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Immune System Booster Pembrolizumab Effective in Skin, Lung Cancer in Early Study

Treatment shrinks tumors in both cohorts

Preliminary data from a large early-stage trial have indicated that the investigational immunotherapy pembrolizumab (Merck) is effective in patients with melanoma or lung cancer.

The new data were presented June 2 at the 50th annual meeting of the American Society of Clinical Oncology (ASCO 2014), held in Chicago, Illinois.

The phase Ib KEYNOTE-001 trial is an ongoing, single-arm, open-label study evaluating pembrolizumb, an investigational anti–programmed death-1 (PD-1) antibody, in more than 1,000 patients with diverse late-stage (metastatic) cancers — predominantly melanoma and lung cancer. Three dosing regimens of pembrolizumab are being evaluated, including 10 mg/kg every 2 weeks, 10 mg/kg every 3 weeks, and 2 mg/kg every 3 weeks. The study’s primary endpoint includes the overall response rate (ORR)and safety. Secondary endpoints include progression-free survival (PFS), overall survival (OS), and the duration of response.

A total of 411 patients with advanced melanoma are being evaluated. The study involves seven advanced-melanoma cohorts, including patients with varying stages of disease and prior lines of therapy. At baseline, 56% of the patients had the most advanced stage of disease (M1c; n = 232) and 77% of the patients had received at least one prior systemic therapy (n = 316).

After treatment with pembrolizumab, the estimated OS rate at 1 year was 69% across all patients studied, including 74% of patients without prior ipilimumab therapy (current standard therapy) and 65% of patients who had progressive disease during or after treatment with ipilimumab. At 18 months, the estimated OS was 62%. The median OS has not been reached, with some patients receiving treatment with pembrolizumab as monotherapy for more than 2 years.

In patients with measurable disease at baseline who had received at least one treatment scan, 72% (227/317) showed tumor shrinkage, including 39% (123/317) who had tumor shrinkage of greater than 50% by Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1). Based on immune-related response criteria (irRC), 64% (204/319) of patients showed tumor shrinkage, including 31% (100/319) who showed tumor shrinkage of greater than 80%.

Based on these preliminary results, the recommended dose proposed for pembrolizumab in patients with advanced melanoma is 2 mg/kg once every 3 weeks.

In the same trial, initial therapy with pembrolizumab is being evaluated in a cohort of patients with PD-1 ligand (PD-L1)–positive, advanced NSCLC. Tumor response in these patients is being assessed every 9 weeks by irRC and RECIST 1.1.

In previously untreated patients, the ORR with pembrolizumab as monotherapy was 47% by irRC (21/45) and 26% by RECIST 1.1 (11/42). In evaluable patients who had measurable disease with one post-baseline scan, 80% (28/35) demonstrated tumor shrinkage, as measured by RECIST 1.1. The median duration of response has not been reached, with some patients continuing on treatment with pembrolizumab as monotherapy for at least 1 year.

The interim median PFS was 37 weeks by irRC and 27 weeks by RECIST 1.1. The interim median duration of treatment among evaluable patients with ongoing responses was 27.1 weeks, based on both measurement criteria.

Pembrolizumab is an investigational, selective, humanized, monoclonal anti–PD-1 antibody designed to block the interaction of PD-1 with its ligands, PD-L1 and PD-L2, on T-cells to reactivate anti-tumor immunity. Pembrolizumab exerts dual ligand blockade of the PD-1 pathway. The drug is being evaluated in more than 30 types of cancers as monotherapy and as part of combination treatments.

Sources: Merck: Melanoma; June 2, 2014; and Merck: NSCLC; June 2, 2014.

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