Abstract
ABI-009 (nab-sirolimus) in advanced malignant perivascular epithelioid cell tumors (PEComa): Preliminary efficacy, safety, and mutational status from AMPECT, an open label phase II registration trial.
Author
person
Andrew J. Wagner
Dana-Farber Cancer Institute, Boston, MA
info_outline
Andrew J. Wagner, Vinod Ravi, Kristen N. Ganjoo, Brian Andrew Van Tine, Richard F. Riedel, Rashmi Chugh, Lee D. Cranmer, Erlinda Maria Gordon, Jason L. Hornick, David J. Kwiatkowski, Heng Du, Berta Grigorian, Anita N. Schmid, Shihe Hou, Katherine Harris, Neil Desai, Mark Andrew Dickson
Full text
Authors
person
Andrew J. Wagner
Dana-Farber Cancer Institute, Boston, MA
info_outline
Andrew J. Wagner, Vinod Ravi, Kristen N. Ganjoo, Brian Andrew Van Tine, Richard F. Riedel, Rashmi Chugh, Lee D. Cranmer, Erlinda Maria Gordon, Jason L. Hornick, David J. Kwiatkowski, Heng Du, Berta Grigorian, Anita N. Schmid, Shihe Hou, Katherine Harris, Neil Desai, Mark Andrew Dickson
Organizations
Dana-Farber Cancer Institute, Boston, MA, The University of Texas MD Anderson Cancer Center, Department of Sarcoma Medical Oncology, Houston, TX, Stanford Cancer Institute, Stanford, CA, Washington University in St. Louis, St. Louis, MO, Duke University Medical Center, Durham, NC, University of Michigan, Ann Arbor, MI, University of Washington/Fred Hutchinson Cancer Research Center, Seattle, WA, Sarcoma Oncology Research Center, Santa Monica, CA, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, Aadi Bioscience, Pacific Palisades, CA, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
Abstract Disclosures
Research Funding
Pharmaceutical/Biotech Company
Other Government Agency, FDA office of orphan drug development (FD005749)
Background:
Malignant PEComa is a rare, aggressive sarcoma, with no approved treatment or prior clinical trials. Case reports suggest mTOR activation through mutations or deletions of
TSC1
or
TSC2
and activity of mTOR inhibitors in this disease. ABI-009 is an albumin-bound mTOR inhibitor with increased tumor uptake. The AMPECT trial is the first prospective study in malignant PEComa.
Methods:
Eligible patients (pts) with centrally confirmed PEComa receive ABI-009 (100 mg/m
2
IV, wkly, 2/3 wks) until progression or unacceptable toxicity. Primary endpoint: ORR by independent review (IR), assessed every 6 wks (RECIST v1.1). Secondary endpoints: duration of response (DOR), PFS6, PFS, and safety. Exploratory endpoints (EE): investigator-assessed (IA) outcomes and mutational status. Sample size: 30 efficacy-evaluable pts based on target ORR of 30% (primary analysis planned when all pts treated ≥6 mo).
Results:
EE and safety are reported (IR pending). As of Feb 12, 2019, enrollment is complete; 34 pts treated, 31 evaluable for efficacy, 42% (13/31) pts ongoing Rx. IA ORR is 42% PR (13/31, 95% CI: 24.5, 60.9), 35% SD (11/31), and 23% PD (7/31); 69% of PRs were reached at 1st restaging (wk 6); 69% PRs are ongoing, with 5 pts >1yr and 2 pt >2 yrs on Rx (all ongoing). Other IA outcomes: median DOR is not reached; PFS6 is 66%; median PFS is 8.9 mo (95% CI: 5.5, -). The most common (>30%) nonhematologic treatment-related AEs (TRAEs) of any grade: mucositis (65%), fatigue (53%), nausea/weight loss (35% each), diarrhea (32%); the most common (>15%) hematologic TRAEs: anemia (44%) and thrombocytopenia (18%). Pneumonitis (15%) was G1/G2. The most common (>10%) G3 TRAEs: mucositis (18%), anemia (12%); No grade ≥4 TRAEs.
TSC1
or
TSC2
mutations occurred in 5 and 9 (no overlap) of 25 pts with known mutational status, respectively. PR was seen in 100% (9/9) pts with
TSC2
mutation, 20% (1/5) pts with
TSC1
mutation, and 9% (1/11) pts without mutation in
TSC1
or
TSC2
,
P
< 0.0001 (2x3 Fisher exact test). PR was significantly higher in pts with
TSC2
mutations vs pts without mutation in
TSC1
or
TSC2,
P
= 0.0001 (Fisher exact test). Disease control (PR+SD) was seen in 93% (13/14) pts with
TSC1 or TSC2
mutations vs 55% (6/11) pts without mutation in
TSC1
or
TSC2
,
P
= NS.
Conclusions:
Preliminary IA outcomes showed that ABI-009 treatment of PEComa resulted in substantial and durable responses with manageable toxicities.
TSC2
mutations were associated with IA response. Clinical trial information:
NCT02494570