Barbara Boughton

A regimen of pembrolizumab (Keytruda) and low-dose ipilimumab (Yervoy) was effective, and tolerable, for patients with advanced melanoma, according to results from the phase Ib KEYNOTE-029 clinical trial presented by lead investigator Georgina Long, BSc, PhD, MBBS.

The trial included 72 patients with advanced melanoma followed for 18 weeks. Patients were treated in the United States, New Zealand, or Australia with pembrolizumab at 2 mg/kg and four doses of ipilimumab at 1 mg/kg. Of the patients, 9 (12%) had been previously treated, none with checkpoint inhibitor therapies. The study showed an overall response rate (ORR) of 56%, said Long, medical oncologist at the Melanoma Institute, Australia, during the late-breaking abstract session at the 2015 Society for Melanoma Research Congress.

The combination showed a rate of grade 3/4 adverse events (AEs) at 36%, with a 54% incidence of immune-mediated AEs. These data were similar to that of other trials exploring the combination of PD-1 and CTLA-4 inhibition, added Long.

Most patients in the KEYNOTE-029 study were male with a median age of 60 years, with 86% being PD-L1 positive. Only 28% of the patients had BRAF V600 mutations. Eighty five percent of patients had a good ECOG performance status of 0, and only 21% had elevated LDH levels.

Among treatment-na&iuml;ve patients (n = 63), the ORR was 57%. Among those who had been previously treated, the ORR was 44%. The disease control rate (ORR plus stable disease) was 79%, noted Long. &ldquo;Only 14 patients in the study, or 19%, were diagnosed with progressive disease,&rdquo; she said.

The complete response rate was 4% across the full study. There were no complete responses in those who had undergone previous therapy, said Long.

Thirty-seven patients (51%) had a partial response to treatment. The partial response rates were 52% and 44% in the treatment-na&iuml;ve and pretreated groups, respectively. Stable disease occurred after treatment in 24% of patients.

Altogether, 72% of the patients received all 4 ipilimumab doses, and only 31% discontinued both treatments before the end of the trial. Most of the discontinuations were due to progression (19%) or AEs (10%), said Long.

&ldquo;The majority of patients with ongoing adverse events experience thyroid-related side effects,&rdquo; Long said. Ninety three percent of patients experienced treatment-related AEs, but only 22% were rated as &ldquo;serious&rdquo; by the investigators. None led to death. Seventeen percent of AEs led to ipilimumab discontinuation before the end of the trial, and 8% of AEs led patients to discontinue both drugs.

The most frequent AE in the KEYNOTE-029 study was rash, which affected 53% of patients. Thirty one percent of patients experienced fatigue and 28% were diagnosed with pruritis during treatment. Seventeen percent of patients experienced hypothyroidism as a result of treatment.

Grade 3 or 4 immune-mediated AEs affected 17% of patients. The most frequent immune-mediated AEs were hypothyroidism, hypophysitis, and hyperthyroidism. Other common immune-mediated AEs were pneumonitis and colitis, Long noted.

&ldquo;Hypophysitis was more common in this trial than we&rsquo;ve seen in similar studies, but it&rsquo;s difficult to say why that occurred,&rdquo; Long said. &ldquo;We were very aware of this side effect during the study, and so that may be one explanation."

The KEYNOTE-029 phase Ib trial was a continuation of a smaller clinical study with the same study medications at the same dosages. Enrollment in the earlier study also included patients with renal cell cancer, said Long. Since only 6 patients in the earlier study experienced dose-limiting toxicity, the trial was expanded to 72 patientsall with advanced melanoma.

The investigators will continue to evaluate the efficacy and safety data resulting from the treatment regimen used in the KEYNOTE-029 trial, noted Long. They plan to analyze these outcomes and correlate them with tumor biomarkers, using an expanded data set of 153 patients, she added.

Long G. KEYNOTE-029: Pembolizumab (pembro) + low-dose ipilimumab (ipi) for advanced melanoma. Presented at the Society for Melanoma Research 2015 Congress; November 18-21, 2015; San Francisco, CA.

Barbara Boughton | Authors

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