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

Our plain-English summary of A phase 2, open-label study of brentuximab vedotin in patients with CD30-expressing solid tumors, by J.P. Sharman, J.J. Wheler, L. Einhorn, et al (Investigational New Drugs, 2019).

The study

• Authors: J.P. Sharman, J.J. Wheler, L. Einhorn, A. Dowlati, G.I. Shapiro, J. Hilton, J.M. Burke, T. Siddiqi, N. Whiting, S.I. Jalal
• Journal: Investigational New Drugs
• Published: 2019;37(4):738-747
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This phase 2, open-label study tested brentuximab vedotin, a lymphoma drug, in patients whose solid tumors carried a protein called CD30. Of 2693 patients screened, 103 (3.8%) were CD30-positive. Of these, 63 were treated at 1.8 or 2.4 mg/kg every three weeks. Twenty-six had mesothelioma (21 pleural, 5 peritoneal). Of 59 assessable patients, 11% (95% CI 4.9 to 22.9) had an objective response, meaning a complete or partial response under standard criteria: 1 complete, 6 partial. At some point, 55% (95% CI 42.4 to 68.8) had stable disease or better. Among 23 assessable mesothelioma patients, 2 (8%, 95% CI 1.1 to 28.0) had partial responses, both with pleural mesothelioma at the higher dose. In these 23, 65% (95% CI 42.7 to 83.6) had stable disease or better. Among all 26 treated, median progression-free survival was 2.5 months (95% CI 1.2 to 4.0). The most common adverse events reported during the study were fatigue (57%), nausea (33%) and decreased appetite (32%). The authors concluded that safety matched the drug's known profile and that it had modest single-agent activity in CD30-positive solid tumors.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Phase 2, open-label, single-arm drug trial (NCT01461538), sponsored by Seattle Genetics, Inc.
• Who was studied: Patients with CD30-expressing solid tumors. Of 2693 patients with solid tumors screened, 103 (3.8%) were CD30-positive and 63 were treated. These included 26 with mesothelioma (21 malignant pleural mesothelioma, 5 peritoneal) and patients with testicular and other cancers. Median age was 64 years, and most patients (92%) had received prior systemic therapy. Sites were in the USA; the text does not give enrollment dates.
• Exposure: Treatment with brentuximab vedotin, an anti-CD30 antibody-drug conjugate, given intravenously at 1.8 mg/kg every three weeks. After a protocol amendment it was also given at 2.4 mg/kg every three weeks. The article does not discuss asbestos exposure.
• Main results:
  • Among all efficacy-evaluable patients with solid tumors (59), the objective response rate (complete or partial response) was 11% (95% CI 4.9, 22.9).
  • Seven patients with solid tumors had an objective response: 1 complete response (testicular cancer) and 6 partial responses.
  • The disease control rate (stable disease or better at any point in the study) in all solid tumor patients was 55% (95% CI 42.4, 68.8).
  • The median duration of objective response among all solid tumor patients was 2.92 months (95% CI 1.51 to 7.03 months).
  • Among 23 evaluable mesothelioma patients, the objective response rate was 8% (95% CI 1.1, 28.0). This was 2 partial responses, both in patients with malignant pleural mesothelioma treated at 2.4 mg/kg. No patient with peritoneal mesothelioma responded.
  • The disease control rate in the 23 evaluable mesothelioma patients was 65% (95% CI 42.7, 83.6).
  • Median progression-free survival was 2.1 months (95% CI 1.2 to 2.8) in all solid tumor patients.
  • Median progression-free survival in the 26 treated mesothelioma patients was 2.5 months (95% CI 1.2, 4.0).
  • The most common adverse events reported among all treated patients were fatigue (57%), nausea (33%) and decreased appetite (32%). The events investigators considered related to treatment were fatigue (38%), nausea (24%), alopecia (21%) and peripheral sensory neuropathy (21%).
  • Peripheral sensory neuropathy occurred in 26% of the 2.4 mg/kg group versus 15% of the 1.8 mg/kg group.
  • Six patients (10%) stopped treatment because of an adverse event.
• The authors' conclusion: The authors concluded that brentuximab vedotin's safety profile in solid tumors was similar to its known profile in lymphoma. They also concluded that it had modest single-agent activity in CD30-positive solid tumors, with a response rate they described as similar to already approved second-line treatments.

Topics

Medical terms in this study, explained in our Lexicon: Disease Progression, Mesothelioma.

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