A Phase Ib Expansion Cohort Evaluating Aurora A Kinase Inhibitor Alisertib and Dual TORC1/2 Inhibitor Sapanisertib in Patients with Advanced Solid Tumors
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patient Selection
2.2. Study Design
2.3. Correlative Studies
2.3.1. Functional Imaging
2.3.2. Tumor Tissue Evaluation
Fluorescence Microscopy
SA-β-Gal and H and E
2.4. Statistical Methods
3. Results
3.1. Clinical Outcomes
3.1.1. Solid Tumor Expansion Cohort
3.1.2. Pancreatic Cancer Expansion Cohort
3.2. Toxicities
3.3. Correlative Studies
3.3.1. Functional Imaging
3.3.2. Tumor Tissue Analysis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Number of Patients (%) | |||
---|---|---|---|
Characteristic | Alisertib Lead-In (n = 10) Patients A-1 through A-10 | Sapanisertib Lead-In (n = 10) Patients S-1 through S-10 | Pancreatic Cancer Expansion (n = 11) Patients P-1 through P-11 |
Age | |||
Median (Range) | 59 (51–71) | 63 (39–74) | 56 (38–74) |
Sex | |||
Male | 2 (20%) | 4 (40%) | 9 (82%) |
Female | 8 (80%) | 6 (60%) | 2 (18%) |
Race/Ethnicity | |||
Caucasian | 9 (90%) | 7 (70%) | 7 (64%) |
Hispanic | 1 (10%) | 1 (10%) | 3 (27%) |
African American | 0 (0%) | 1 (10%) | 1 (9%) |
Asian | 0 (0%) | 1 (10%) | 0 (0%) |
Tumor type | |||
Breast adenocarcinoma | 5 (50%) | 4 (40%) | 0 (0%) |
Colorectal adenocarcinoma | 2 (20%) | 2 (20%) | 0 (0%) |
Ovarian serous carcinoma | 2 (20%) | 1 (0%) | 0 (0%) |
Pancreatic adenocarcinoma | 1 (10%) | 2 (20%) | 11 (100%) |
Uterine serous carcinoma | 0 (0%) | 1 (10%) | 0 (0%) |
Renal cell carcinoma | 0 (0%) | 1 (10%) | 0 (0%) |
Baseline ECOG Performance Status | |||
0 | 2 (20%) | 3 (30%) | 4 (36%) |
1 | 8 (80%) | 7 (70%) | 7 (64%) |
Prior Lines of Therapy for Metastatic Disease | |||
Median (Range) | 4 (3–14) | 3 (2–9) | 2 (1–3) |
1 | 0 (0%) | 0 (0%) | 1 (9%) |
2 | 0 (0%) | 3 (30%) | 7 (64%) |
3 | 2 (20%) | 3 (30%) | 3 (27%) |
4 | 4 (40%) | 0 (0%) | 0 (0%) |
5 or more | 4 (40%) | 4 (40%) | 0 (0%) |
Alisertib Lead-In N = 10 | Sapanisertib Lead-In N = 10 | Pancreatic Cancer Expansion N = 11 | All Treatment Groups N = 31 | ||||||
---|---|---|---|---|---|---|---|---|---|
Number (percent) | Grade 1/2 | Grade 3/4 | Grade 1/2 | Grade 3/4 | Grade 1/2 | Grade 3/4 | Grade 1/2 | Grade 3/4 | Total |
Fatigue | 3 | 1 | 7 | 0 | 7 | 0 | 17 (55%) | 1 (3%) | 18 (58%) |
Diarrhea | 3 | 1 | 2 | 0 | 6 | 1 | 11 (35%) | 2 (6%) | 13 (42%) |
Nausea | 2 | 0 | 4 | 0 | 7 | 0 | 13 (42%) | 0 | 13 (42%) |
Abdominal pain | 2 | 1 | 2 | 0 | 3 | 2 | 7 (23%) | 3 (10%) | 10 (32%) |
Mucositis | 3 | 2 | 2 | 0 | 1 | 1 | 6 (19%) | 3 (10%) | 9 (29%) |
Hyperglycemia | 2 | 1 | 2 | 0 | 3 | 0 | 7 (23%) | 1 (3%) | 8 (26%) |
Anorexia | 2 | 0 | 2 | 0 | 4 | 0 | 8 (26%) | 0 | 8 (26%) |
Hypokalemia | 2 | 0 | 0 | 0 | 4 | 1 | 6 (19%) | 1 (3%) | 7 (23%) |
Neutropenia | 0 | 1 | 2 | 0 | 0 | 3 | 2 (6%) | 4 (13%) | 6 (20%) |
Cognitive disturbance | 0 | 0 | 2 | 1 | 3 | 0 | 5 (16%) | 1 (3%) | 6 (20%) |
Dyspnea | 3 | 0 | 0 | 1 | 2 | 0 | 5 (16%) | 1 (3%) | 6 (20%) |
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Davis, S.L.; Messersmith, W.A.; Purcell, W.T.; Lam, E.T.; Corr, B.R.; Leal, A.D.; Lieu, C.H.; O’Bryant, C.L.; Smoots, S.G.; Dus, E.D.; et al. A Phase Ib Expansion Cohort Evaluating Aurora A Kinase Inhibitor Alisertib and Dual TORC1/2 Inhibitor Sapanisertib in Patients with Advanced Solid Tumors. Cancers 2024, 16, 1456. https://doi.org/10.3390/cancers16081456
Davis SL, Messersmith WA, Purcell WT, Lam ET, Corr BR, Leal AD, Lieu CH, O’Bryant CL, Smoots SG, Dus ED, et al. A Phase Ib Expansion Cohort Evaluating Aurora A Kinase Inhibitor Alisertib and Dual TORC1/2 Inhibitor Sapanisertib in Patients with Advanced Solid Tumors. Cancers. 2024; 16(8):1456. https://doi.org/10.3390/cancers16081456
Chicago/Turabian StyleDavis, S. Lindsey, Wells A. Messersmith, W. Thomas Purcell, Elaine T. Lam, Bradley R. Corr, Alexis D. Leal, Christopher H. Lieu, Cindy L. O’Bryant, Stephen G. Smoots, Evan D. Dus, and et al. 2024. "A Phase Ib Expansion Cohort Evaluating Aurora A Kinase Inhibitor Alisertib and Dual TORC1/2 Inhibitor Sapanisertib in Patients with Advanced Solid Tumors" Cancers 16, no. 8: 1456. https://doi.org/10.3390/cancers16081456