Pneumologie 2011; 65 - V125
DOI: 10.1055/s-0031-1272244

A randomized phase IItrial of mapatumumab, a TRAIL R1 agonist monoclonal antibody, in combination with carboplatin and paclitaxel in patients with advanced NSCLC

J von Pawel 1, J Harvey 2, D Spigel 3, M Dediu 4, M Reck 5, C Cebotaru 6, E Kumm 7, G Gallant 7, N Fox 7, D Camidge 8
  • 1Asklepios-Fachkliniken München-Gauting
  • 2Birmingham, AL
  • 3Nashville, TN
  • 4Bucharest
  • 5Krankenhaus Grosshansdorf, Innere Medizin
  • 6Cluj
  • 7Rocksville, MD
  • 8Aurora, CO

Aims: Mapatumumab, a fully human agonist mab, targets and activates the death receptor TRAIL-R1. We conducted a randomized, controlled phase II trial to evaluate mapatumumab in combination with carboplatin and paclitaxel as first-line therapy in advanced non-small call lung cancer (NSCLC). Methods: Patients were required to have histol. or cytol. confirmed Stage IIIB or IV advanced primary NSCLC with measurable disease by RECIST. Patients were randomly assigned to Arm A, paclitaxel 200mg/m2 + carboplatin AUC 6.0 (PC);Arm B, PC + mapatumumab 10mg/kg; or Arm C, PC + mapatumumab 30mg/kg. Cycles were repeated every 21 days; patients completed up to 6 cycles in the absence of evidence of disease progression or unacceptable toxicity. Patients in Arms B and C could receive additional cycles of mapatumumab in the absence of disease progression. The co-primary endpoints were response rate (RR; complete response + partial response) and progression-free survival (PFS). Images were read by independent radiologists blinded to treatment group assignment, as well as locally. Results: 111 patients were enrolled at 22 sites in 4 countries. Addition of mapatumumab to PC did not improve RR or PFS. RR and PFS, based on the independent read, and overall survival results are summarized below. The results based on local reading also showed no benefit from the addition of mapatumumab to PC.AE's were generally balanced across treatment groups; there was no evidence that mapatumumab exacerbated toxicities associated with PC. Conclusions: The results do not support further evaluation of mapatumumab in combination with PC in patients with advanced NSCLC. Additional trials of mapatumumab in other indications are ongoing.

Table 1

Arm A (n=36)

Arm B (n=37)

Arm C (n=36)

RR (n,%)

11 (30.6)

5 (13.5)
p=0.0785a

13 (36.1)
p=0.6171b

Median PFS (mos, 95% CI)

4.6 (4.1, 5.6)

4.6 (2.8, 5.6)
p=0.8621a

4.9 (1.7, 5.5)
p=0.9387b

Median overall survival (mos, 95% CI)

10.5 (7.3, 15.2)

13.6 (9.8, NA)
p=0.3622a

10.6 (6.2, NA)
p=0.9745b