Priority Review Designation in PMBCL and 2017 SABCS, ASH Annual Meeting Highlights

Today-

A priority review designation in primary mediastinal large B-cell lymphoma, promising results in non—small cell lung cancer and renal cell carcinoma trials, and highlights from the San Antonio Breast Cancer Symposium and the ASH Annual Meeting and Exposition.

Welcome to OncLive News Network! I’m Gina Columbus.

The FDA has granted a priority review to a supplemental biologics license application for pembrolizumab as a treatment for adult and pediatric patients with relapsed/refractory primary mediastinal large B-cell lymphoma.

The application was based on findings from a cohort of the phase II KEYNOTE-170 trial, which evaluated the anti—PD-1 agent in 29 patients with PMBCL.

At a median follow-up of 10.5 months, pembrolizumab was associated with an overall response rate of 41% by blinded independent central review and 38% by investigator review. Additionally, there was a 24% complete response rate and a 17% partial response rate. The median time to response was 2.8 months, and the median duration of response was not reached. Twelve-month overall survival was 62% and median OS was not reached.

Under the Prescription Drug User Fee Act, the FDA is scheduled to decide on the approval by April 3, 2018.

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In non—small cell lung cancer, results of the phase III IMpower150 trial demonstrated that treatment with the combination of atezolizumab, bevacizumab, carboplatin, and paclitaxel delayed progression or death by 38% versus bevacizumab and chemotherapy alone for patients with advanced nonsquamous disease.

This is the first phase III trial to report on the combination of chemotherapy, antiangiogenic treatment and immunotherapy as first-line treatment for advanced non-squamous NSCLC.

The study’s findings, which were presented at the ESMO Immuno Oncology Congress, showed that the atezolizumab regimen was associated with a median progression-free survival of 8.3 months compared with 6.8 months with bevacizumab and chemotherapy alone. The 12-month PFS rate was 37% with the atezolizumab-containing regimen and 18% with the bevacizumab/chemotherapy arm.

Additional results showed that, in preliminary examination of overall survival, there was a 22.5% reduction in the risk of death with the atezolizumab combination versus bevacizumab and chemotherapy alone. After a minimum follow-up of 9.5 months, the median OS was 14.4 versus 19.2 months, in favor of the atezolizumab group. The next OS analysis will take place in the first half of 2018.

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In renal cell carcinoma, the combination of atezolizumab and bevacizumab was associated with a statistically significant reduction in the risk for death or disease progression in patients with PD-L1—positive advanced or metastatic disease.

The combination met the co-primary endpoint for investigator-assessed progression-free survival in the phase III IMmotion151 trial, which evaluated the efficacy and safety of atezolizumab and bevacizumab versus sunitinib for patients who have not received prior systemic therapy.

Genentech, the manufacturer of both agents, did not release any data from the trial, adding that initial results will be presented at a medical conference next year. Top-line results for OS are not mature.

Results from the phase II IMmotion 150 trial were presented in September at the 2017 ESMO Congress, which showed that the median progression-free survival by RECIST criteria was 7.8 months with sunitinib, 5.5 months with atezolizumab monotherapy, and 11.0 months with the combination. By immune-modified RECIST criteria, median PFS was 9.9 months with sunitinib, 8.5 months with atezolizumab monotherapy, and 17.3 months with atezolizumab and bevacizumab.

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The 2017 San Antonio Breast Cancer Symposium took place in Texas over the past week, highlighting some of the latest clinical trial findings in the field.

First, phase III results of the MONALEESA-7 trial showed that adding ribociclib to standard endocrine therapy with temporary ovarian suppression significantly improved progression-free survival as a first-line treatment for pre- and perimenopausal women with advanced HR-positive/HER2-negative breast cancer. This marks the first time that a CDK4/6 inhibitor is effective in younger patients who currently have few treatment options.

The median PFS was 23.8 months for women who received ribociclib in combination with either tamoxifen or a nonsteroidal aromatase inhibitor and goserelin versus 13.0 months for those who received the standard endocrine therapy plus placebo.

Second, the combination of pembrolizumab and trastuzumab showed an objective response rate of 15.2% in patients with trastuzumab-resistant, PD-L1—positive, HER2-positive breast cancer in the phase Ib/II PANACEA trial. Moreover, there was a disease control rate of 24% in PD-L1–positive patients.

Finally, results of the ABCSG-16 phase III trial demonstrated that years can safely be shaved off treatment with anastrozole without affecting disease-free survival for patients with postmenopausal hormone receptor-positive breast cancer.

Additionally, shorter treatment spans can significantly reduce bone fractures, which is a common side effect of aromatase-inhibitor therapy.

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Following SABCS, the ASH Annual Meeting was held in Atlanta, Georgia, showcasing pivotal findings with novel treatment approaches across hematologic malignancies.

In multiple myeloma, treatment with the BCMA-directed CAR T-cell therapy bb2121 induced complete remissions for 56% of patients with relapsed/refractory disease. The objective response rate was 94%, which consisted of a very good partial response or better for 89% of patients. After 40 weeks of follow-up, the median progression-free survival had not yet been reached. The 9-month PFS rate was 71%. The treatment was generally well tolerated and the manufacturing success rate was 100%.

Next, early treatment using induction therapy with carfilzomib, lenalidomide, and dexamethasone followed by high-dose therapy and autologous stem cell transplantation, consolidation therapy and then maintenance therapy with lenalidomide and dexamethasone for patients with smoldering multiple myeloma was found to elicit durable responses. At a median follow-up of 10 months in the single-arm study, the PFS and overall survival were 94% and 98%, respectively, at 28 months.

Additionally, findings from the TAP CLARITY study found that the combination of ibrutinib and venetoclax elicited a complete response or CR with incomplete hematologic recovery rate of 47% for patients with relapsed/refractory chronic lymphocytic leukemia.

In the 38 efficacy-evaluable patients, all experienced at least a partial response to the combination of ibrutinib and venetoclax, leading to an objective response rate of 100%.

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This week during the ASH Annual Meeting, we sat down with Dr Michael Wang, MD, at The University of Texas MD Anderson Cancer Center to discuss results from the phase II ACE-LY-004 trial, which explored the BTK inhibitor acalabrutinib in patients with refractory mantle cell lymphoma.

That’s all for today.

Thank you for watching OncLive News Network! I’m Gina Columbus.