Phase II Trial of Brentuximab Vedotin in Relapsed/Refractory Germ Cell Tumors
Open accessAbstract
Background CD-30 is highly expressed in some patients with non-seminomatous germ-cell tumors. Brentuximab vedotin is an antibody-drug conjugate directed to CD-30. We report a phase 2 trial of brentuximab vedotin in patients with chemo-refractory GCT. Patients and methods This is a single arm, two cohort phase 2 trial investigating brentuximab vedotin 1.8 mg/kg IV every 3 weeks until disease progression or intolerable toxicities in patients with relapsed GCT who have no curative options. Patients with mGCT who progressed after first line cisplatin-based chemotherapy and after at least 1 salvage regimen (high-dose or standard-dose chemotherapy) were eligible. CD30 expression was assessed and two cohorts defined: CD30 positive and CD30 negative/unknown. Results 18 patients were enrolled. Median age 34.7 (range, 23-56). All patients had non-seminoma. Median AFP 4.9 (range, 1-219,345) and hCG 282 (range, 0.6-172,064). Five patients had late relapse (> 2 years). Median number of previous chemotherapy regimens was 3 (range, 2-7). Ten patients received prior high-dose chemotherapy. Seven patients had positive CD30 staining. There were two grade 3 treatment-related adverse events. No partial or complete responses were observed. 6 patients achieved radiographic stable disease (range, 9-14.9 weeks), 5 had elevated AFP or hCG at trial entry and all 5 had transient > 50% decline in baseline AFP/hCG: 4 had CD30 -ve and 2 had CD30 + ve staining; 10 patients had progression of disease as their best response; 2 were not evaluable for response. Conclusion Brentuximab vedotin does not appear to have clinically meaningful single-agent activity in patients with refractory GCT.
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Median OS was 5 months in the CD30-negative group.
“Median overall survival (OS) was 2.5 and 5 months in the CD30-positive and CD30-negative groups, respectively [56].”
From The Immune Landscape and Immunotherapeutic Strategies in Platinum-Refractory Testicular Germ Cell Tumors (2024) · cites this paper as [56]
The Efficacy section reports median OS of 5.9 months in the CD30-negative cohort, not 5 months. The citing sentence's 2.5-month figure for the CD30-positive cohort matches the paper, but the claim about the CD30-negative cohort does not. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredFour of six stable disease patients were CD30 negative.
“while the remaining four were in the CD30 negative group.”
From The Immune Landscape and Immunotherapeutic Strategies in Platinum-Refractory Testicular Germ Cell Tumors (2024) · cites this paper as [56]
Out of the 12 remaining patients, 10 experienced progressive disease as their best response.
“Out of the 12 remaining patients, 10 experienced progressive disease as their best response.”
From The Immune Landscape and Immunotherapeutic Strategies in Platinum-Refractory Testicular Germ Cell Tumors (2024) · cites this paper as [56]
Out of 18 patients, six had stable disease.
“Out of the 18 patients who participated in the study, six of them had stable disease.”
From The Immune Landscape and Immunotherapeutic Strategies in Platinum-Refractory Testicular Germ Cell Tumors (2024) · cites this paper as [56]
In a phase II one arm study of 18 patients, brentuximab vedotin was investigated in CD30-positive and CD30-negative/unknown patients, and no partial or complete responses were observed.
“No partial or complete responses were observed.”
From The Immune Landscape and Immunotherapeutic Strategies in Platinum-Refractory Testicular Germ Cell Tumors (2024) · cites this paper as [56]
Two of six stable disease patients were CD30 positive.
“Two of the six patients belonged to the CD30 positive group”
From The Immune Landscape and Immunotherapeutic Strategies in Platinum-Refractory Testicular Germ Cell Tumors (2024) · cites this paper as [56]
Median PFS in the CD30-negative group was 1.4 months.
“and 1.4 months in the CD30-negative group.”
From The Immune Landscape and Immunotherapeutic Strategies in Platinum-Refractory Testicular Germ Cell Tumors (2024) · cites this paper as [56]
All five patients had an initial decline of more than 50% in AFP or hCG levels that started to rise again at the time of disease progression.
“However, all five patients had an initial decline of more than 50% in AFP or hCG levels that started to rise again at the time of disease progression.”
From The Immune Landscape and Immunotherapeutic Strategies in Platinum-Refractory Testicular Germ Cell Tumors (2024) · cites this paper as [56]
Among the six patients with stable disease, five had elevated levels of AFP or hCG at the beginning of the trial.
“Among the six patients with stable disease, five had elevated levels of AFP or hCG at the beginning of the trial.”
From The Immune Landscape and Immunotherapeutic Strategies in Platinum-Refractory Testicular Germ Cell Tumors (2024) · cites this paper as [56]
Two patients, one from CD30 positive group and one from CD30 negative group, died before the first disease re-evaluation.
“Two patients, one from the CD30 positive group and one from the CD30 negative group died before the first disease re-evaluation.”
From The Immune Landscape and Immunotherapeutic Strategies in Platinum-Refractory Testicular Germ Cell Tumors (2024) · cites this paper as [56]
Median PFS in the CD30-positive group was 1.2 months.
“Median progression-free survival (PFS) in the CD30-positive group was 1.2 months”
From The Immune Landscape and Immunotherapeutic Strategies in Platinum-Refractory Testicular Germ Cell Tumors (2024) · cites this paper as [56]
Median OS was 2.5 months in the CD30-positive group.
“Median overall survival (OS) was 2.5 and 5 months in the CD30-positive and CD30-negative groups, respectively [56].”
From The Immune Landscape and Immunotherapeutic Strategies in Platinum-Refractory Testicular Germ Cell Tumors (2024) · cites this paper as [56]
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Evmorfopoulos, K., Marsitopoulos, K., Karachalios, R., Karathanasis, A., Dimitropoulos, K., Tzortzis, V., Zachos, I., & Vlachostergios, P. J. (2024) · Cancers · doi:10.3390/cancers16020428 · Cited by 11 · see citing works
“Recently, a phase II one arm study enrolling 18 patients investigated brentuximab vedotin in CD30-positive and CD30-negative/unknown patients [56].”
BackgroundInfluential
- Authors
- Ashkar, R., Feldman, D. R., Adra, N., Zaid, M. A., Funt, S. A., Althouse, S. K., Perkins, S. M., Snow, C. I., Lazzara, K. M., Sego, L. M., Quinn, D. I., Hanna, N. H., Einhorn, L. H., & Albany, C.
- Affiliations
- Indiana University Health (US)
- Memorial Sloan Kettering Cancer Center (US)
- Indiana University Indianapolis (US)
- USC Norris Comprehensive Cancer Center (US)
- Corresponding author
- Adra, Nabil
- ORCID
- Venue
- Investigational New Drugs
- Published
- 2021-05-24
- Volume
- 39
- Issue
- 6
- Pages
- 1656-1663
- ISSN
- 0167-6997 (ISSN-L)
- 1573-0646
- PMC
- PMC9534326
- OpenAlex
- W3163953040
- Cited by
- 16
- References
- 28
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 3 · 2023: 3 · 2021: 1
- FWCI
- 1.64
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Investigational New Drugs (publishedVersion)
- Research Square (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Funders
- Seattle Genetics
- Topics
- Health Sciences › Medicine › Surgery › Testicular diseases and treatments
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
- Keywords
- brentuximab vedotin, CD30, non-seminoma, antibody-drug conjugates, CD30 expression, alpha-fetoprotein, human chorionic gonadotropin, salvage chemotherapy, treatment-related adverse events
- MeSH terms
- Antineoplastic Agents, Immunological, Brentuximab Vedotin, Adult, Female, Humans, Male, Middle Aged, Neoplasms, Germ Cell and Embryonal, Testicular Neoplasms, Ki-1 Antigen
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