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

Ignace Vergote, Russell J. Schilder, Charles H. Pippitt, Shirley Wong, Alan N. Gordon, Sidney A Scudder, Frederic Kridelka, Luc Dirix, Joseph W. Leach, Sumitra Ananda, Nuwan Nanayakkara, Rebeca Melara, Michael B. Bass, Jason Litten, Henry Adewoye, Robert M. Wenham

Research output: Contribution to journalArticle

14 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)25-33
Number of pages9
JournalGynecologic Oncology
Volume135
Issue number1
DOIs
StatePublished - Oct 1 2014

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Topotecan
Platinum
Ovarian Neoplasms
Pulmonary Embolism
Disease Progression
Intestinal Perforation
Hypokalemia
Pleural Effusion
Sudden Death
Neutropenia
Chest Pain
Drug Interactions
Granulocytes
Dyspnea
Nausea
Lung Diseases
Disease-Free Survival
Fatigue
trebananib
liposomal doxorubicin

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 journalArticle

Vergote, I, Schilder, RJ, Pippitt, CH, Wong, S, Gordon, AN, Scudder, SA, Kridelka, F, Dirix, L, Leach, JW, Ananda, S, Nanayakkara, N, Melara, R, Bass, MB, Litten, J, Adewoye, H & Wenham, RM 2014, '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', Gynecologic Oncology, vol. 135, no. 1, pp. 25-33. https://doi.org/10.1016/j.ygyno.2014.07.003
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. / 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. In: Gynecologic Oncology. 2014 ; Vol. 135, No. 1. pp. 25-33.
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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.",
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author = "Ignace Vergote and Schilder, {Russell J.} and Pippitt, {Charles H.} and Shirley Wong and Gordon, {Alan N.} and Scudder, {Sidney A} and Frederic Kridelka and Luc Dirix and Leach, {Joseph W.} and Sumitra Ananda and Nuwan Nanayakkara and Rebeca Melara and Bass, {Michael B.} and Jason Litten and Henry Adewoye and Wenham, {Robert M.}",
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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

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