|Seattle Genetics and Bristol-Myers Squibb Announce Initiation of Phase 1/2 Clinical Trial of ADCETRIS® (Brentuximab Vedotin) in Combination with Opdivo® (Nivolumab) in Relapsed or Refractory Non-Hodgkin Lymphoma|
-Second of Two Planned Trials Combining ADCETRIS and Opdivo Under Clinical Collaboration Agreement-
“This is the second corporate-sponsored clinical trial to evaluate
ADCETRIS combined with a checkpoint inhibitor to determine if the
combination can improve patient outcomes,” said
The phase 1/2 open-label, multi-center, clinical trial is designed to
evaluate the safety, tolerability and antitumor activity of ADCETRIS in
combination with Opdivo in patients with relapsed or refractory
“Bristol-Myers Squibb continues to strengthen its industry-leading
development program for Opdivo and its rapidly expanding
hematology portfolio,” said
In addition to the two ongoing Opdivo combination trials under
the collaboration with
ADCETRIS is not currently approved for frontline treatment or for the
About ADCETRIS® (Brentuximab Vedotin)
ADCETRIS is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics’ proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells. CD30 is a member of the tumor necrosis factor receptor (TNFR) superfamily. In HL, CD30 may be involved in tumor cell proliferation by interacting with immune cells in the tumor microenvironment.
ADCETRIS for intravenous injection has received approval from the
ADCETRIS was granted conditional marketing authorization by the
Lymphoma is a general term for a group of cancers that originate in the
lymphatic system. There are two major categories of lymphoma: HL and
Surgery, radiation, cytotoxic or targeted therapies have represented the mainstay of cancer treatment over the last several decades, but long-term survival and a positive quality of life have remained elusive for many patients with advanced disease.
To address this unmet medical need,
ADCETRIS (brentuximab vedotin) U.S. Important Safety Information
Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death can occur in patients receiving ADCETRIS® (brentuximab vedotin).
ADCETRIS is contraindicated with concomitant bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation).
Warnings and Precautions
Most Common Adverse Reactions:
ADCETRIS was studied as monotherapy in 160 patients with relapsed classical HL and sALCL in two uncontrolled single-arm trials. Across both trials, the most common adverse reactions (≥20%), regardless of causality, were neutropenia, peripheral sensory neuropathy, fatigue, nausea, anemia, upper respiratory tract infection, diarrhea, pyrexia, rash, thrombocytopenia, cough and vomiting.
ADCETRIS was studied in 329 patients with classical HL at high risk of relapse or progression post-auto-HSCT in a placebo-controlled randomized trial. The most common adverse reactions (≥20%) in the ADCETRIS-treatment arm (167 patients), regardless of causality, were neutropenia, peripheral sensory neuropathy, thrombocytopenia, anemia, upper respiratory tract infection, fatigue, peripheral motor neuropathy, nausea, cough, and diarrhea.
Concomitant use of strong CYP3A4 inhibitors or inducers, or P-gp inhibitors, has the potential to affect the exposure to monomethyl auristatin E (MMAE).
Use in Specific Populations:
MMAE exposure and adverse reactions are increased in patients with moderate or severe hepatic impairment or severe renal impairment. Avoid use.
For additional Important Safety Information, including Boxed WARNING, please see the full Prescribing Information for ADCETRIS at http://www.seattlegenetics.com/pdf/adcetris_USPI.pdf.
Indication and Important Safety Information for OPDIVO® (nivolumab)
OPDIVO® (nivolumab) is indicated for the treatment of
patients with metastatic non-small cell lung cancer (NSCLC) with
progression on or after platinum-based chemotherapy. Patients with EGFR
or ALK genomic tumor aberrations should have disease progression on
IMPORTANT SAFETY INFORMATION
Immune-mediated pneumonitis or interstitial lung disease, including fatal cases, occurred with OPDIVO treatment. Across the clinical trial experience with solid tumors, fatal immune-mediated pneumonitis occurred with OPDIVO. Monitor patients for signs with radiographic imaging and symptoms of pneumonitis. Administer corticosteroids for Grade 2 or greater pneumonitis. Permanently discontinue OPDIVO for Grade 3 or 4 and withhold until resolution for Grade 2. In Checkmate 057, immune-mediated pneumonitis, including interstitial lung disease, occurred in 3.4% (10/287) of patients receiving OPDIVO: Grade 3 (n=5), Grade 2 (n=2), and Grade 1 (n=3).
Immune-mediated colitis can occur with OPDIVO treatment. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 (of more than 5 days duration), 3, or 4 colitis. Withhold OPDIVO for Grade 2 or 3 and permanently discontinue for Grade 4 or recurrent colitis upon restarting OPDIVO. In Checkmate 057, diarrhea or colitis occurred in 17% (50/287) of patients receiving OPDIVO. Immune-mediated colitis occurred in 2.4% (7/287) of patients: Grade 3 (n=3), Grade 2 (n=2), and Grade 1 (n=2).
Immune-mediated hepatitis can occur with OPDIVO treatment. Monitor patients for abnormal liver tests prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater transaminase elevations. Withhold OPDIVO for Grade 2 and permanently discontinue for Grade 3 or 4 immune-mediated hepatitis. In Checkmate 057, one patient (0.3%) developed immune-mediated hepatitis.
Hypophysitis, adrenal insufficiency, thyroid disorders, and type 1 diabetes mellitus can occur with OPDIVO treatment. Monitor patients for signs and symptoms of hypophysitis, signs and symptoms of adrenal insufficiency during and after treatment, thyroid function prior to and periodically during treatment and hyperglycemia. Administer corticosteroids for Grade 2 or greater hypophysitis. Withhold OPDIVO for Grade 2 or 3 and permanently discontinue for Grade 4 hypophysitis. Administer corticosteroids for Grade 3 or 4 adrenal insufficiency. Withhold OPDIVO for Grade 2 and permanently discontinue for Grade 3 or 4 adrenal insufficiency. Administer hormone replacement therapy for hypothyroidism. Initiate medical management for control of hyperthyroidism. Administer insulin for type 1 diabetes. Withhold OPDIVO for Grade 3 and permanently discontinue for Grade 4 hyperglycemia. In Checkmate 037, 066, and 057, <1.0% of OPDIVO-treated patients developed adrenal insufficiency. In Checkmate 057, Grade 1 or 2 hypothyroidism, including thyroiditis, occurred in 7% (20/287) and elevated TSH occurred in 17% of patients receiving OPDIVO. Grade 1 or 2 hyperthyroidism occurred in 1.4% (4/287) of patients.
Immune-Mediated Nephritis and Renal Dysfunction
Immune-mediated nephritis can occur with OPDIVO treatment. Monitor patients for elevated serum creatinine prior to and periodically during treatment. For Grade 2 or 3 increased serum creatinine, withhold OPDIVO and administer corticosteroids; if worsening or no improvement occurs, permanently discontinue OPDIVO. Administer corticosteroids for Grade 4 serum creatinine elevation and permanently discontinue OPDIVO. In Checkmate 057, Grade 2 immune-mediated renal dysfunction occurred in 0.3% (1/287) of patients receiving OPDIVO.
Immune-mediated rash can occur with OPDIVO treatment. Severe rash (including rare cases of fatal toxic epidermal necrolysis) occurred in the clinical program of OPDIVO. Monitor patients for rash. Administer corticosteroids for Grade 3 or 4 rash. Withhold OPDIVO for Grade 3 and permanently discontinue for Grade 4. In Checkmate 057, immune-mediated rash occurred in 6% (17/287) of patients receiving OPDIVO, including four Grade 3 cases.
Immune-mediated encephalitis can occur with OPDIVO treatment. Withhold OPDIVO in patients with new-onset moderate to severe neurologic signs or symptoms and evaluate to rule out other causes. If other etiologies are ruled out, administer corticosteroids and permanently discontinue OPDIVO for immune-mediated encephalitis. Across clinical trials of 8490 patients receiving OPDIVO as a single agent or in combination with ipilimumab, <1.0% of patients were identified as having encephalitis. In Checkmate 057, fatal limbic encephalitis occurred in one patient (0.3%) receiving OPDIVO.
Other Immune-Mediated Adverse Reactions
Based on the severity of the adverse reaction, permanently discontinue or withhold treatment, administer high-dose corticosteroids, and, if appropriate, initiate hormone-replacement therapy. The following clinically significant immune-mediated adverse reactions occurred in <1.0% of OPDIVO-treated patients: uveitis, pancreatitis, facial and abducens nerve paresis, demyelination, polymyalgia rheumatica, autoimmune neuropathy, Guillain-Barre syndrome, hypopituitarism, and systemic inflammatory response syndrome. Across clinical trials of OPDIVO as a single agent administered at doses 3 mg/kg and 10 mg/kg, additional clinically significant, immune-mediated adverse reactions were identified: motor dysfunction, vasculitis, and myasthenic syndrome.
Severe infusion reactions have been reported in <1.0% of patients in clinical trials of OPDIVO as a single agent. Discontinue OPDIVO in patients with Grade 3 or 4 infusion reactions. Interrupt or slow the rate of infusion in patients with Grade 1 or 2. In Checkmate 057 and 066, Grade 2 infusion reactions occurred in 1.0% (5/493) of patients receiving OPDIVO.
Based on its mechanism of action, OPDIVO can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with an OPDIVO-containing regimen and for at least 5 months after the last dose of OPDIVO.
It is not known whether OPDIVO is present in human milk. Because many drugs, including antibodies, are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from OPDIVO-containing regimen, advise women to discontinue breastfeeding during treatment.
Serious Adverse Reactions
In Checkmate 057, serious adverse reactions occurred in 47% of patients receiving OPDIVO. The most frequent serious adverse reactions reported in ≥2% of patients were pneumonia, pulmonary embolism, dyspnea, pleural effusion, and respiratory failure.
Common Adverse Reactions
In Checkmate 057, the most common adverse reactions (≥20%) reported with OPDIVO were fatigue (49%), musculoskeletal pain (36%), cough (30%), decreased appetite (29%), and constipation (23%).
Please see U.S. Full Prescribing Information for OPDIVO.
Seattle Genetics Forward-Looking Statement
Certain of the statements made in this press release are
forward-looking, such as those, among others, relating to the future
potential therapeutic uses of ADCETRIS (including in combination with Opdivo)
and future clinical and regulatory progress. 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 risks related to adverse clinical results associated
with the use of ADCETRIS or Opdivo (or the combination), the
failure of the companies to continue their collaboration or execute on
the planned clinical trials or adverse regulatory action More
information about the risks and uncertainties faced by
Bristol-Myers Squibb Forward-Looking Statement
This press release contains “forward-looking statements” as that term
is defined in the Private Securities Litigation Reform Act of 1995
regarding the research, development and commercialization of
pharmaceutical products. Such forward-looking statements are based on
current expectations and involve inherent risks and uncertainties,
including factors that could delay, divert or change any of them, and
could cause actual outcomes and results to differ materially from
current expectations. No forward-looking statement can be guaranteed.
Among other risks, there can be no guarantee that Opdivo will receive
approval for any additional indications described herein or, if
approved, become commercially successful in such indications.
Forward-looking statements in this press release should be evaluated
together with the many uncertainties that affect