Publications

Gedatolisib

Clinical Cancer Research

2025
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Gedatolisib combined with palbociclib and letrozole in patients with no prior systemic therapy for hormone receptor–positive, HER2-negative advanced breast cancer
Robert Wesolowski, Hope S. Rugo, Jennifer M. Specht, Hyo S. Han, Peter Kabos, Ulka Vaishampayan, Seth A. Wander, Keerthi Gogineni, Alexander Spira, Anne F. Schott, Maysa Abu-Khalaf, Sarah C. Mutka, Samuel Suzuki, Brian Sullivan, Igor Gorbatchevsky, and Rachel M. Layman

The Lancet Oncology

2025
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Overall survival in patients with HR+/HER2- advanced breast cancer treated in a phase 1b trial evaluating gedatolisib in combination with palbociclib and endocrine therapy
Hope S. Rugo, Robert Wesolowski, Hyo Han, Jennifer M. Specht, E. Claire Dees, Erica M. Stringer-Reasor, Peter Kabos, Vandana Abramson, Amy Weise, Anne Schott, Maysa Abu-Khalaf, Keerthi Gogineni, Alexander Spira, Charlotte Moser, Nadene Zack, Samuel Suzuki, Sarah Mutka, Brian Sullivan, Igor Gorbatchevsky, Rachel M. Layman

International Journal of Molecular Sciences

2025
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Functional analysis of the PI3K/AKT/mTOR pathway inhibitor, gedatolisib, plus fulvestrant with and without palbociclib in breast cancer models
Aaron Broege, Stefano Rossetti, Adrish Sen, Ann De La Forest, Laura Davis, Megan Seibel, Arul Menon, Syndey Stokke, Allison Macaulay, Jhomary Molden, Lance Laing

2024 San Antonio Breast Cancer Symposium (SABCS)

2024
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Overall survival in patients with HR+/HER2- advanced breast cancer treated in a phase 1b trial evaluating gedatolisib in combination with palbociclib and endocrine therapy
Hope S. Rugo, Robert Wesolowski, Hyo Han, Jennifer M. Specht, E. Claire Dees, Erica M. Stringer-Reasor, Peter Kabos, Vandana Abramson, Amy Weise, Anne Schott, Maysa Abu-Khalaf, Keerthi Gogineni, Alexander Spira, Charlotte Moser, Nadene Zack, Samuel Suzuki, Sarah Mutka, Brian Sullivan, Igor Gorbatchevsky, Rachel M. Layman

2024 San Antonio Breast Cancer Symposium (SABCS)

2024
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Different effects of gedatolisib versus single-node PI3K/AKT/mTOR pathway inhibitors on breast cancer cell metabolic functions
Stefano Rossetti, Aaron Broege, Jhomary Molden, Ross Kopher, Stephen Schulz, Ky McCracken, Igor Gorbatchevsky, Brian Sullivan, Lance Laing

2024 San Antonio Breast Cancer Symposium (SABCS)

2024
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Mechanism of action of gedatolisib in combination with fulvestrant and/or palbociclib in estrogen receptor positive breast cancer models
Stefano Rossetti, Aaron Broege, Megan Seibel, Jhomary Molden, Igor Gorbatchevsky, Brian Sullivan, Lance Laing

Cancers

2024
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Functional Assessments of Gynecologic Cancer Models Highlight Differences Between Single-Node Inhibitors of the PI3K/AKT/mTOR Pathway and a Pan-PI3K/mTOR Inhibitor, Gedatolisib
Aaron Broege, Stefano Rossetti, Adrish Sen, Aurul Menon, Ian MacNeil, Jhomary Molden, and Lance Laing

Molecular Oncology

2024
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Assessments of prostate cancer cell functions highlight differences between a pan-PI3K/mTOR inhibitor, gedatolisib, and single-node inhibitors of the PI3K/AKT/mTOR pathway
Adrish Sen, Salmaan Khan, Stefano Rossetti , Aaron Broege, Ian MacNeil, Ann DeLaForest, Jhomary Molden, Laura Davis, Charles Iversrud, Megan Seibel, Ross Kopher, Stephen Schulz and Lance Laing

npj | Breast Cancer

2024
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Gedatolisib shows superior potency and efficacy versus single-node PI3K/AKT/mTOR inhibitors in breast cancer models
Stefano Rossetti, Aaron Broege, Adrish Sen, Salmaan Khan, Ian MacNeil, Jhomary Molden, Ross Kopher, Stephen Schulz & Lance Laing

The Lancet Oncology

2024
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Gedatolisib in combination with palbociclib and endocrine therapy in women with hormone receptor-positive, HER2-negative advanced breast cancer: results from the dose expansion groups of an open-label, phase 1b study
Rachel M Layman, Hyo S Han, Hope S Rugo, Erica M Stringer-Reasor, Jennifer M Specht, E Claire Dees, Peter Kabos, Samuel Suzuki, Sarah C Mutka, Brian F Sullivan, Igor Gorbatchevsky, Robert Wesolowski

2023 San Antonio Breast Cancer Symposium (SABCS)

2023
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Gedatolisib, a pan-PI3K/mTOR inhibitor, shows superior potency & efficacy relative to other PI3K/AKT/mTOR pathway inhibitors in breast cancer models
Stefano Rossetti, Aaron Broege, Adrish Sen, Salmaan Khan, Ian MacNeil, Jhomary Molden, Igor Gorbatchevsky, Brian Sullivan, Lance Laing

2023 ESMO Breast Cancer Annual Congress

2023
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Phase 1b study of gedatolisib plus palbociclib and endocrine therapy in women with hormone receptor positive advanced breast cancer: updated results in treatment naïve patients
Hope S. Rugo, Robert Wesolowski, Erica M. Stringer Reasor, Hyo Han, Jennifer M. Specht, E. Claire Dees, Peter Kabos, Ulka Vaishampayan, Seth A. Wander, Janice Lu, Keerthi Gogineni, Alexander Spira, Anne F. Schott, Maysa Abu Khalaf, Sarah C. Mutka, Samuel Suzuki, Igor Gorbatchevsky, Rachel M. Layman

2023 American Association for Cancer Research

2023
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Gedatolisib, a well-tolerated pan-PI3K/mTOR inhibitor, exhibits potent therapeutic effects on gynecological cancer models regardless of their PI3K pathway mutational status
Stefano Rossetti, Aaron Broege, Ian MacNeil, Ben Rich, Jhomary Molden, Brian Sullivan, Lance Laing

2023 American Association for Cancer Research

2023
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A Phase 3 study of gedatolisib plus fulvestrant with and without palbociclib in patients with HR+/HER2- advanced breast cancer previously treated with a CDK4/6 inhibitor plus a non-steroidal aromatase inhibitor (VIKTORIA-1)
Sara Hurvitz, Fabrice Andre, Massimo Cristofanilli, Giuseppe Curigliano, Antonio Giordano, Hyo Han, Miguel Martin, Barbara Pistilli, Hope Rugo, Robert Wesolowski, Samuel Suzuki, Sarah C. Mutka, Igor Gorbatchevsky, Sibylle Loibl

2023 ASCO Genitourinary (GU) Cancers Symposium

2023
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Therapeutic effect of gedatolisib, a pan-PI3K/mTOR inhibitor, on prostate cancer models differing in PI3K or PTEN mutational status
Adrish Sen, Salmaan A. Khan, Ian A. MacNeil, Benjamin E. Rich, Jhomary S. Molden, Laura N. Davis, Stefano Rossetti, Aaron M. Broege, Lance G. Laing

2022 San Antonio Breast Cancer Symposium (SABCS)

2022
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A Phase 3 study of gedatolisib plus fulvestrant with and without palbociclib in patients with HR+/HER2- advanced breast cancer previously treated with a CDK4/6 inhibitor plus a non-steroidal aromatase inhibitor (VIKTORIA-1)
Sara Hurvitz, Fabrice Andre, Massimo Cristofanilli, Giuseppe Curigliano, Antonio Giordano, Hyo Han, Miguel Martin, Barbara Pistilli, Hope Rugo, Robert Wesolowski, Samuel Suzuki, Sarah C. Mutka, Igor Gorbatchevsky, Sibylle Loibl

2022 San Antonio Breast Cancer Symposium (SABCS)

2022
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Updated results of a Phase 1b study of gedatolisib plus palbociclib and endocrine therapy in women with hormone receptor positive advanced breast cancer: Subgroup analysis by PIK3CA mutation status
Robert Wesolowski, Hope S. Rugo, Erica M. Stringer-Reasor, Hyo Han, Jennifer M. Specht, E. Claire Dees, Peter Kabos, Ulka Vaishampayan, Seth A. Wander, Janice Lu, Keerthi Gogineni, Alexander Spira, Anne F. Schott, Maysa Abu-Khalaf, Pratima Nayak, Brian F. Sullivan, Igor Gorbatchevsky, Rachel M. Layman

British Journal of Cancer

2022
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A Phase 1B open-label study of gedatolisib (PF-05212384) in combination with other anti-tumour agents for patients with advanced solid tumours and triple-negative breast cancer. British Journal of Cancer 2022
Giuseppe Curigliano, Geoffrey I. Shapiro, Rebecca S. Kristeleit, Albiruni R. Abdul Razak, Stephen Leong, Maria Alsina, Antonio Giordano, Karen A. Gelmon, Erica Stringer-Reasor, Ulka N. Vaishampayan, Mark Middleton, Anthony J. Olszanski, Hope S. Rugo, Kenneth A. Kern, Nuzhat Pathan, Rachelle Perea, Kristen J. Pierce, Sarah C. Mutka & Zev A. Wainberg

2021 San Antonio Breast Cancer Symposium (SABCS)

2021
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Phase II study of trastuzumab biosimilar (Herzuma®) plus gedatolisib in patients with HER-2 positive metastatic breast cancer who progressed after 2 or more HER-2 directed chemotherapy: KM-10A (KCSG BR 18-13) interim analysis
Ju Won Kim, Hee Kyung Ahn, Jong Gwon Choi, Yee Soo Chae, Gyeong-Won Lee, KeonUk Park, Eunmi Lee, Sung Hoon Sim, Jee Hyun Kim, Yeon Hee Park, Miso Ki1, Jin Hyun Park, Jeong Eun Kim, Han Jo Kim, Mi Sun Ahn, So Yeon Oh, Min Hwan Kim, Su-Jin Koh, Kyoung Eun Lee, Myoung Joo Kang, Jae Ho Byun, Joo young Ha, Jung Hye Kwon, Joo Young Jung, Su Ee Lee, Inhae Park, and Kyong Hwa Park

2021 San Antonio Breast Cancer Symposium (SABCS)

2021
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Phase Ib expansion study of gedatolisib in combination with palbociclib and endocrine therapy in women with ER+ metastatic breast cancer
Rachel M. Layman, Robert Wesolowski, Hyo Han, Jennifer M. Specht, Erica M. Stringer-Reasor, E. Claire Dees, Peter Kabos, Ingrid A. Mayer, Ulka Vaishampayan, Janice Lu, Keerthi Gogineni, Aditya Bardia, Anne F. Schott, Maysa M. Abu-Khalaf, Doug Hawkins, Brian Sullivan, Igor Gorbatchevsky, Hope S. Rugo

Clinical Cancer Research

2021
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Phase I dose-escalation study of the dual PI3K-mTORC1/2 inhibitor gedatolisib in combination with paclitaxel and carboplatin in patients with advanced solid tumors. Clin Cancer Res;27:5012–9, 2021
Ilaria Colombo, Sofia Genta, Federica Martorana, Monia Guidi, Milo Frattini, Eleftherios Pierre Samartzis, Simone Brandt, Sheila Gaggetta, Laura Moser, Mariarosa Pascale, Tatiana Terrot, Cristiana Sessa, and Anastasios Stathis

2021 American Association of Cancer Research (AACR)

2021
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Subgroup of HER2-negative breast cancer patients with hyperactive RAS network signaling identified: dynamic pathway activity test identifies patients that may benefit from PI3K/mTOR or PI3K/mTOR/BCL inhibitors
Salmaan Khan, Adrish Sen, Catherine Kuzmicki, Ian MacNeil, Aaron Broege, Sarah Mutka, Kelly Brass, Ky McCracken, Laura Milligan, Kaija Kottke, Brian Sullivan, Lance G. Laing

2021 American Association of Cancer Research (AACR)

2021
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Subgroup of ovarian cancer patients with hyperactive RAS network signaling identified: dynamic pathway activity test identifies patients that may benefit from PI3K/mTOR or PI3K/mTOR/BCL inhibitors
Stefano Rossetti, Aaron Broege, Joanna Sabat, Shu Wiley, Salmaan Khan, Catherine Kuzmicki, Ian MacNeil, Brian Sullivan, Lance Laing

Gynecologic Oncology

2021
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A randomized phase II non-comparative study of PF-04691502 and gedatolisib (PF-05212384) in patients with recurrent endometrial cancer, Gynecologic Oncology 142, 62–69, 2016
Josep María del Campo, Michael Birrer, Craig Davis, Keiichi Fujiwara, Ashwin Gollerkeri, Martin Gore, Brett Houk, Susie Lau, Andres Poveda, Antonio González-Martín, Carolyn Muller, Kei Muro, Kristen Pierce, Mie Suzuki, Jennifer Vermette, Amit Oza

Clinical Cancer Research

2015
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First-in human study of PF-05212384 (PKI-587), a small-molecule, intravenous, dual inhibitor of PI3K and mTOR in patients with advanced cancer. Clin Cancer Res; 21(8) April 15, 2015
Geoffrey I. Shapiro, Katherine M. Bell-McGuinn, Julian R. Molina, Johanna Bendell, James Spicer, Eunice L. Kwak, Susan S. Pandya, Robert Millham, Gary Borzillo, Kristen J. Pierce, Lixin Han, Brett E. Houk, Jorge D. Gallo, Maria Alsina, Irene Brana, and Josep Tabernero

Clinical Cancer Research

2011
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Antitumor Efficacy of PKI-587, a Highly Potent Dual PI3K/mTOR Kinase Inhibitor, Clin Cancer Res; 17(10); 3193–203, 2011
Robert Mallon, Larry R. Feldberg, Judy Lucas, Inder Chaudhary, Christoph Dehnhardt, Efren Delos Santos, Zecheng Chen, Osvaldo dos Santos, Semiramis Ayral-Kaloustian, Aranapakam Venkatesan, and Irwin Hollander

Journal of Medicinal Chemistry

2010
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Bis(morpholino-1,3,5-triazine) Derivatives: Potent Adenosine 50-Triphosphate Competitive Phosphatidylinositol-3-kinase/Mammalian Target of Rapamycin Inhibitors: Discovery of Compound 26 (PKI-587), a Highly Efficacious Dual Inhibitor. J. Med. Chem. 2010, 53, 6, 2636–2645
Aranapakam M Venkatesan, Christoph M Dehnhardt, Efren Delos Santos, Zecheng Chen, Osvaldo Dos Santos, Semiramis Ayral-Kaloustian, Gulnaz Khafizova, Natasja Brooijmans, Robert Mallon, Irwin Hollander, Larry Feldberg, Judy Lucas, Ker Yu, James Gibbons, Robert T Abraham, Inder Chaudhary, Tarek S Mansour

CELSignia

Cell Communication and Signaling

2022
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Functional signaling test identifies HER2 negative breast cancer patients who may benefit from c-Met and pan-HER combination therapy. Cell Communication and Signaling, 20:4, 2022
Ian A. MacNeil, Salmaan A. Khan, Adrish Sen, Sajjad M. Soltani, David J. Burns, Brian F. Sullivan & Lance G. Laing

Journal of Cancer Research and Clinical Oncology

2020
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New HER2‐negative breast cancer subtype responsive to anti‐HER2 therapy identified. Journal of Cancer Research and Clinical Oncology 2020;146:605-619
Ian A. MacNeil, David J. Burns, Benjamin E. Rich, Sajjad M. Soltani, Samantha Kharbush, Nicole G. Osterhaus, Brian F. Sullivan, Douglas M. Hawkins, Jodie R. Pietruska, Lance G. Laing

2020 American Association of Cancer Research (AACR)

2020
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Hyperactive c-Met and ErbB signaling detected in a sub-group of ovarian patient tumors: Patient sub-group may benefit from c-Met and pan-HER combination therapy
Stefano Rossetti, Catherine Kuzmicki, Aaron Broege, Joanna Sabat, Salmaan Khan, Ian MacNeil, Brian Sullivan, Lance Laing

2020 American Society of Clinical Oncology (ASCO)

2020
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Test measuring signaling activity in live patient tumor cells identifies PI3KCA WT patients who may benefit from PIK3 inhibitors
Lance G Laing, Salmaan Khan, Ian A MacNeil, Catherine Kuzmicki, Benjamin Rich, Abhay Shukla, Kelly Brass, Brian Sullivan

2019 San Antonio Breast Cancer Symposium (SABCS)

2019
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Sub-Group of PIK3CA WT breast cancer patients have hyperactive S1P and LPA signaling tumors responsive to PI3K inhibitors: functional signaling test identifies new patient group who may benefit from PI3K inhibitors
Lance G Laing, Salmaan Khan, Ian A MacNeil, Catherine Kuzmicki, Samantha Kharbush, Benjamin Rich, Abhay Shukla, Kelly Brass, Brian Sullivan

2018 San Antonio Breast Cancer Symposium (SABCS)

2018
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Evaluation of pan-HER and c-MET inhibitors tested ex vivo in live primary HER2- breast cancer cells with hyperactive c-MET and ErbB family signaling
Laing, L., Burns, D., Khan, S., MacNeil, I., Rich, B., Soltani, S., Myhre, S., Kharbush, S., Broege, AM., Brass, K., Mutka, S., Sullivan. B

2018 San Antonio Breast Cancer Symposium (SABCS)

2018
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Evaluating contribution of hyperactive c-Met and ErbB signaling to tumor progression in mouse breast tumor xenografts: an in vivo study of c-Met and ErbB targeted therapies
Laing, L., Burns, D., Khan, S., MacNeil, I., Rich, B., Soltani, S., Myhre, S., Kharbush, S., Brass, K., Sullivan. B

2018 San Antonio Breast Cancer Symposium (SABCS)

2018
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Sub-group of HER2- breast cancer patients with hyperactive and co-involved c-Met and ErbB pathways identified: functional signal profiling test identifies patient group that may benefit from c-Met and pan-HER combination therapy
Laing, L., Burns, D., Khan, S., MacNeil, I., Rich, B., Soltani, S., Myhre, S., Kharbush, S., Brass, K., Broege, AM., Mutka, S., Sullivan. B

2018 American Society of Clinical Oncology (ASCO)

2018
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Live tumor cell functional analysis and a xenograft model find co-activated c-Met and ErbB signaling in HER2-negative breast cancer
Lance G Laing, David J Burns, Salmaan Khan, Ian A MacNeil, Benjamin E Rich, Sajjad M. Soltani, Samantha Myhre, Brian F Sullivan

2018 Miami Breast Cancer Conference

2018
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A phase 2 study of neoadjuvant chemotherapy plus trastuzumab and pertuzumab in HER2-negative breast cancer patients with abnormal HER2-driven signaling transduction (NCT03412643)
Eleftherios P. Mamounas, MD, MPH; Lance G Laing

Oncotarget

2017
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A functional signal profiling test for identifying a subset of HER2-negative breast cancers with abnormal amplified HER2 signaling activity. Oncotarget. 2016 Oct 5;7(48) 78577-78590
Huang, Y., Burns, D., Rich, B., MacNeil, I., Dandapat, A., Soltani, S., Myhre, S., Sullivan, B., Furcht, L., Lange, C., Hurvitz, S., & Laing, L.

2017 American Society of Clinical Oncology (ASCO)

2017
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Measuring functional HER2-driven signaling status ex vivo to predict response to HER2 therapy: Results from a mouse breast tumor xenograft study
Laing, L., Burns, D., Huang, Y., MacNeil, I., Rich, B., Soltani, S., Myhre, S., Sullivan, B.

BMC Cancer

2017
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Development of a test that measures real-time HER2 signaling activity in live breast cancer cell lines and primary cells. BMC Cancer. 2017 March 17:199
Huang, Y., Burns, D., Rich, B., MacNeil, I., Dandapat, A., Soltani, S., Myhre, S., Sullivan, B., Lange, C., Furcht, L., Laing, L.

2017 San Antonio Breast Cancer Symposium (SABCS)

2017
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Use of a functional signal profiling test to determine the prevalence of abnormal HER2-driven signaling activity in the HER2-negative breast cancer patient population: New patient group may benefit from anti-HER2 therapy
Lance G Laing, David J Burns, Ian A MacNeil, Benjamin E Rich, Sajjad M Soltani, Samantha Myhre, Brian F Sullivan

2017 Miami Breast Cancer Conference

2017
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Inhibition of abnormal HER2-driven signaling by two HER2 targeted antibody drugs tested ex vivo in live primary HER2- breast cancer cell samples and HER2+ cell lines

2016 San Antonio Breast Cancer Symposium (SABCS)

2016
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Quantification of HER2-driven signaling (HER2S) inhibition of four different anti-HER2 drugs tested ex vivo in live primary HER2-negative breast cancer cell samples with abnormal HER2 signaling activity
Laing, L., Burns, D., Huang, Y., MacNeil, I., Rich, B., Soltani, S., Myhre, S., Sullivan, B.

2016 San Antonio Breast Cancer Symposium (SABCS)

2016
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New method to measure functional HER2-driven signaling activity in primary tumor cells identifies HER2-negative breast cancers with abnormal HER2 signaling activity: New group of patients may benefit from anti-HER2 therapy
Laing, L., Burns, D., Huang, Y., MacNeil, I., Rich, B., Soltani, S., Myhre, S., Sullivan, B.

2014 American Society of Clinical Oncology (ASCO)

2014
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Profiling of signaling pathways in live tumor cells to assess drug mechanism of action: A method to predict drug efficacy in a patient
Laing, L., Huang, Y., MacNeil, I., Rich, B., Greeno, E.

2014 American Society of Clinical Oncology (ASCO)

2014
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Dynamic real-time signaling profiles of live primary cells characterize the response of PI3K and MAPK pathways in HER2+ breast cancer cells to attenuation with lapatinib: Tests of reproducibility of method
Laing, L., Huang, Y., MacNeil, I., Rich, B., Greeno, E.