Pegilodecakin Plus PD-1 Inhibitor Shows Potential in NSCLC

Edward B. Garon, MD, associate professor of oncology and urology at Johns Hopkins Medicine

Edward B. Garon, MD

Combining pegilodecakin (AM0010) with nivolumab (Opdivo) or pembrolizumab (Keytruda) induced an overall response rate (ORR) of 41% in patients with advanced non—small cell lung cancer (NSCLC), according to findings from an early phase study presented at the 2018 ASCO Annual meeting.

At a median follow-up of 24.7 months (range, 9.1-39.1), partial responses were observed in 11 of 27 evaluable patients who received pegilodecakin plus a PD-1 inhibitor. An additional 12 patients had stable disease.

The median overall survival (OS) was 32.2 months in the patients who received pegilodecakin/pembrolizumab and the median progression-free survival (PFS) was 11 months. The median OS and PFS have not yet been reached for the cohort of patients receiving pegilodecakin plus nivolumab.

“Pegilodecakin when added to anti—PD-1 therapy in advanced NSCLC patients was associated with response rates and durability of benefit greater than has been seen with anti–PD-1 alone,” lead investigator Edward B. Garon, MD, director of Thoracic Oncology at the Jonsson Comprehensive Cancer Center at University of California, Los Angeles, wrote in their poster.

“Responses were seen in settings in which anti—PD-1 therapy has demonstrated limited benefit, such as absent PD-L1 expression, low tumor mutational burden (TMB) and/or the presence of liver metastasis. These preliminary findings support further studies of pegilodecakin with anti–PD-1 therapies,” added Garon et al.

Pegilodecakin is a long-acting PEGylated form of recombinant human Interleukin-10 (IL-10). Explaining the rationale for combining pegilodecakin with a PD-1 inhibitor, Garon et al wrote, “Anti—PD-1 reactivates the T cell receptor while pegilodecakin stimulates the survival, cytotoxicity, and expansion of intratumoral antigen activated CD8+ T cells.”

The study enrolled 34 previously patients who all received daily pegilodecakin at 10 to 20 µg/kg through subcutaneous administration. Five patients received pegilodecakin in combination with pembrolizumab (2 mg/kg IV every 3 weeks) and 29 patients received the investigational agent in combination with nivolumab (3mg/kg IV every 2 weeks).

The median age in the pembrolizumab group was 74 (range, 56-80), 4 patients were male, and all 5 had an ECOG performance status of 1. Two patients had squamous histology and the other 3 had nonsquamous. The median number of prior therapies was 2 (range, 0-5) and all 4 patients tested for PD-L1 status had a PD-L1 level <1%.

Among the 29 patients receiving nivolumab, the median age was 62 (range, 40-84), 14 were male, and 15 were female. Eight had an ECOG performance status of 0 and 21 had a score of 1. Twenty-four patients had nonsquamous histology, 4 had squamous, and the histology for 1 was unknown. The median number of prior therapies was 2 (range, 0-5).

It was requested that investigators preferentially enroll PD-L1—negative patients. Among the 20 patients evaluable for ORR, 12 (60%) had PD-L1 expression <1% (negative), 3 had expression of 1%-49% (low), and 5 had expression ≥50% (high). Four of the 12 PD-L1–negative patients achieved a partial response. Additionally, 4 of 5 PD-L1–high patients and 1 of 3 PD-L1–low patients had a response.

Among 8 patients with low-to-intermediate TMB (≤243 mutations), 5 had a partial response. Of the 2 patients with high TMB (>243 mutations), 1 had a partial response.

In the subgroup of 6 patients who tested negative on interferon associated mRNA Expression Profile (GEP), 2 had partial responses. Five of 8 patients with liver metastasis had partial responses.

Safety data were provided across 29 patients who received pegilodecakin at 20 µg/kg plus either pembrolizumab or nivolumab. Grade 3/4 treatment-related adverse events included anemia (n = 5), thrombocytopenia (n = 5), fatigue (n = 5), pyrexia (n = 2), febrile neutropenia (n = 1), international normalized ratio increased (n = 1), hypertriglyceridemia (n = 3), neck pain (n = 1), pneumonitis (n = 1), rash (n = 1), and maculopapular rash (n = 2).

The 1 grade 3/4 immune-related adverse event was pneumonitis. The recommended phase II dose is 10 µg/kg daily.

Commenting on the data in a poster session at ASCO, D. Ross Camidge, MD, PhD,professor, division of Medical Oncology, Joyce Zeff Chair in Lung Cancer Research, University of Colorado, said the data are positive, but the small number of patients necessitate a randomized trial to confirm the early signs of efficacy.

“Pegilodecakin plus PD-1 inhibition was associated with a greater response rate than is anticipated with PD-1 inhibition alone; however, the small number of patients in the cohorts [should be noted],” said Camidge, adding, “It is easier to be impressed by the activity in the lower PD-L1 groups, as the high PD-L1 groups are still within the ‘chance effect,’ given the small number of patients.”

Garon EB, Schneider JG, Wong DJL, et al. Responses and durability in NSCLC treated with pegilodecakin and anti-PD-1. J Clin Oncol. 2018;36 (suppl; abstr 9018).

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