High-risk classic Hodgkin lymphoma (cHL) first-line treatment! US FDA approves CD30-targeted drug Adcetris: treatment of pediatric patients aged ≥ 2 years old!

Nov.
16, 2022 /Biovalley BIOON/ -- Seagen Gene (Seagen) today announced that the U.
S.
Food and Drug Administration (FDA) has approved CD30-targeted antibody drug conjugate (ADC) Adcetris (brentuximab vedotin, bentuximab for injection): plus standard of care dose intensive chemotherapy AVE-PC (doxorubicin, vincristine, etoposide, prednisone, cyclophosphamide) for the treatment of pediatric patients
2 years of age and older with previously untreated high-risk classical Hodgkin lymphoma (cHL).

Adcetris is an accepted standard of care
medication for the treatment of adult patients with classic Hodgkin lymphoma (cHL).
This approval will expand its scope to include: children and adolescents with high-risk cHL who have not previously been treated
.
cHL accounts for about 6% of all childhood cancers and is the most common cancer
in adolescents aged 15-19 years.
About one-third of people with Hodgkin lymphoma (HL) are classified as high-risk, usually stage
IIB, IIIB, IVA, or IVB.
cHL accounts for about 90%
of HL.
People with cHL have abnormal white blood cells, which usually have a special protein CD30 on their surface, which is a key marker of cHL
.

The approval is based on the results of the
Phase 3 AHOD1331 trial.
The trial, conducted by the Pediatric Oncology Collaboration (COG), enrolled 587 previously untreated children and young adults (2 to 21 years of age) with high-risk cHL who were randomized to receive Adcetris plus AVE-PC (BV-AVE-PC regimen), or the current pediatric dose augmentation regimen ABVE-PC (doxorubicin [Adriamycin], bleomycin], vincristine [ vincristine], etoposide [etoposide], prednisone, cyclophosphamide).

The results of the trial were presented
in June this year at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.
The data showed that BV-AVE-PC regimens achieved better event-free survival (EFS)
compared with current paediatric dose-intensive regimens ABVE-PC as part of multimodal therapy.

Patients in the BV-AVE-PC regimen had a 59% lower risk of disease progression or recurrence, second malignancy (SMN), or death compared with the ABVE-PC regimen, with clinically significant and statistically significant differences (hazard ratio [HR] = 0.
41; 95% CI: 0.
25 to 0.
67; p=0.
0002).

At a median follow-up of 42.
1 months, the 3-year event-free survival (EFS) rate was 92.
1% in the BV-AVE-PC regimen group compared with 82.
5%
in the ABVE-PC regimen group.

Treatment with Adcetris in combination with AVE-PC has a well-tolerated and manageable safety profile
in pediatric patients.
Grade 3 adverse events recorded, including febrile neutropenia, were comparable between groups and consistent
with known dose-intensive chemotherapy regimens.
The incidence of grade 2 peripheral neuropathy above grade 2 was similar
in the 2 groups.
No deaths
occurred during treatment.

Adcetris: Redefining the benchmark for first-line treatment of CD30-positive lymphoma

Lymphoma is an umbrella term for a group of cancers that originate in the lymphatic system and affect a type of white blood cell
that becomes a type of lymphocytes.
Lymphomas are mainly divided into 2 main categories: Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL).

HL differs from other types of lymphoma in the presence of a characteristic cell called a Reed-Sternberg cell, which usually has a special protein called CD30 on the surface of the cell that is a key marker of
HL.
About 95% of tumor cells in HL patients express CD30
.
According to the American Cancer Society (ACS), in 2022, there will be 8540 new cases of HL in the United States, and an estimated 920 people will die from the disease
.
Classical Hodgkin lymphoma (cHL) accounts for about 90%
of HL.
cHL has a bimodal age incidence that peaks in adolescents and young adults aged 15-30 years and then again in adults aged 55 years or older
.

Adcetris is an antibody conjugate drug (ADC), an ADC drug consisting of a monoclonal antibody targeting the CD30 protein and a microtubule disruptor (monomethylauristatin E, MMAE) conjugated by a protease-sensitive crosslinker technology that is proprietary to Seattle Genetics
.
CD30 protein is a clear marker of classical HL, while Auristatin E hinders cell division
by inhibiting the polymerization of tubulin.
Adcetris is stable in the blood, releasing MMAE after internalization by CD30-positive tumor cells
.

Adcetris, the standard of care for the treatment of relapsed or refractory (r/r) cHL, was developed by Seattle Genomics, and Takeda entered into a licensing agreement in 2009 to obtain commercialization rights for the drug in countries around the world except the United States and Canada
.
Up to now, Adcetris has been approved by more than 70 countries around the world for up to 6 indications, which vary
from country to country.

In the US, Adcetris has previously been approved for 6 adult indications, including: (1) combination of doxorubicin + vincristine + dacarbazine (AVD) for first-line treatment of stage III or IV classical Hodgkin lymphoma (cHL) that has not been previously treated (treatment-naïve); (2) cHL with elevated risk of recurrence or progression after receiving autologous hematopoietic stem cell transplantation (ASCT) consolidation; (3) cHL that has failed to receive autologous HSCT therapy, or is not suitable for autologous HSCT and has failed to receive at least 2 multi-agent chemotherapy regimens; (4) Combined with cyclophosphamide + doxorubicin + prednisone, first-line treatment of systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphoma (PTCL) that has not been treated (naïve), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise prescribed; (5) sALCL who have previously received at least one multi-agent chemotherapy regimen for treatment failure; (6) Primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF)
that have previously received systematic therapy.

In China, the National Medical Products Administration (NMPA) officially approved Adaptive (English trade name: Adcetris, generic name: brentuximab vedotin, vebutuximab for injection) in May 2020 for the treatment of adult patients
with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL) or CD30-positive Hodgkin lymphoma (HL).

Currently, Takeda and Seattle Genetics are actively pursuing a large Phase III clinical development program with the goal of making Adcetris a basic care drug for CD30-positive lymphoma and redefining the clinical first-line treatment
of lymphoma.
(Biovalley Bioon.
com)

Seagen Announces U.
S.
FDA Approval of New Indication for ADCETRIS? (brentuximab vedotin) for Children with Previously Untreated High Risk Hodgkin Lymphoma