Abstract 5901
Background
Cabozantinib (C) is an inhibitor of multiple receptor tyrosine kinases involved in tumor cell proliferation, neovascularization, and immune cell regulation, including MET, VEGFRs, and TAM family of kinases (TYRO3, MER, and AXL). Preclinical/clinical studies suggest that C promotes an immune-permissive environment that may facilitate synergistic effects with checkpoint inhibitors. This Phase 1b study evaluates C in combination with the programmed death ligand (PD-L1) targeting antibody atezolizumab (A) in pts with solid tumors (NCT03170960).
Methods
Safety and clinical activity of C (2 dose levels: 40 mg, 60 mg QD) + A (1200 mg Q3W) administered in 3-week cycles were evaluated in a 3 + 3 dose escalation design. Safety data of all pts and criteria for dose limiting toxicity (DLT) determined the recommended dose (RD) for a subsequent expansion stage. Tumor response was assessed by CT/MRI and bone scan (RECIST v 1.1).
Results
12 pts with treatment-naïve advanced RCC (mostly clear-cell subtype) were treated in the dose escalation stage (6 at each dose level). At data cutoff, all pts were actively receiving study treatment (range, 3–12 cycles). There were no DLTs or serious adverse events (AEs) in either C+A dose cohort. Most AEs were Grade 1/2 including immune-related AEs. Grade 3 AEs included 3 events of hypertension, 2 events each of diarrhea and hypophosphatemia, and 1 pulmonary embolism. There were no Grade 4/5 AEs. Among 10 pts investigator-assessed confirmed ORR was 50% (1 CR, 4 PRs); 2 additional pts had unconfirmed PRs with only 1 tumor assessment at data cut-off.
Conclusions
C+A is well tolerated and shows encouraging anti-tumor activity in advanced RCC. C 40 mg QD + A 1200 mg Q3W was selected as the RD for expansion in multiple solid tumor cohorts including RCC.
Clinical trial identification
NCT03170960.
Legal entity responsible for the study
Exelixis, Inc.
Funding
Exelixis, Inc.
Editorial Acknowledgement
Disclosure
N. Agarwal: Consulting or advisory role: Pfizer, Novartis, Merck, Genentech, Eisai, Exelixis, Clovis, EMD Serono, BMS, AstraZeneca, Astellas. U. Vaishampayan: Honoraria: Astellas Pharma, Bayer, Bristol-Myers Squibb, Exelixis, Genentech, Janssen, Novartis, Pfizer, Sanofi; Consulting or advisory role: Astellas Pharma, Bayer, Bristol-Myers Squibb, Exelixis, Genentech/Roche, Novartis, Pfizer; Speakers' bureau: Astellas Pharma, Bayer, Bristol-Myers Squibb, Exelixis, Genentech/Roche, Novartis, Pfizer, Sanofi; Research funding: Astellas Pharma, Bristol-Myers Squibb, Exelixis, Novartis, Pfizer. M. Green, F. di Nucci: Employee: Genentech. P-Y. Chang: Employee of Exelixis Inc. C. Scheffold: Employee of and owns stock in Exelixis, Inc. S. Pal: Honoraria: Astellas Pharma, Medivation, Novartis; Consulting or advisory role: Aveo, Bristol-Myers Squibb, Exelixis, Genentech, Myriad Pharmaceuticals, Novartis, Pfizer; Research funding: Medivation.
Resources from the same session
4742 - Ki67 as an important predictor for Oncotype Dx Recurrence score risk groups in Early Breast cancer
Presenter: Fernando Namuche
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
4697 - Genetic signatures always suggest undertreatment? Experience with PAM51
Presenter: Carolina Sales
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
3158 - Significance of receptors expression, mitotic index and Ki67 in breast cancer patients with Nottingham Prognostic Index (NPI) poor prognosis score
Presenter: Mejri Nesrine
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
3838 - Subgroup analyses of efficacy from a phase III study comparing SB3 (trastuzumab biosimilar) with reference trastuzumab in early breast cancer patients
Presenter: Javier Cortes Castan
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
715 - Autoimmunity and benefit from trastuzumab treatment in breast cancer: results from the HERA phase 3 trial
Presenter: Amir Sonnenblick
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
2388 - Impact of hormone receptor status in HER2+ early breast cancer: a paradigm shift in the trastuzumab era
Presenter: Alexandre De Nonneville
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
3742 - Sefety profile of subcutaneous trastuzumab in patients with HER2-positive early breast cancer: The french HERMIONE non-interventional prospective study
Presenter: jean-philippe Jacquin
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
3647 - Real-life data on the cardiac toxicity of adjuvant fixed-dose subcutaneous trastuzumab in HER2-positive breast cancer.
Presenter: Rita De Sanctis
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
3837 - Comprehensive evaluation of the pharmacokinetic profiles of SB3 and reference trastuzumab
Presenter: Xavier Pivot
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract
1692 - The impact of neoadjuvant dual HER2 targeting with Pertuzumab and Trastuzumab on pathological complete response (pCR) rates: Kent Oncology Centre (KOC) experience
Presenter: Samantha Forner
Session: Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Resources:
Abstract