FDA Pipeline: Updates on Treatments in NSCLC and Lymphomas, Plus New Dosimetry Software


The U.S. Food and Drug Administration (FDA) recently granted the following application, designations, and clearance:

sBLA for Atezolizumab Plus Chemotherapy for First-Line Treatment of Metastatic, Nonsquamous NSCLC

On January 17, the FDA accepted a supplemental biologics license application (sBLA) for atezolizumab in combination with nanoparticle albumin–bound (nab)-paclitaxel and carboplatin for first-line treatment of patients with metastatic, nonsquamous non–small cell lung cancer (NSCLC) who do not have EGFR or ALK genomic tumor aberrations. The FDA is expected to make a decision on approval by September 2, 2019.

Atezolizumab is a monoclonal antibody designed to bind the programmed cell death ligand 1 (PD-L1) expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both programmed cell death protein 1 (PD-1) and B7.1 receptors. By inhibiting PD-L1, atezolizumab may enable the activation of T cells.

This sBLA is based on results from the phase III IMpower130 study, which met its co-primary endpoints of overall survival and progression-free survival in the initial treatment of people with metastatic nonsquamous NSCLC.

IMpower130’s interim analysis showed that patients treated with atezolizumab plus chemotherapy had a median overall survival of 18.6 months vs 13.9 months in patients treated with chemotherapy alone (hazard ratio [HR] = 0.79; 95% confidence interval [CI] = 0.64–0.98; P = .033) in the intention-to-treat wild-type population. The atezolizumab-based combination also had a median progression-free survival of 7.0 months compared to 5.5 months with chemotherapy alone (HR = 0.64; 95% CI = 0.54–0.77; P < .0001) in the intention-to-treat wild-type population. 

Safety for the atezolizumab-plus-chemotherapy combination appeared consistent with the known safety profiles of the individual medicines, and no new safety signals were identified with the combination. Grade 3 or 4 treatment-related adverse events were reported in 73.2% of people receiving atezolizumab plus chemotherapy compared to 60.3% of people receiving chemotherapy alone.

Breakthrough Therapy Designation for Zanubrutinib in Mantle Cell Lymphoma

The FDA recently granted Breakthrough Therapy designation for zanubrutinib for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. Zanubrutinib (BGB-3111) is an investigational small-molecule inhibitor of Bruton’s tyrosine kinase that is currently being evaluated in a broad pivotal clinical program globally as a monotherapy and in combination with other therapies to treat various B-cell malignancies.

Clinical trials of zanubrutinib include a fully enrolled, global phase III clinical trial in patients with Waldenström’s macroglobulinemia comparing zanubrutinib to ibrutinib, currently the only approved Bruton’s tyrosine kinase inhibitor for Waldenström macroglobulinemia; a global phase III clinical trial in patients with previously untreated chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL); a pivotal phase II trial in patients with relapsed or refractory follicular lymphoma in combination with obinutuzumab; a phase III trial comparing zanubrutinib to ibrutinib in patients with relapsed or CLL/SLL; and a global phase I trial.

Fast Track Designation for IPH410 in Sézary Syndrome

On January 29, the FDA granted Fast Track designation to IPH4102 for the treatment of adult patients with relapsed or refractory Sézary syndrome who have received at least two prior systemic therapies. IPH4102 is an anti-KIR3DL2 antibody, developed for the treatment of T-cell lymphoma. KIR3DL2 is an inhibitory receptor of the KIR family, expressed by approximately 65% of patients across all cutaneous T-cell lymphoma (CTCL) subtypes and expressed by up to 85% of them with certain aggressive CTCL subtypes.

Sézary syndrome is the leukemic variant of CTCL, a heterogeneous group of non-Hodgkin lymphomas that arise primarily in the skin. Patients often experience very poor quality of life with severe and debilitating pruritus. Despite recent advancements, Sézary syndrome is associated with a high relapse rate with currently available therapies.

Fast Track designation is based on preliminary results of the phase I dose-escalation and expansion study of IPH4102 in advanced CTCL. As of October 15, 2018, data from the subgroup of 35 patients with Sézary syndrome revealed strong clinical activity, demonstrated by an overall response rate of 42.9%, median duration of response of 13.8 months, and median progression-free survival of 11.7 months. The overall response rate appeared to be higher (n = 28, 53.6%) in patients with no histologic evidence of large cell transformation.

Importantly, clinical activity was associated with a substantial improvement in quality of life as assessed by the SkinDex29 and Pruritus Visual Analog Scale scores. IPH4102 displayed a favorable safety profile, consistent with previous observations.

510(k) Clearance for Molecular Radiotherapy Dosimetry

MIM Software Inc has announced it received 510(k) clearance from the FDA for molecular radiotherapy (MRT) dosimetry.

Molecular radiotherapy is an effective form of therapy that uses radiopharmaceuticals such as Lu-177 dotatate and I-131 iobenguane to target tumors based on certain receptors that these tumors express. Until now, there has not been an effective way to measure the absorbed dose from MRT for an individual patient. This is due to a lack of access to quantitative single-photon emission computed tomography (SPECT) images and tools for calculating dose on the patient’s own anatomy.

MIM SurePlan MRT provides both quantitative SPECT reconstruction and voxel-based absorbed dose calculation by utilizing the patient's own images, allowing for personalized dosimetry measurements. The software provides timesaving tools for organ and tumor segmentation, deformable registration, and voxel-based dosimetry for molecular radiotherapy. Other features of MIM SurePlan MRT include multitracer theranostics support, quantitative SPECT and planar corrections, and dosimetry reporting tools.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.