Seagen Announces Results from Phase 2 Clinical Trial of ADCETRIS® (brentuximab vedotin) with Novel Immunotherapy Combination in Patients with Advanced- and Early-Stage Classical Hodgkin Lymphoma
Seagen Inc. announced encouraging results from its phase 2 trial (SGN35-027) evaluating ADCETRIS in combination with nivolumab, doxorubicin, and dacarbazine for treating classical Hodgkin lymphoma. The trial reported an 88% complete response (CR) rate in advanced-stage patients and a 92% CR rate in early-stage patients. Notably, 95% of advanced-stage patients remained progression-free at 12 months. The therapy displayed a favorable safety profile with minimal serious adverse events. These promising outcomes suggest potential as a frontline treatment.
- 88% complete response (CR) rate in advanced-stage classical Hodgkin lymphoma (cHL).
- 92% CR rate in early-stage cHL patients.
- 95% progression-free survival (PFS) at 12 months with a median follow-up of 17 months.
- Favorable safety profile with no treatment-related deaths and low grade peripheral sensory neuropathy.
- None.
– ADCETRIS in Combination with Nivolumab, Doxorubicin and Dacarbazine Delivers
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– Regimen Was Well-Tolerated in Both Cohorts with No Treatment-Related Deaths and Less Than Half of Patients in Either Group Developed Any Grade Peripheral Sensory Neuropathy –
Results demonstrated a complete response (CR) rate of
“We are encouraged that ADCETRIS in combination with the immunotherapy nivolumab and standard chemotherapy agents showed promising efficacy and safety as a first-line treatment in patients with early- and advanced-stage classical Hodgkin lymphoma,” said
Part B Phase 2 Study of Brentuximab Vedotin, Nivolumab, Doxorubicin, and Dacarbazine (AN+AD) for Advanced Stage Classic Hodgkin Lymphoma (Abstract #314)
Part B of SGN35-027 is evaluating the novel ADCETRIS combination in 57 patients with advanced-stage cHL (Stage II with bulky disease, Stage III or IV). Results showed:
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An
88% CR rate (95% Confidence Interval [CI]: 76.3, 94.9) and93% ORR (95% CI: 83.0, 98.1) at the end of treatment. -
The estimated 12-month progression-free survival (PFS) rate was
95% (median follow-up 17.2 months [95% CI: 15.5, 17.5]). -
The most frequently reported treatment-related treatment-emergent adverse events (TEAEs) occurring in more than
40% of patients were nausea at65% (37/57), fatigue at47% (27/57) and peripheral sensory neuropathy at44% (25/57). -
Peripheral sensory neuropathy was primarily low grade (
4% Grade ≥3), and no patients discontinued due to peripheral sensory neuropathy.
Part C Phase 2 Study of Brentuximab Vedotin, Nivolumab, Doxorubicin, and Dacarbazine (AN+AD) for Early-Stage Classic Hodgkin Lymphoma (Abstract #4230)
Part C of SGN35-027 is evaluating the novel ADCETRIS combination in 125 patients with early-stage (non-bulky Stage I or II) cHL. Of 125 patients in the study, 76 were included at the time of efficacy assessment. Results showed:
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A
92% CR rate (95% CI: 83.6, 97.0) and a95% ORR (95% CI: 87.1, 98.5) at end of treatment (N=76). - Follow up is ongoing and PFS results are not yet available.
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The most frequently reported treatment-related TEAEs occurring in more than
30% of patients were nausea at68% (85/125), peripheral sensory neuropathy at42% (53/125), and fatigue at38% (47/125). -
Peripheral sensory neuropathy was primarily low grade (
2% Grade ≥3), and no patients discontinued due to peripheral sensory neuropathy.
About the SGN35-027 Clinical Study
SGN35-027 is an ongoing open-label, multiple part, multicenter, phase 2 clinical trial evaluating two brentuximab vedotin treatment combinations in patients with advanced and early-stage cHL. The trial includes three parts (Parts A, B, and C). Part A includes a combination of brentuximab vedotin and doxorubicin, vinblastine and dacarbazine (A+AVD), while Parts B and C include brentuximab vedotin in combination with nivolumab, doxorubicin, and dacarbazine (AN+AD). The primary endpoint for Part A is the proportion of patients with treatment-emergent febrile neutropenia. The primary endpoint for Parts B and C is the proportion of participants with complete response at end of treatment according to the Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC). Incidence of adverse events is a secondary endpoint for Parts B and C.
About Hodgkin Lymphoma
According to the
About ADCETRIS
ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of cHL and expressed on the surface of several types of lymphomas. It is approved in seven indications in the
- Adult patients with previously untreated Stage III/IV cHL, in combination with doxorubicin, vinblastine, and dacarbazine.
- Pediatric patients 2 years and older with previously untreated high risk cHL, in combination with doxorubicin, vincristine, etoposide, prednisone and cyclophosphamide.
- Adult patients with cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation.
- Adult patients with cHL after failure of auto-HSCT or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates.
- Adult patients with previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone.
- Adult patients with sALCL after failure of at least one prior multi-agent chemotherapy regimen.
- Adult patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.
ADCETRIS® (brentuximab vedotin) for injection
BOXED WARNING
PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML): JC virus infection resulting in PML and death can occur in ADCETRIS-treated patients.
CONTRAINDICATION
Contraindicated with concomitant bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation).
WARNINGS AND PRECAUTIONS
Peripheral neuropathy (PN): ADCETRIS causes PN that is predominantly sensory. Cases of motor PN have also been reported. ADCETRIS-induced PN is cumulative. Monitor for symptoms such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain, or weakness. Patients experiencing new or worsening PN may require a delay, change in dose, or discontinuation of ADCETRIS.
Anaphylaxis and infusion reactions: Infusion-related reactions (IRR), including anaphylaxis, have occurred with ADCETRIS. Monitor patients during infusion. If an IRR occurs, interrupt the infusion and institute appropriate medical management. If anaphylaxis occurs, immediately and permanently discontinue the infusion and administer appropriate medical therapy. Premedicate patients with a prior IRR before subsequent infusions. Premedication may include acetaminophen, an antihistamine, and a corticosteroid.
Hematologic toxicities: Fatal and serious cases of febrile neutropenia have been reported with ADCETRIS. Prolonged (≥1 week) severe neutropenia and Grade 3 or 4 thrombocytopenia or anemia can occur with ADCETRIS.
Administer G-CSF primary prophylaxis beginning with Cycle 1 for adult patients who receive ADCETRIS in combination with chemotherapy for previously untreated Stage III/IV cHL or previously untreated PTCL, and pediatric patients who receive ADCETRIS in combination with chemotherapy for previously untreated high risk cHL.
Monitor complete blood counts prior to each ADCETRIS dose. Monitor more frequently for patients with Grade 3 or 4 neutropenia. Monitor patients for fever. If Grade 3 or 4 neutropenia develops, consider dose delays, reductions, discontinuation, or G-CSF prophylaxis with subsequent doses.
Serious infections and opportunistic infections: Infections such as pneumonia, bacteremia, and sepsis or septic shock (including fatal outcomes) have been reported in ADCETRIS-treated patients. Closely monitor patients during treatment for infections.
Tumor lysis syndrome: Patients with rapidly proliferating tumor and high tumor burden may be at increased risk. Monitor closely and take appropriate measures.
Increased toxicity in the presence of severe renal impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with severe renal impairment. Avoid use in patients with severe renal impairment.
Increased toxicity in the presence of moderate or severe hepatic impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with moderate or severe hepatic impairment. Avoid use in patients with moderate or severe hepatic impairment.
Hepatotoxicity: Fatal and serious cases have occurred in ADCETRIS-treated patients. Cases were consistent with hepatocellular injury, including elevations of transaminases and/or bilirubin, and occurred after the first ADCETRIS dose or rechallenge. Preexisting liver disease, elevated baseline liver enzymes, and concomitant medications may increase the risk. Monitor liver enzymes and bilirubin. Patients with new, worsening, or recurrent hepatotoxicity may require a delay, change in dose, or discontinuation of ADCETRIS.
PML: Fatal cases of JC virus infection resulting in PML have been reported in ADCETRIS-treated patients. First onset of symptoms occurred at various times from initiation of ADCETRIS, with some cases occurring within 3 months of initial exposure. In addition to ADCETRIS therapy, other possible contributory factors include prior therapies and underlying disease that may cause immunosuppression. Consider PML diagnosis in patients with new-onset signs and symptoms of central nervous system abnormalities. Hold ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed.
Pulmonary toxicity: Fatal and serious events of noninfectious pulmonary toxicity, including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome, have been reported. Monitor patients for signs and symptoms, including cough and dyspnea. In the event of new or worsening pulmonary symptoms, hold ADCETRIS dosing during evaluation and until symptomatic improvement.
Serious dermatologic reactions: Fatal and serious cases of
Gastrointestinal (GI) complications: Fatal and serious cases of acute pancreatitis have been reported. Other fatal and serious GI complications include perforation, hemorrhage, erosion, ulcer, intestinal obstruction, enterocolitis, neutropenic colitis, and ileus. Lymphoma with pre-existing GI involvement may increase the risk of perforation. In the event of new or worsening GI symptoms, including severe abdominal pain, perform a prompt diagnostic evaluation and treat appropriately.
Hyperglycemia: Serious cases, such as new-onset hyperglycemia, exacerbation of pre-existing diabetes mellitus, and ketoacidosis (including fatal outcomes) have been reported with ADCETRIS. Hyperglycemia occurred more frequently in patients with high body mass index or diabetes. Monitor serum glucose and if hyperglycemia develops, administer anti-hyperglycemic medications as clinically indicated.
Embryo-fetal toxicity: Based on the mechanism of action and animal studies, ADCETRIS can cause fetal harm. Advise females of reproductive potential of this potential risk, and to avoid pregnancy during ADCETRIS treatment and for 6 months after the last dose of ADCETRIS.
ADVERSE REACTIONS
The most common adverse reactions (≥
DRUG INTERACTIONS
Concomitant use of strong CYP3A4 inhibitors has the potential to affect the exposure to monomethyl auristatin E (MMAE). Closely monitor adverse reactions.
USE IN SPECIAL POPULATIONS
Lactation: Breastfeeding is not recommended during ADCETRIS treatment.
Females and Males of Reproductive Potential: Advise females to report pregnancy immediately and advise males with female sexual partners of reproductive potential to use effective contraception during ADCETRIS treatment and for 6 months after the last dose of ADCETRIS.
Please see full Prescribing information, including BOXED WARNING, for ADCETRIS here.
About
Forward-Looking Statements
Certain statements made in this press release are forward looking, such as those, among others, relating to the therapeutic potential of ADCETRIS alone or in combination, its possible safety, efficacy and therapeutic uses, the SGN35-027 clinical trial and the potential for further investigation in the referenced treatment settings. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include without limitation the risk of delays, setbacks or failures in product development activities, even after encouraging results in earlier-stage trials, for a variety of reasons, including without limitation the difficulty and uncertainty of pharmaceutical product development and the potential for adverse events or safety signals, failure of clinical results to support continued development or regulatory approvals, and adverse regulatory actions. More information about the risks and uncertainties faced by
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1 https://www.cancer.org/cancer/hodgkin-lymphoma.html
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