A phase 2, open-label study of brentuximab vedotin in patients with CD30-expressing solid tumors

Jeffrey P. Sharman, Jennifer J. Wheler, Lawrence Einhorn, Afshin Dowlati, Geoffrey I. Shapiro, John Hilton, John M. Burke, Tanya Siddiqi, Nancy Whiting, Shadia Jalal

Research output: Contribution to journalArticle

Abstract

Purpose Brentuximab vedotin (BV) is an anti-CD30 antibody-drug conjugate used in the treatment of several types of lymphomas. Expression of the target antigen has also been reported on a variety of malignant tumors of nonlymphoid origin. This phase 2, open-label study evaluated the safety and antitumor activity of BV in patients with CD30-expressing nonlymphomatous malignancies. Methods Patients were dosed with 1.8 or 2.4 mg/kg BV once every three weeks. Antitumor activity was assessed at Cycles 2, 4, and every 4 cycles thereafter. Patients with stable disease or better were eligible to continue treatment until disease progression, unacceptable toxicity, or study closure. Results Of the 2693 patients screened, 3.8% had solid tumors with CD30 expression and 63 eligible patients with solid tumors enrolled in this study. The most common CD30 positive solid tumors were testicular cancer and mesothelioma. Both subtypes had more than one patient with an objective response. The median duration of BV exposure was 6.1 weeks. The disease control rate, defined as achieving stable disease or better at any point during the study, was 55%. The objective response rate was 11%, with a median duration of response of 2.92 months. The most common adverse events reported were fatigue (57%), nausea (33%), and decreased appetite (32%). Conclusion The safety profile of BV in patients with solid tumors was similar to the known safety profile of BV. In solid tumors, BV had modest activity as a single agent, which was similar to other second-line treatments already available to patients.

Original languageEnglish (US)
JournalInvestigational New Drugs
DOIs
StatePublished - Jan 1 2019

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Neoplasms
Safety
cAC10-vcMMAE
Mesothelioma
Testicular Neoplasms
Appetite
Nausea
Fatigue
Disease Progression
Anti-Idiotypic Antibodies
Lymphoma
Therapeutics
Antigens
Pharmaceutical Preparations

Keywords

  • Antibody-drug conjugate
  • Brentuximab vedotin
  • CD-30
  • Solid tumors

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

Cite this

A phase 2, open-label study of brentuximab vedotin in patients with CD30-expressing solid tumors. / Sharman, Jeffrey P.; Wheler, Jennifer J.; Einhorn, Lawrence; Dowlati, Afshin; Shapiro, Geoffrey I.; Hilton, John; Burke, John M.; Siddiqi, Tanya; Whiting, Nancy; Jalal, Shadia.

In: Investigational New Drugs, 01.01.2019.

Research output: Contribution to journalArticle

Sharman, Jeffrey P. ; Wheler, Jennifer J. ; Einhorn, Lawrence ; Dowlati, Afshin ; Shapiro, Geoffrey I. ; Hilton, John ; Burke, John M. ; Siddiqi, Tanya ; Whiting, Nancy ; Jalal, Shadia. / A phase 2, open-label study of brentuximab vedotin in patients with CD30-expressing solid tumors. In: Investigational New Drugs. 2019.
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abstract = "Purpose Brentuximab vedotin (BV) is an anti-CD30 antibody-drug conjugate used in the treatment of several types of lymphomas. Expression of the target antigen has also been reported on a variety of malignant tumors of nonlymphoid origin. This phase 2, open-label study evaluated the safety and antitumor activity of BV in patients with CD30-expressing nonlymphomatous malignancies. Methods Patients were dosed with 1.8 or 2.4 mg/kg BV once every three weeks. Antitumor activity was assessed at Cycles 2, 4, and every 4 cycles thereafter. Patients with stable disease or better were eligible to continue treatment until disease progression, unacceptable toxicity, or study closure. Results Of the 2693 patients screened, 3.8{\%} had solid tumors with CD30 expression and 63 eligible patients with solid tumors enrolled in this study. The most common CD30 positive solid tumors were testicular cancer and mesothelioma. Both subtypes had more than one patient with an objective response. The median duration of BV exposure was 6.1 weeks. The disease control rate, defined as achieving stable disease or better at any point during the study, was 55{\%}. The objective response rate was 11{\%}, with a median duration of response of 2.92 months. The most common adverse events reported were fatigue (57{\%}), nausea (33{\%}), and decreased appetite (32{\%}). Conclusion The safety profile of BV in patients with solid tumors was similar to the known safety profile of BV. In solid tumors, BV had modest activity as a single agent, which was similar to other second-line treatments already available to patients.",
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