2+ unresectable locally-advanced or metastatic breast cancer with and without brain metastases (Trial in Progress)
Abstract
Background
Tucatinib (TUC) is an oral, reversible, small molecule tyrosine kinase inhibitor highly selective for human epidermal growth factor receptor 2 (HER2). In the HER2CLIMB trial (NCT02614794), the combination of TUC + trastuzumab (T) + capecitabine (C) demonstrated statistically significant and clinically meaningful improvement in progression free survival (PFS), overall survival (OS), and PFS in patients (pts) with brain metastases (BM) compared to T + C alone, supporting regulatory approvals internationally for pts with HER2+ metastatic breast cancer (MBC). Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate with a topoisomerase I inhibitor payload approved in the US for treatment of HER2+ MBC in pts who have received 2 or more prior anti-HER2 regimens in the metastatic setting. Approval was based on data from the Destiny-Breast01 trial (NCT03248492) where treatment with T-DXd resulted in a confirmed objective response rate (cORR) of 61.4% (95% CI: 54.0, 68.5) in pts with HER2+ MBC who had prior ado-trastuzumab emtansine treatment. Despite these advances, HER2+ MBC remains incurable, and pts will eventually progress on currently available therapies. Combining TUC and T-DXd may result in further improvement on the efficacy seen with either agent.
Trial design
HER2CLIMB-04 (NCT04539938) is a single arm, open-label phase II trial evaluating safety and antitumor activity of TUC + T-DXd in pts with HER2+ unresectable locally-advanced or MBC who have received 2 or more prior HER2-based regimens in the metastatic setting. Pts with BM, including active BM, may be enrolled. Ten pts will be enrolled in the safety lead-in portion of the study and followed for at least 1 cycle. If safety of the combination is acceptable, the trial will continue until approximately 60 response-evaluable pts have been enrolled, approximately evenly distributed between pts with and without BM. The primary endpoint is cORR by investigator (INV) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Secondary endpoints are PFS, duration of response, and disease control rate by INV per RECIST v1.1, OS, and safety. Enrollment began in late 2020.
Clinical trial identification
NCT04539938.
Editorial acknowledgement
Editorial/writing assistance was provided by Wendi Schultz and Aulma Parker of Seagen Inc.
Legal entity responsible for the study
Seagen Inc.
Funding
Seagen Inc.
Disclosure
E. Hamilton: Advisory/Consultancy, Paid to Institution Only: Pfizer, Genentech/Roche, Lilly, Puma Biotechnology, Daiichi Sankyo, Mersana Therapeutics, Boehringer Ingelheim, AstraZeneca, Novartis, Silverback Therapeutics, Black Diamond, and NanoString; Research grant/Funding (institution), Paid to Institution Only: Seagen Inc., Puma, AstraZeneca, Hutchinson MediPharma, OncoMed, MedImmune, StemCentrx, Genentech/Roche, Curis, Verastem, Zymeworks, Syndax, Lycera, Rgenix, Novartis, Mersana, Millenium, TapImmune, Lilly, BerGenBio, Medivation, Pfizer, Tesaro, Boehringer Ingelheim. J. Ramos: Shareholder/Stockholder/Stock options: Seagen Inc.; Full/Part-time employment: Seagen Inc. W. Feng: Shareholder/Stockholder/Stock options: Seagen Inc.; Full/Part-time employment: Seagen Inc. I. Krop: Honoraria (self): Celltrion; Advisory/Consultancy: Daiichi Sankyo, Genentech/Roche, Ionis Pharma, Macrogenics, Merck, Novartis, Seagen Inc., Celltrion, BMS; Advisory/Consultancy, DSMB membership: Merck, Novartis; Research grant/Funding (institution): Daiichi Sankyo, Genentech, Pfizer, Seagen, Taiho Oncology; Spouse/Financial dependant, Stock/Stockholder, Leadership, and/or Employment: AMAG Pharma, Freeline.