First presentation of Phase 2 CheckMate -205 cohort C data in classical Hodgkin lymphoma patients following treatment with autologous hematopoietic stem cell transplantation and brentuximab vedotin
After a median follow-up of 8.8 months, Opdivo demonstrated an objective response rate as assessed by an independent radiologic review committee of 73% overall and median progression-free survival of 11.2 months
The safety profile of Opdivo was consistent with previously reported data in this tumor type, and no new clinically meaningful safety signals were identified
PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) today announced new results from CheckMate -205, a multi-cohort, single-arm, Phase 2 trial evaluating Opdivo (nivolumab) in patients with classical Hodgkin lymphoma (cHL). These results from cohort C (n=100) of the trial included patients with cHL who had received brentuximab vedotin before and/or after autologous hematopoietic stem cell transplantation (auto-HSCT). After a median follow-up of 8.8 months, the primary endpoint of objective response rate (ORR) per an independent radiologic review committee (IRRC) was 73% (n=73; 95% CI: 63.2-81.4) overall, which was consistent across patient subgroups regardless of the timing of prior brentuximab vedotin relative to auto-HSCT. The ORR was 70% (n=23; 95% CI: 51.3-84.4) in patients who received brentuximab vedotin only before auto-HSCT; 72% (n=41; 95% CI: 58.5-83.0) in patients who received brentuximab vedotin only after auto-HSCT; and 88% (n=7; 95% CI: 47.3-99.7) in patients who received brentuximab vedotin before and after auto-HSCT. The safety profile of Opdivo was consistent with previously reported data in this tumor type, and no new clinically meaningful safety signals were identified.
“These data from cohort C build on existing evidence supporting the benefit of Opdivo in classical Hodgkin lymphoma patients who have relapsed or progressed after autologous hematopoietic stem cell transplantation and post-transplantation brentuximab vedotin”
These data will be presented at the 10th International Symposium on Hodgkin Lymphoma (ISHL) in Cologne, Germany on Tuesday, October 25 at 3:00 p.m. CEST (Abstract #0149). This abstract was awarded the Karl Musshoff Prize for the Best Clinical Research Abstract, which is granted every three years in conjunction with ISHL for outstanding results in the field of Hodgkin lymphoma.
“These data from cohort C build on existing evidence supporting the benefit of Opdivo in classical Hodgkin lymphoma patients who have relapsed or progressed after autologous hematopoietic stem cell transplantation and post-transplantation brentuximab vedotin,” said Andreas Engert, M.D., study investigator and professor of Internal Medicine, Hematology and Oncology, University Hospital of Cologne, Cologne, Germany. “Results from cohort C indicated a benefit with Opdivo regardless of the order of prior treatment with autologous hematopoietic stem cell transplantation and brentuximab vedotin, providing important insights as we continue researching the potential role Opdivo could provide for heavily pre-treated classical Hodgkin lymphoma patients.”
In May 2016, the U.S. Food and Drug Administration approved Opdivo for the treatment of patients with cHL who have relapsed or progressed after auto-HSCT and post-transplantation brentuximab vedotin based on a combined analysis of data from cohort B of CheckMate -205 and the Phase 1 CheckMate -039 trial. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
In October 2016, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency recommended the approval of Opdivo for the treatment of adult patients with relapsed or refractory cHL after auto-HSCT and treatment with brentuximab vedotin based on data from cohort B of CheckMate -205 and CheckMate -039. The CHMP recommendation is now being reviewed by the European Commission, which has the authority to approve medicines for the European Union. Opdivo also is currently under regulatory review for cHL in Japan.
Fouad Namouni, M.D., head of development, Oncology, Bristol-Myers Squibb, commented, “We continue to expand our Immuno-Oncology science in hematology, and these latest results from CheckMate -205 will help inform our research into classical Hodgkin lymphoma and aid us in determining whether Opdivo may provide benefit to a broader population of patients living with this difficult-to-treat disease.”
About CheckMate -205 Cohort C
Key efficacy results from cohort C of CheckMate -205 are summarized below.
| Cohort C
| BV Only Before | BV Only After | BV Before and | ||||
| ORR per IRRC, n (%) [95% CI] | 73 (73) [63.2, 81.4] | 23 (70) [51.3, 84.4] | 41 (72) [58.5, 83.0] | 7 (88) [47.3, 99.7] | |||
| Complete response, n (%) [95% CI] | 17 (17.0) [10.2, 25.8] | 6 (18.2) [7.0, 35.5] | 7 (12.3) [5.1, 23.7] | 3 (38) [8.5, 75.5] | |||
| Partial response, n (%) [95% CI] | 56 (56.0) [45.7, 65.9] | 17 (51.5) [33.5, 69.2] | 34 (59.6) [45.8, 72.4] | 4 (50.0) [15.7, 84.3] | |||
| 6-month PFS rate per IRRC, % [95% CI] | 76.6 [66.3, 84.2] | 83.7 [65.1, 92.9] | 71.2 [56.7, 81.6] | 83.3 [27.3, 97.5] | |||
| Median PFS, months [95% CI] | 11.2 [8.5, NA] | 11.2 [8.5, NA] | 8.9 [8.3, NA] | NA [5.6, NA] | |||
| Median DOR, months [95% CI] | 7.0 [6.7, NA] | 7.0 [6.7, NA] | NA [5.4, NA] | NA [3.3, NA] | |||
| 6-month OS, % [95% CI] | 93.9 [86.9, 97.2] | 97 [80, 100] | 91 [80, 96] | 100 [100, 100] | |||
In CheckMate -205 cohort C, the safety profile of Opdivo was consistent with previously reported data in this tumor type, and no new clinically meaningful safety signals were identified. Treatment-related adverse events (AE) occurred in 68% of patients between the first dose and 30 days after the last dose of Opdivo. The most common treatment-related AEs were diarrhea, infusion-related reaction and fatigue (11% each). Grade 3/4 AEs occurred in 19% of patients. Serious treatment-related AEs were reported in 17% of patients, and treatment-related AEs leading to discontinuation occurred in 6% of patients. At present, no treatment-related deaths have been reported.
About CheckMate -205
CheckMate -205 is a Phase 2, open-label, international, multicenter, non-comparative, multi-cohort study that evaluated the safety and efficacy of Opdivo in adult patients with classical Hodgkin lymphoma (cHL). Cohort A included cHL patients who had received autologous hematopoietic stem cell transplantation (auto-HSCT) and who were brentuximab vedotin-naïve (n=63); cohort B included cHL patients who had received auto-HSCT followed by brentuximab vedotin (n=80); and cohort C included cHL patients who had received brentuximab vedotin before and/or after auto-HSCT (n=100). CheckMate -205 also includes cohort D, which is currently enrolling and evaluating Opdivo in combination with chemotherapy in newly diagnosed, advanced-stage cHL patients who are treatment-naïve (n=50).
Patients enrolled in this trial were treated with Opdivo 3 mg/kg intravenously every two weeks until disease progression or unacceptable toxicity; in cohort C, patients also were treated until investigator-assessed complete response (CR) lasting one year.
The primary endpoint of the study was objective response rate by independent radiologic review committee (IRRC) assessment. Secondary and other exploratory endpoints included duration of response (DOR) by IRRC assessment for CR rate and partial response rate, progression-free survival (PFS) by IRRC assessment, overall survival (OS) and safety.
About Classical Hodgkin Lymphoma
Hodgkin lymphoma (HL), also known as Hodgkin disease, is a cancer that starts in white blood cells called lymphocytes, which are part of the body’s immune system. Worldwide, there are about 66,000 new HL cases and 25,500 deaths from HL estimated each year. The disease is most often diagnosed in early adulthood (ages 20-40) and late adulthood (older than 55 years of age). Classical Hodgkin lymphoma is the most common type of HL, accounting for 95% of cases. There remains a significant unmet need for patients who relapse or who become refractory to approved treatments that are currently available.
Bristol-Myers Squibb & Immuno-Oncology: Advancing Oncology Research
At Bristol-Myers Squibb, patients are at the center of everything we do. Our vision for the future of cancer care is focused on researching and developing transformational Immuno-Oncology (I-O) medicines that will raise survival expectations in hard-to-treat cancers and will change the way patients live with cancer.
We are leading the scientific understanding of I-O through our extensive portfolio of investigational and approved agents, including the first combination of two I-O agents in metastatic melanoma, and our differentiated clinical development program, which is studying broad patient populations across more than 20 types of cancers with 11 clinical-stage molecules designed to target different immune system pathways. Our deep expertise and innovative clinical trial designs uniquely position us to advance the science of combinations across multiple tumors and potentially deliver the next wave of I-O combination regimens with a sense of urgency. We also continue to pioneer research that will help facilitate a deeper understanding of the role of immune biomarkers and inform which patients will benefit most from I-O therapies.
We understand making the promise of I-O a reality for the many patients who may benefit from these therapies requires not only innovation on our part but also close collaboration with leading experts in the field. Our partnerships with academia, government, advocacy and biotech companies support our collective goal of providing new treatment options to advance the standards of clinical practice.
About Opdivo
Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.
Opdivo’s leading global development program is based on Bristol-Myers Squibb’s scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has enrolled more than 25,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.
In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 57 countries, including the United States, the European Union and Japan. In October 2015, the company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 47 countries, including the United States and the European Union.
INDICATIONS
OPDIVO® (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 mutation-positive unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
OPDIVO® (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 wild-type unresectable or metastatic melanoma.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of patients with unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
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 FDA-approved therapy for these aberrations prior to receiving OPDIVO.
OPDIVO® (nivolumab) is indicated for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.
OPDIVO® (nivolumab) is indicated for the treatment of patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
IMPORTANT SAFETY INFORMATION
WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS
YERVOY can result in severe and fatal immune-mediated adverse reactions. These immune-mediated reactions may involve any organ system; however, the most common severe immune-mediated adverse reactions are enterocolitis, hepatitis, dermatitis (including toxic epidermal necrolysis), neuropathy, and endocrinopathy. The majority of these immune-mediated reactions initially manifested during treatment; however, a minority occurred weeks to months after discontinuation of YERVOY.
Assess patients for signs and symptoms of enterocolitis, dermatitis, neuropathy, and endocrinopathy and evaluate clinical chemistries including liver function tests (LFTs), adrenocorticotropic hormone (ACTH) level, and thyroid function tests at baseline and before each dose.
Permanently discontinue YERVOY and initiate systemic high-dose corticosteroid therapy for severe immune-mediated reactions.
Immune-Mediated Pneumonitis
OPDIVO can cause immune-mediated pneumonitis. Fatal cases have been reported. Monitor patients for signs with radiographic imaging and for symptoms of pneumonitis. Administer corticosteroids for Grade 2 or more severe pneumonitis. Permanently discontinue for Grade 3 or 4 and withhold until resolution for Grade 2. In patients receiving OPDIVO monotherapy, fatal cases of immune-mediated pneumonitis have occurred. Immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated pneumonitis occurred in 6% (25/407) of patients.
In Checkmate 205 and 039, pneumonitis, including interstitial lung disease, occurred in 4.9% (13/263) of patients receiving OPDIVO. Immune-mediated pneumonitis occurred in 3.4% (9/263) of patients receiving OPDIVO: Grade 3 (n=1) and Grade 2 (n=8).
Immune-Mediated Colitis
OPDIVO can cause immune-mediated colitis. 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 monotherapy for Grade 2 or 3 and permanently discontinue for Grade 4 or recurrent colitis upon re-initiation of OPDIVO. When administered with YERVOY, withhold OPDIVO and YERVOY for Grade 2 and permanently discontinue for Grade 3 or 4 or recurrent colitis. In patients receiving OPDIVO monotherapy, immune-mediated colitis occurred in 2.9% (58/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated colitis occurred in 26% (107/407) of patients including three fatal cases.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal (diarrhea of =7 stools above baseline, fever, ileus, peritoneal signs; Grade 3-5) immune-mediated enterocolitis occurred in 34 (7%) patients. Across all YERVOY-treated patients in that study (n=511), 5 (1%) developed intestinal perforation, 4 (0.8%) died as a result of complications, and 26 (5%) were hospitalized for severe enterocolitis.
Immune-Mediated Hepatitis
OPDIVO can cause immune-mediated hepatitis. Monitor patients for abnormal liver tests prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater transaminase elevations. Withhold for Grade 2 and permanently discontinue for Grade 3 or 4 immune-mediated hepatitis. In patients receiving OPDIVO monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated hepatitis occurred in 13% (51/407) of patients.
For full article, please click here.
