Supplemental Table 1. Other Agents Targeting Proapoptotic Death Receptors in Clinical Development for the Treatment of
Lung Cancer
Clinical
Development
Agent
Target
Phase
Setting
Treatment Groups
N
Key Results
Drozitumab
(PRO95780)
2 DLTs; treatment appeared
well- tolerated; no objective
responses
Phase 12
Second
line or
greater
Drozitumab 1–20 mg/kg
First line
PC vs PC + dulanermin
8 mg/kg vs PCB vs PCB
+ dulanermin 8 mg/kg vs
PCB + dulanermin
20 mg/kg
First line
PCB + dulanermin 4–
20 mg/kg
24
Treatment appeared welltolerated; overall response
rate 58% (1 CR, 13 PR)
Second
line or
greater
Mapatumumab 10 mg/kg
32
Treatment appeared welltolerated; no objective
responses (9 SD)
Second
line or
greater
Lexatumumab 0.1, 1, or
3 mg/kg
DR5
DR4,
DR5
DR4
50
(3 with lung
cancer)
Drozitumab + PCB vs
placebo +PCB
Phase 1b
Mapatumumab
(HGS-ETR1;
TRM-1)
No significant differences in
outcomes
First line
Phase 23
Dulanermin
(AMG 951)
124
Phase 21
4
Phase 25
213
Addition of dulanermin to PC
or PCB did not improve
outcomes in unselected
patients
Treatment appeared welltolerated; no objective
responses (9 SD)
Treatment appeared wellTigatuzumab
PC
±
tigatuzumab
10
tolerated; addition of
DR5
Phase 27
First line
100
(CS-1008)
mg/kg
tigatuzumab to PC did not
improve outcomes
CR=complete response; DLT=dose-limiting toxicity; NSCLC=non–small-cell lung cancer; PC=paclitaxel and carboplatin; PCB= PC
plus bevacizumab; PR=partial response; RCT=randomized, controlled trial.
Lexatumumab
(HGS-ETR2)
1.
DR5
Phase 16
31
(8 with
NSCLC)
Karapetis CS, Clingan PR, Leighl NB, et al. Phase II study of PRO95780 plus paclitaxel, carboplatin, and bevacizumab (PCB)
in non-small cell lung cancer (NSCLC) [abstract]. J Clin Oncol 2010;28:7535.
2.
Camidge DR, Herbst RS, Gordon MS, et al. A phase I safety and pharmacokinetic study of the death receptor 5 agonistic
antibody PRO95780 in patients with advanced malignancies. Clin Cancer Res 2010;16:1256-1263.
3.
Soria JC, Mark Z, Zatloukal P, et al. Randomized phase II study of dulanermin in combination with paclitaxel, carboplatin, and
bevacizumab in advanced non-small-cell lung cancer. J Clin Oncol 2011;29:4442-4451.
4.
Soria JC, Smit E, Khayat D, et al. Phase 1b study of dulanermin (recombinant human Apo2L/TRAIL) in combination with
paclitaxel, carboplatin, and bevacizumab in patients with advanced non-squamous non-small-cell lung cancer. J Clin Oncol
2010;28:1527-1533.
5.
Greco FA, Bonomi P, Crawford J, et al. Phase 2 study of mapatumumab, a fully human agonistic monoclonal antibody which
targets and activates the TRAIL receptor-1, in patients with advanced non-small cell lung cancer. Lung Cancer 2008;61:82-90.
6.
Wakelee HA, Patnaik A, Sikic BI, et al. Phase I and pharmacokinetic study of lexatumumab (HGS-ETR2) given every 2 weeks
in patients with advanced solid tumors. Ann Oncol 2010;21:376-381.
7.
Von Pawel J, Hadler D, Fox T, et al. A randomized, double-blind, placebo-controlled phase II study of tigatuzumab (CS-1008)
in combination with carboplatin/paclitaxel in patients with chemotherapy-naive metastatic/unresectable non-small cell lung
cancer (NSCLC) [abstract]. J Clin Oncol 2012;30:7536.