Abstract
Objective. To examine the tolerability and antitumor activity of trebananib plus pegylated liposomal doxorubicin (PLD) or topotecan in recurrent platinum-resistant or partially platinum-sensitive ovarian cancer.
Methods. In this open-label phase 1b study, patients received trebananib 10 mg/kg or 15 mg/kg IV QWplus PLD 50 mg/m2 (cohorts A1 and A3, respectively) or topotecan 4 mg/m2 (cohorts B1 and B3, respectively). Endpoints were dose-limiting toxicity (DLT; primary); treatment-emergent adverse events (AEs), overall response rate, anti-trebananib antibodies, and pharmacokinetics (secondary).
Results. 103 patients were enrolled. One patient in A1 and B1 had DLTs. Across all cohorts, themost common AEs were nausea, fatigue, and peripheral edema. Across both trebananib plus PLD cohorts (A1/A3), grade 4 AEs were pulmonary embolism, disease progression, and anemia. Two patients had grade 5 intestinal perforation (n = 1) and sudden death (n = 1). Across both trebananib plus topotecan cohorts (B1/B3), grade 4 AEs were neutropenia, hypokalemia, decreased granulocyte count, chest pain, dyspnea, decreased neutrophil count, and pulmonary embolism. Two patients had grade 5 disease progression. One patient had grade 5 pleural effusion associated with progressive disease. Confirmed objective response rates were 36.0% (A1), 34.8% (A3), 16.7% (B1), and 0.0% (B3). Median progression-free survival duration (months) was 7.4 (A1), 7.1 (A3), 3.5 (B1), and 3.1 (B3), respectively. No drug-drug interactions were apparent.
Conclusions. Trebananib 10 mg/kg and 15 mg/kg IV QWplus PLD or topotecan appear to have acceptable toxicity profiles in recurrent platinum-resistant or partially platinum-sensitive ovarian cancer. Antitumor activity was evident across all cohorts.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 25-33 |
| Number of pages | 9 |
| Journal | Gynecologic Oncology |
| Volume | 135 |
| Issue number | 1 |
| DOIs | |
| State | Published - Oct 1 2014 |
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Keywords
- Angiogenesis
- Angiopoietins
- Combination treatments
- Dose-limiting toxicities
- Targeted therapy
- Tie2 receptor
ASJC Scopus subject areas
- Obstetrics and Gynecology
- Oncology
- Medicine(all)
Cite this
A phase 1b study of trebananib in combination with pegylated liposomal doxorubicin or topotecan in women with recurrent platinum-resistant or partially platinum-sensitive ovarian cancer. / Vergote, Ignace; Schilder, Russell J.; Pippitt, Charles H.; Wong, Shirley; Gordon, Alan N.; Scudder, Sidney A; Kridelka, Frederic; Dirix, Luc; Leach, Joseph W.; Ananda, Sumitra; Nanayakkara, Nuwan; Melara, Rebeca; Bass, Michael B.; Litten, Jason; Adewoye, Henry; Wenham, Robert M.
In: Gynecologic Oncology, Vol. 135, No. 1, 01.10.2014, p. 25-33.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A phase 1b study of trebananib in combination with pegylated liposomal doxorubicin or topotecan in women with recurrent platinum-resistant or partially platinum-sensitive ovarian cancer
AU - Vergote, Ignace
AU - Schilder, Russell J.
AU - Pippitt, Charles H.
AU - Wong, Shirley
AU - Gordon, Alan N.
AU - Scudder, Sidney A
AU - Kridelka, Frederic
AU - Dirix, Luc
AU - Leach, Joseph W.
AU - Ananda, Sumitra
AU - Nanayakkara, Nuwan
AU - Melara, Rebeca
AU - Bass, Michael B.
AU - Litten, Jason
AU - Adewoye, Henry
AU - Wenham, Robert M.
PY - 2014/10/1
Y1 - 2014/10/1
N2 - Objective. To examine the tolerability and antitumor activity of trebananib plus pegylated liposomal doxorubicin (PLD) or topotecan in recurrent platinum-resistant or partially platinum-sensitive ovarian cancer.Methods. In this open-label phase 1b study, patients received trebananib 10 mg/kg or 15 mg/kg IV QWplus PLD 50 mg/m2 (cohorts A1 and A3, respectively) or topotecan 4 mg/m2 (cohorts B1 and B3, respectively). Endpoints were dose-limiting toxicity (DLT; primary); treatment-emergent adverse events (AEs), overall response rate, anti-trebananib antibodies, and pharmacokinetics (secondary).Results. 103 patients were enrolled. One patient in A1 and B1 had DLTs. Across all cohorts, themost common AEs were nausea, fatigue, and peripheral edema. Across both trebananib plus PLD cohorts (A1/A3), grade 4 AEs were pulmonary embolism, disease progression, and anemia. Two patients had grade 5 intestinal perforation (n = 1) and sudden death (n = 1). Across both trebananib plus topotecan cohorts (B1/B3), grade 4 AEs were neutropenia, hypokalemia, decreased granulocyte count, chest pain, dyspnea, decreased neutrophil count, and pulmonary embolism. Two patients had grade 5 disease progression. One patient had grade 5 pleural effusion associated with progressive disease. Confirmed objective response rates were 36.0% (A1), 34.8% (A3), 16.7% (B1), and 0.0% (B3). Median progression-free survival duration (months) was 7.4 (A1), 7.1 (A3), 3.5 (B1), and 3.1 (B3), respectively. No drug-drug interactions were apparent.Conclusions. Trebananib 10 mg/kg and 15 mg/kg IV QWplus PLD or topotecan appear to have acceptable toxicity profiles in recurrent platinum-resistant or partially platinum-sensitive ovarian cancer. Antitumor activity was evident across all cohorts.
AB - Objective. To examine the tolerability and antitumor activity of trebananib plus pegylated liposomal doxorubicin (PLD) or topotecan in recurrent platinum-resistant or partially platinum-sensitive ovarian cancer.Methods. In this open-label phase 1b study, patients received trebananib 10 mg/kg or 15 mg/kg IV QWplus PLD 50 mg/m2 (cohorts A1 and A3, respectively) or topotecan 4 mg/m2 (cohorts B1 and B3, respectively). Endpoints were dose-limiting toxicity (DLT; primary); treatment-emergent adverse events (AEs), overall response rate, anti-trebananib antibodies, and pharmacokinetics (secondary).Results. 103 patients were enrolled. One patient in A1 and B1 had DLTs. Across all cohorts, themost common AEs were nausea, fatigue, and peripheral edema. Across both trebananib plus PLD cohorts (A1/A3), grade 4 AEs were pulmonary embolism, disease progression, and anemia. Two patients had grade 5 intestinal perforation (n = 1) and sudden death (n = 1). Across both trebananib plus topotecan cohorts (B1/B3), grade 4 AEs were neutropenia, hypokalemia, decreased granulocyte count, chest pain, dyspnea, decreased neutrophil count, and pulmonary embolism. Two patients had grade 5 disease progression. One patient had grade 5 pleural effusion associated with progressive disease. Confirmed objective response rates were 36.0% (A1), 34.8% (A3), 16.7% (B1), and 0.0% (B3). Median progression-free survival duration (months) was 7.4 (A1), 7.1 (A3), 3.5 (B1), and 3.1 (B3), respectively. No drug-drug interactions were apparent.Conclusions. Trebananib 10 mg/kg and 15 mg/kg IV QWplus PLD or topotecan appear to have acceptable toxicity profiles in recurrent platinum-resistant or partially platinum-sensitive ovarian cancer. Antitumor activity was evident across all cohorts.
KW - Angiogenesis
KW - Angiopoietins
KW - Combination treatments
KW - Dose-limiting toxicities
KW - Targeted therapy
KW - Tie2 receptor
UR - http://www.scopus.com/inward/record.url?scp=84908022446&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84908022446&partnerID=8YFLogxK
U2 - 10.1016/j.ygyno.2014.07.003
DO - 10.1016/j.ygyno.2014.07.003
M3 - Article
VL - 135
SP - 25
EP - 33
JO - Gynecologic Oncology
JF - Gynecologic Oncology
SN - 0090-8258
IS - 1
ER -