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NGR015

NGR-hTNF in combination with best investigator choice in previously treated malignant pleural mesothelioma (NGR015): a randomised, double-blind, placebo-controlled phase 3 trial

Phase 3N = 400NCT01098266

Population
Adults with malignant pleural mesothelioma of any histological subtype, ECOG performance status 0-2, and radiologically documented progressive disease after one pemetrexed-based chemotherapy regimen.
Design
Randomised (1:1, block size four), double-blind, placebo-controlled phase 3 trial at 41 centres in 12 countries: weekly NGR-hTNF 0.8 μg/m2 intravenously plus best investigator choice, or placebo plus best investigator choice. Best investigator choice, decided before randomisation, was single-agent gemcitabine, vinorelbine or doxorubicin, or best supportive care only. Stratified by performance status and best investigator choice. Primary endpoint overall survival in the ITT population; cutoff 29 April 2014. Enrolment 12 April 2010 to 21 January 2013.
Primary endpoint
OS
Arms
  • NGR-hTNF plus best investigator choice (experimental, n = 200): Weekly NGR-hTNF 0.8 μg/m2 intravenously plus best investigator choice
  • Placebo plus best investigator choice (control, n = 200): Placebo plus best investigator choice
People
Gregorc V
OSHR 0.94 (95% CI 0.75–1.18)Δ median OS+0.5 months
Show the numbers
Results reported for NGR015
EndpointAnalysisNGR-hTNF plus best investigator choicePlacebo plus best investigator choiceEffect
OSprimarymedian follow-up 18.7 monthsGregorc 2018median 8.5 months (7.2–9.9)median 8 months (6.6–8.9)HR 0.94 (95% CI 0.75–1.18)P=0.58Median follow-up 18.7 months (IQR 15.1-24.4). 381 (95%) of 400 patients were selected to receive chemotherapy before randomisation. Grade 3 or worse study-emergent adverse events occurred in 136 (70%) patients with NGR-hTNF and 118 (61%) with placebo. The authors state that the study did not meet its primary endpoint.
Results reported for NGR015
EndpointAnalysisNGR-hTNF plus best investigator choicePlacebo plus best investigator choiceEffect
OSprimarymedian follow-up 18.7 monthsGregorc 2018median 8.5 months (7.2–9.9)median 8 months (6.6–8.9)HR 0.94 (95% CI 0.75–1.18)P=0.58Median follow-up 18.7 months (IQR 15.1-24.4). 381 (95%) of 400 patients were selected to receive chemotherapy before randomisation. Grade 3 or worse study-emergent adverse events occurred in 136 (70%) patients with NGR-hTNF and 118 (61%) with placebo. The authors state that the study did not meet its primary endpoint.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
OS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
OS0.940.75–1.18
Illustrative — modelled from reported values, not trial data. OS, primary.
0%25%50%75%100%05101520Months (modelled)
  • NGR-hTNF plus best investigator choice (experimental)
  • Placebo plus best investigator choice (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsNGR-hTNF plus best investigator choicePlacebo plus best investigator choice
0100.0%100.0%
566.5%64.8%
1140.8%38.6%
1627.1%25.0%
2118.0%16.2%
Primary publication: Gregorc V, Gaafar RM, Favaretto A, Grossi F, Jassem J, Polychronis A, et al. NGR-hTNF in combination with best investigator choice in previously treated malignant pleural mesothelioma (NGR015): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2018;19(6):799-811. PubMedDOI

Appears in

Sources

  1. Gregorc V, Gaafar RM, Favaretto A, Grossi F, Jassem J, Polychronis A, et al. NGR-hTNF in combination with best investigator choice in previously treated malignant pleural mesothelioma (NGR015): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2018;19(6):799-811.

    PubMedDOI