H. Rugo (San Francisco, CA, United States of America)

UCSF Helen Diller Family Comprehensive Cancer Center

Author Of 2 Presentations

 Conference Calendar
Proffered Paper session 1 Proffered paper

Invited Discussant 63O and 91O (ID 241)

Lecture Time
14:36 - 14:46
Speakers
Session Name
Proffered Paper session 1
Room
Channel 2
Date
Fri, 07.05.2021
Time
14:15 - 15:30
Mini Oral session 2 Mini oral

96MO - A Risk Analysis of Alpelisib (ALP)-Induced Hyperglycemia (HG) Using Baseline Factors in Patients (pts) With Advanced Solid Tumors and Breast Cancer (BC): A Pooled Analysis of X2101 and SOLAR-1 (ID 272)

Presentation Number
96MO
Lecture Time
13:31 - 13:36
Speakers
Session Name
Mini Oral session 2
Room
Channel 2
Date
Sat, 08.05.2021
Time
12:45 - 14:00

Abstract

Background

ALP + fulvestrant is approved for PIK3CA-mutated, HR+/HER2– advanced BC in the US and EU. HG is an on-target adverse event (AE) of ALP and the most common all grade (G) and G3/4 AE in the phase III SOLAR-1 trial. Antihyperglycemic agents (AHAs) and ALP dose modifications (mods) and discontinuations (discs) were used to manage this AE (Table). We present a pooled risk factor model using safety sets of the phase I X2101 (NCT01219699) and SOLAR-1 (NCT02437318) trials and its application to SOLAR-1 data.

Methods

Pts (505) were randomly divided into training (405 pts) and testing sets (100 pts). Baseline factors for HG were identified, multiple models tested, and a random forest model was used to categorize pts as high or low risk for G3/4 HG based on 5 baseline factors (fasting plasma glucose [FPG], BMI, HbA1c, monocyte counts, and age). Performance metrics will be presented.

Results

The training set identified G3/4 HG in 126/131 high (96.2%) vs 3/274 low risk (1.09%) pts, and was validated in the testing set with 20/33 high (60.6%) vs 12/67 low risk (17.9%) pts. A 2-month (mo) analysis of G3/4 HG risk confirmed decreased probability at lower risk scores (area under the curve: training set = 0.991, testing set = 0.767). In all pts in the ALP arm of SOLAR-1, the model found a higher incidence of all-G and G3/4 HG, use of multiple AHAs, and more dose mods and discs in the high vs low risk pts (Table). There was no difference in median PFS in high (11.0 mo) vs low risk (10.9 mo) pts in the ALP arm with PIK3CA mutations.

HG incidence and management, n (%) All Pts N = 284 High Risk N = 106 Low Risk N = 178
All-G HG 187 (65.8) 101 (95.3) 86 (48.3)
G3/4 HG 108 (38.0) 96 (90.6) 12 (6.7)
Patients who received AHAs 163 (57.4) 94 (88.7) 70 (39.3)
1 AHA 67 (41.1) 24 (25.5) 43 (61.4)
2 AHA 49 (30.1) 31 (33.0) 18 (25.7)
≥3 AHA 47 (28.8) 39 (41.5) 9 (12.9)
Dose mods for any reason (reductions and/or interruption of ALP) 213 (75.0) 92 (86.8) 122 (68.5)
Permanent discs for any reason 244 (85.9) 90 (84.9) 154 (86.5)
Discs due to HG 19 (6.7) 15 (14.2) 4 (2.2)

Conclusions

Risk modeling identified 5 baseline factors (FPG, BMI, HbA1c, monocyte counts, and age) associated with a higher probability of ALP-induced G3/4 HG. High risk pts had higher rates of AHAs and ALP mods. This model could be used clinically to identify pts at high risk for ALP-induced HG. Regardless of risk, pts with PIK3CA mutations derived a similar PFS benefit from ALP.

Clinical trial identification

NCT02437318, NCT01219699.

Editorial acknowledgement

This abstract was developed with editorial assistance provided by Daniele Cary, 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

J. Rodon: Honoraria (self), Advisory/Consultancy: Novartis, Eli Lilly, Orion Pharmaceuticals, Servier Pharmaceuticals, Peptomyc, Merck Sharp & Dohme, Kelun Pharmaceuticals/Klus Pharma, Spectrum Pharmaceuticals, Inc., Pfizer, Roche Pharmaceuticals, Ellipses Pharma, Certera, Bayer, Molecular Partners, Nov; Research grant/Funding (institution): Bayer, Novartis, Blueprint Pharmaceuticals, Spectrum Pharmaceuticals, Tocagen, Symphogen, BioAlta, Pfizer, GenMab, CytomX, Kelun-Biotech, Takeda-Millenium, GlaxoSmithKline, Ipsen; Travel/Accommodation/Expenses: ESMO, Department of Defense, Merck Sharp & Dohme, Louisiana State University, Kelun Pharmaceuticals/Klus Pharma, Huntsman Cancer Institute, Cancer Core Europe, Karolinska Cancer Institute, King Abdullah International Medical Research Center, Bayer, WIN Co; Non-remunerated activity/ies: European Journal of Cancer, VHIO/Ministero De Empleo Y Seguridad Social, Chinese University of Hong Kong, SOLTI, Elsevier, GlaxoSmithKline. D. Demanse: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis. H.S. Rugo: Research grant/Funding (institution): Plexxikon; Research grant/Funding (institution): Macrogenics; Research grant/Funding (institution), Travel/Accommodation/Expenses: OBI Pharma; Research grant/Funding (institution): Eisai; Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): GlaxoSmithKline; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Celsion; Research grant/Funding (institution): Merck; Travel/Accommodation/Expenses: Roche/Genentech; Travel/Accommodation/Expenses: Bayer. F. André: Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Roche. I. Mayer: Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Genentech; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Lilly; Honoraria (self), Advisory/Consultancy: Puma; Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self), Advisory/Consultancy: Immunomedics; Honoraria (self), Advisory/Consultancy: Macrogenics; Honoraria (self), Advisory/Consultancy: Seattle Genetics; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: GlaxoSmithKline; Honoraria (self), Advisory/Consultancy: Cylacel. H. Burris: Honoraria (institution), Research grant/Funding (institution): AstraZeneca, Incyte, Novartis, Bayer, Pfizer; Honoraria (institution): FORMA Therapeutics, Celgene, Daiichi Sankyo, HCA Healthcare/Sarah Cannon, GRAIL; Research grant/Funding (institution): Roche/Genentech, Bristol-Myers Squibb, MedImmune, Macrogenics, Boehringer Ingelheim, Lilly, Seattle Genetics, Merck, Agios, Jounce Therapeutics, Moderna, CytomX, GlaxoSmithKline, Verastern, Tesaro, BioMed Valley Discoveries, TG Therapeutics, Vertex, eFFEC. A. Farooki: Leadership role: Novartis. H. Hu, I. Lorenzo, C. Quadt: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis. D. Juric: Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Genentech; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self), Advisory/Consultancy: Ipsen; Honoraria (self), Advisory/Consultancy: EMD Serono. All other authors have declared no conflicts of interest.

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Presenter Of 1 Presentation

 Conference Calendar
Proffered Paper session 1 Proffered paper

Invited Discussant 63O and 91O (ID 241)

Lecture Time
14:36 - 14:46
Speakers
Session Name
Proffered Paper session 1
Room
Channel 2
Date
Fri, 07.05.2021
Time
14:15 - 15:30

Author Of 1 Presentation

 On-Demand ePoster Display

100P - Efficacy of Enobosarm, a selective androgen receptor (AR) targeting agent, in patients with metastatic AR+/ER+ breast cancer resistant to estrogen receptor targeted agents and CDK 4/6 inhibitor in a Phase 2 clinical study

Abstract

Background

CDK 4/6 inhibitors (CDK4/6i) in combination with an ER targeted agent are the standard of care in in the treatment of metastatic ER+ breast cancer (MBC). Despite the significant increase in progression free survival seen with this combination, all patients eventually progress and therefore, there is a need for additional therapeutic options. The AR is expressed in up to 90% of ER+ breast cancer where it acts as a tumor suppressor. Enobosarm is a selective AR activating agent that does not cause virilization, and has positive clinical attributes such as promotion of bone strength and improvement of physical function. We report the clinical activity of enobosarm post CDK4/6i in women with AR+/ER MBC.

Methods

In study G200802, women with heavily pretreated AR+/ER+ MBC were randomized to receive either 9 mg (n=72) or 18 mg (n=64) of oral daily enobosarm. The safety and clear clinical activity of enobosarm in this study has previously been reported (Palmieri et al., 2020). In this analysis, the antitumor activity of targeting AR in women previously treated with and progressing on a CDK 4/6i in study G200802 was examined.

Results

There were 10 evaluable patients with measurable metastatic AR+/ER+ MBC who had progressed following treatment with a CDK 4/6i (palbociclib). Enobosarm, dosed at either 9mg or 18 mg oral daily, resulted in a clinical benefit rate of 60%, and the best objective tumor response was 33% including 2 CRs and 1 PR. The overall mean radiographic PFS in the 9 mg cohort was 10.6 months and the median was 5.2 months. Enobosarm was well tolerated.

Conclusions

We report clinical activity of enobosarm in patients with AR+/ER+ MBC with prior disease progression on ER directed therapy plus palbociclib. At the 9 mg dose, which has been selected for the phase III study, the mean rPFS was 10.6 months. These data provide support for exploring the potential clinical benefit of targeting AR with enobosarm in MBC that has progressed on a CDK4/6 inhibitor. The phase III, ARTEST trial will commence in the Q2 2021 in patients with AR+/ER+/HER2- metastatic breast cancer that has progressed on a non-steroidal aromatase inhibitor, fulvestrant and CDK 4/6 inhibitor.

Clinical trial identification

NCT02463032.

Legal entity responsible for the study

GTx performed the study and Veru Inc performed the data analysis.

Funding

GTx funded the clinical trial and Veru Inc supported the data analysis.

Disclosure

C. Vogel, J. O'Shaughnessy, A.M. Brufsky: Advisory/Consultancy: Veru Inc. R.H. Getzenberg: Shareholder/Stockholder/Stock options, Full/Part-time employment: Veru Inc. K.G. Barnette, M. Steiner: Shareholder/Stockholder/Stock options, Full/Part-time employment, Officer/Board of Directors: Veru Inc. All other authors have declared no conflicts of interest.

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