Adcetris (brentuximab vedotin)

P2, N=155, Active, not recruiting, City of Hope Medical Center | Trial completion date: Mar 2024 --> Sep 2024 | Trial primary completion date: Mar 2024 --> Sep 2024

The combination of BV and ibrutinib was active in r/r HL; however, given significant toxicity, it cannot be recommended for future development.

P2, N=60, Not yet recruiting, Chinese PLA General Hospital

P2, N=137, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Trial completion date: Sep 2024 --> Mar 2024

P2, N=39, Active, not recruiting, City of Hope Medical Center | Trial completion date: Mar 2024 --> Dec 2024

Brentuximab vedotin and the PD-1 inhibitors have improved outcomes for classic Hodgkin lymphoma (cHL), but better therapies are needed for patients who relapse after these agents...Rational combinations with existing agents and next generation antibody and CAR-T constructs may improve response rates and durability. Identifying biomarkers of response to these immunotherapies and using more sensitive tools to assess response, such as circulating tumor DNA, may further inform treatment decisions and enable a precision medicine approach in the future.

P2, N=14, Completed, Imagine Institute | Active, not recruiting --> Completed | N=25 --> 14 | Trial completion date: Feb 2024 --> Sep 2023

P2, N=71, Recruiting, Memorial Sloan Kettering Cancer Center

P3, N=995, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2032 --> Apr 2025 | Trial primary completion date: Jun 2023 --> Mar 2024

P1/2, N=34, Completed, The Thai Lymphoma Study Group | Active, not recruiting --> Completed | Trial completion date: Dec 2023 --> Apr 2024 | Trial primary completion date: Dec 2023 --> Apr 2024

P2, N=72, Active, not recruiting, Bristol-Myers Squibb | Trial primary completion date: Jan 2024 --> Jun 2024

Brentuximab vedotin led to partial response and high-dose chemotherapy combined with autologous HSCT was performed...After cessation of alectinib, allogeneic bone marrow transplantation from an HLA 1-locus mismatched unrelated donor was performed after conditioning with fludarabine, busulfan, and total body irradiation. GVHD prophylaxis consisted of tacrolimus and short-term methotrexate...The lymphoma has not recurred for 2 years after allo-HSCT without resuming alectinib. The clinical course of our case suggests that alectinib bridging therapy and allo-HSCT are effective in relapsed/refractory ALK-positive ALCL.

Brentuximab vedotin-induced neuropathy is an overlooked complication. Based on four easily identifiable "red flags", we provide an algorithm to help non-neurologist physicians that care for BV-treated patients to detect BV-IN. The aim of the algorithm is to decrease the diagnostic and management delay of this disabling neuropathy.

P2, N=46, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Sep 2025 --> Mar 2024 | Trial primary completion date: Sep 2025 --> Mar 2024

P2, N=55, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Apr 2024 --> Apr 2025 | Trial primary completion date: Apr 2024 --> Apr 2025

This patient was diagnosed with angioimmunoblastic T-cell lymphoma 5 years ago and underwent multiple lines of anti-tumor therapy, including cytotoxic chemotherapy; epigenetic modifying drugs such as chidamide and azacitidine; the immunomodulator lenalidomide; and targeted therapy such as rituximab, a CD20-targeting antibody, and brentuximab vedotin, which targets CD30...Anti-tumor therapy was suspended and ganciclovir was used. The serum viral load decreased and organ functions were stabilized. The purpose of this report was to raise clinicians' awareness of opportunistic virus reactivation during anti-tumor treatment.

P=N/A, N=0, Withdrawn, Takeda | N=200 --> 0 | Not yet recruiting --> Withdrawn

P=N/A, N=50, Recruiting, Takeda | Not yet recruiting --> Recruiting

P1/2, N=41, Active, not recruiting, Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea | Trial completion date: Oct 2023 --> Oct 2024

P2, N=150, Recruiting, Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea | Phase classification: P2b --> P2

P2, N=11, Recruiting, Lawson Health Research Institute | Not yet recruiting --> Recruiting | Trial completion date: Mar 2026 --> Jul 2026 | Trial primary completion date: Nov 2025 --> Feb 2026

P2, N=84, Recruiting, Canadian Cancer Trials Group | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Jun 2024 --> Jun 2025

P1, N=29, Completed, City of Hope Medical Center | Active, not recruiting --> Completed

P2, N=48, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Dec 2024

P2, N=28, Recruiting, Deepa Jagadeesh | Trial completion date: Dec 2023 --> Jun 2027 | Trial primary completion date: Dec 2023 --> Jun 2024

Recently, we have compared the in vivo efficacy of CCR4-IL2-IT versus Brentuximab (FDA approved leading drug in CTCL market) in the same immunodeficient mouse CTCL model...The depletion of CCR4+ cell and CD25+ cell (two target cell populations of CCR4-IL2-IT) was observed in minipigs. The excellent safety profile promoted us to further develop CCR4-IL2-IT towards clinical trials.

P2, N=39, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Mar 2024

P2, N=155, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Mar 2024 | Trial primary completion date: Dec 2023 --> Mar 2024

In conclusion, 44% of ALCL patients, regardless of histological subtypes, showed a loss of/decrease in CD30 expression after receiving BV-containing therapy, but this phenomenon was not observed in CHL patients. A higher cumulative dose of BV and a lower amount of CD30 antigen in tumor cells in the initial biopsy materials might be predictors of a loss of/decrease in CD30 expression in ALCL patients.

The Glycine-Proline FAP-cleavable technology was directly benchmarked against linkers found in Adcetris™, Enhertu™, and Trodelvy™ structures by means of in vivo therapeutic experiments in mice bearing tumors with cellular or stromal FAP expression. OncoFAP-GlyPro-Exatecan and OncoFAP-GlyPro-MMAE emerged as the most efficacious anti-cancer therapeutics against FAP-positive cellular models. OncoFAP-GlyPro-MMAE exhibited a potent antitumor activity also against stromal models, and was therefore selected for clinical development.

Recent years have seen the introduction of novel agents into clinical practice; most of these target CD30, such as anti-CD30 monoclonal antibodies and conjugated antibodies (brentuximab vedotin), bispecific antibodies and cellular therapies, particularly anti-CD30 CAR-T cells. This paper briefly reviews the biology of CD30 that makes it a good therapeutic target and describes the anti-CD30 therapies that have emerged to date.

These entities are currently treated similarly with CHOP or CHOEP for CD30-negative diseases or brentuximab vedotin plus CHP for CD30-positive diseases, followed by consolidation with autologous stem cell transplant in first remission...Although current treatment strategies lump most disease entities together, future treatment will include distinct strategies for each disease subtype that optimizes therapy for individuals. This movement towards individualized therapy will ultimately lead to dramatic improvements in prognosis for patients with PTCL.

This includes the CD30 directed antibody drug conjugate brentuximab vedotin...The use of checkpoint inhibitors in the treatment of PTCL is still controversial, with best results seen in cases of extranodal natural killer cell/T-cell lymphoma. Bispecific antibody-based treatments and chimeric antigen receptor cell-based therapies are in clinical trials.

P1/2, N=59, Active, not recruiting, Takeda | Completed --> Active, not recruiting | Trial completion date: Sep 2021 --> Sep 2029

P2, N=23, Recruiting, Joseph Tuscano | Trial completion date: May 2024 --> May 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

P2, N=82, Active, not recruiting, Seagen Inc. | Recruiting --> Active, not recruiting

P1, N=132, Terminated, Seagen Inc. | Trial completion date: Apr 2025 --> Dec 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Jan 2025 --> Dec 2023; Study closed due to portfolio prioritization

P=N/A, N=95, Completed, Takeda | Active, not recruiting --> Completed

Additionally, CRISPR BNIP3 knockout caused proliferation defects and increased sensitivity to apoptosis. All the findings reveal a strong relationship between mitophagy and adverse prognosis of EBV DLBCL and discover a new regulatory mechanism of BNIP3-mediated mitophagy, which may help develop effective treatment regimens with anti-CD30 antibody brentuximab vedotin to improve the prognosis of CD30 EBV DLBCL patients.

P=N/A, N=100, Recruiting, Grupo Argentino de Tratamiento de la Leucemia Aguda | Trial primary completion date: Apr 2023 --> Mar 2024

Brentuximab vedotin (BV), as an antibody-drug conjugate (ADC) targeting CD30, is one of the first new drugs to significantly improve survival in patients with CD30+lymphomas...Therefore, this review highlights the CD30-mediated tumor-promoting mechanisms and the molecular factors that regulate CD30 expression. We hope that a better understanding of CD30 biology will provide new insights into clinical treatment and improve the survival and quality of life of lymphoma patients.

P3, N=20, Not yet recruiting, University Medical Center Groningen