publication date: May. 29, 2020

Drugs & Targets

Opdivo + Yervoy receive FDA approval combined with limited chemotherapy as first-line treatment of metastatic or recurrent NSCLC

FDA has approved Opdivo and Yervoy (nivolumab + ipilimumab) in combination with two cycles of platinum-doublet chemotherapy as first-line treatment for patients with metastatic or recurrent non-small cell lung cancer, with no epidermal growth factor receptor or anaplastic lymphoma kinase genomic tumor aberrations.

Opdivo and Yervoy are sponsored by Bristol-Myers Squibb Co.

Efficacy was investigated in CHECKMATE-9LA (NCT03215706), a randomized, open-label trial in patients with metastatic or recurrent NSCLC. Patients were randomized to receive either the combination of nivolumab plus ipilimumab and 2 cycles of platinum-doublet chemotherapy (n=361) or platinum-doublet chemotherapy for 4 cycles (n=358).

The trial demonstrated a statistically significant benefit in overall survival (OS) for patients treated with nivolumab plus ipilimumab plus chemotherapy compared to those who received chemotherapy. Median OS was 14.1 months (95% CI: 13.2, 16.2) versus 10.7 months (95% CI: 9.5, 12.5), HR 0.69; 96.71% CI: 0.55, 0.87).

Median progression-free survival per blinded independent central review (BICR) was 6.8 months (95% CI: 5.6, 7.7) in the nivolumab plus ipilimumab and chemotherapy arm and 5 months (95% CI: 4.3, 5.6) in the chemotherapy arm (HR 0.70; 95% CI: 0.57, 0.86). Confirmed overall response rate (ORR) per BICR was 38% (95% CI: 33, 43) and 25% (95% CI: 21, 30) respectively. Median response duration was 10 months in the nivolumab plus ipilimumab and chemotherapy arm, and 5.1 months in the chemotherapy arm.

FDA collaborated with the Australian Therapeutic Goods Administration, Health Canada, and Singapore’s Health Sciences Authority on the review of this application as part of Project Orbis. FDA approved this application 2 months ahead of schedule. The FDA and HSA decisions are near-simultaneous, while the review of the applications is ongoing for the Australian TGA and Health Canada.

This review used the Real-Time Oncology Review. This application was granted priority review and fast track designation.


Brigatinib receives FDA approval for ALK-positive metastatic NSCLC

Brigatinib (Alunbrig) has received FDA approval for adult patients with anaplastic lymphoma kinase-positive metastatic non-small cell lung cancer as detected by an FDA-approved test.

Alunbrig is sponsored by Ariad Pharmaceuticals Inc.

FDA also approved the Vysis ALK Break Apart FISH Probe Kit (sponsored by Abbott Molecular Inc.) as a companion diagnostic for brigatinib.

Efficacy was investigated in ALTA 1L (NCT02737501), a randomized (1:1), open-label, multicenter trial in adult patients with advanced ALK-positive NSCLC who had not previously received an ALK-targeted therapy. The trial required patients to have an ALK rearrangement based on a local standard of care testing. The trial randomized 275 patients to receive brigatinib 180 mg orally once daily with a 7-day lead-in at 90 mg once daily (n=137) or crizotinib 250 mg orally twice daily (n=138). A subset of the clinical samples was retrospectively tested with the Vysis ALK Break Apart FISH Probe Kit. Of the enrolled patients, 239 had positive results using the Vysis diagnostic test (central results were negative for 20 patients and unavailable for 16 patients).

The major efficacy outcome measure was progression-free survival evaluated by a blinded independent review committee according to RECIST 1.1. Additional efficacy outcome measures as evaluated by the BIRC was confirmed overall response rate.

Estimated median PFS for patients treated with brigatinib was 24 months (95% CI: 18.5, NE) compared with 11 months (95% CI: 9.2, 12.9) for those treated with crizotinib (HR 0.49; 95% CI: 0.35, 0.68; p<.0001). Confirmed ORR was 74% (95% CI: 66, 81) and 62% (95% CI: 53, 70), respectively.


CLR 131 receives fast track designation in lymphoplasmacytic lymphoma/Waldenstrom’s macroglobulinemia

CLR 131 was granted FDA Fast Track Designation in lymphoplasmacytic lymphoma (LPL)/Waldenstrom’s macroglobulinemia in patients having received two prior treatment regimens or more.

CLR 131 is sponsored by Cellectar Biosciences Inc.

CLR 131 is a small-molecule, cancer-targeting radiotherapeutic Phospholipid Drug Conjugate designed to deliver cytotoxic radiation directly and selectively to cancer cells and cancer stem cells. It is being evaluated in Cellectar’s phase II CLOVER-1 clinical study in patients with relapsed or refractory multiple myeloma and lymphoplasmacytic lymphoma/Waldenstrom’s macroglobulinemia.

“LPL/WM patients that do not respond optimally or are intolerant of ibrutinib, currently have limited treatment options and poor survival rates,” James Caruso, president and CEO of Cellectar, said in a statement.

All four LPL/WM patients treated in our CLOVER-1 phase II study to date achieved a 100% overall response rate and a 25% complete response rate.

“This strong response rate may represent an important improvement in the treatment of relapsed/refractory LPL/WM as no approved or late-stage development treatments for relapsed or refractory patients have reported complete responses,” Caruso said.

FDA granted CLR 131 in LPL Orphan Drug Designation earlier this year.

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