A. Hannah (South San Francisco, CA, United States of America)

CytomX Therapeutics

Author Of 1 Presentation

 On-Demand ePoster Display

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.

Collapse