LUME-Meso Phase II/III clinical trial

Phase II part (results reported):²

Patients with unresectable MPM (≥18 years old)

Histologically confirmed epithelioid or biphasic MPM

Measurable disease according to modified Response Evaluation Criteria In Solid Tumors

No prior first-line therapies for MPM

Life expectancy ≥3 months

Eastern Cooperative Oncology Group performance status of 0 or 1

N=87

Overall, 87 patients were randomised 1:1 to receive nintedanib plus chemotherapy or placebo plus chemotherapy

Phase III part (ongoing):³

Patients with unresectable MPM (≥18 years old)

Histologically confirmed epithelioid MPM

Measurable disease according to modified Response Evaluation Criteria In Solid Tumours

No prior first-line therapies for MPM

Life expectancy ≥3 months

Eastern Cooperative Oncology Group performance score of 0–1

Planned N=450

Randomisation 1:1 to receive nintedanib plus chemotherapy or placebo plus chemotherapy

Phase II (results reported)² 

Primary outcome measure:

Progression-free survival (PFS)

Secondary outcome measure:

Overall survival (OS)

Objective response rate (ORR)

Phase III (ongoing)³

Primary outcome measure:

PFS

Key secondary outcome measure:

OS

Secondary outcome measures:

ORR

Disease control rate

Health-related quality of life

Phase II (completed)²

PFS by investigator assessment according to mRECIST:²

There was an increase in PFS favouring nintedanib vs placebo in the overall patient population at the primary analysis with 69 PFS events (median PFS: 9.4 vs 5.7 months; hazard ratio [HR]=0.56; 95% confidence interval [CI]: 0.34–0.91; p=0.017) and the updated analysis with 72 PFS events (median PFS: 9.4 vs 5.7 months; HR=0.54; 95% CI: 0.33–0.87; p=0.010). This increase in PFS favouring nintedanib was also seen in patients with epithelioid histology at primary analysis with 60 PFS events (median PFS: 9.7 vs 5.7 months; HR=0.51; 95% CI: 0.30–0.86; p=0.10) and in the updated analysis with 63 PFS events (median PFS: 9.7 [n=39] vs 5.7 months [n=38]; HR=0.49; 95% CI: 0.30–0.82; p=0.006).

OS:²

There was an increase in OS favouring nintedanib vs placebo in the overall population (median OS: 18.3 vs 14.2 months; HR=0.77; 95% CI: 0.46–1.29; p=0.319) and in patients with epithelioid histology (median OS: 20.6 months vs 15.2 months; HR=0.70; 95% CI: 0.40–1.21; p=0.197).

Safety:²

The safety profile of nintedanib plus chemotherapy was as expected from previous studies.

Common side effects (group terms; all grades) were:

• Nausea (nintedanib: 84% vs placebo: 88%)
• Fatigue (nintedanib: 75% vs placebo: 90%)
• Diarrhoea (nintedanib: 71% vs placebo: 37%)
• Neutropenia (nintedanib: 66% vs placebo:29%)
• Electrolyte imbalance (nintedanib: 57% vs placebo: 39%)
• Infection (nintedanib: 55% vs placebo: 51%)
• Vomiting (nintedanib: 55% vs placebo: 51%)

Grade ≥3 adverse events were reported in 80% of patients in the nintedanib arm and 54% of patients in the placebo arm. There was an increased frequency of Grade ≥3 group-term adverse events of neutropenia in the nintedanib arm (43% vs 12%), although the rate of febrile neutropenia (group term) was low in the nintedanib arm (4.5%; n=2) and no febrile neutropenia was reported in the placebo arm. Serious adverse events occurred in 41% of patients in the nintedanib arm and 42% of patients in the placebo arm. The incidence rates of adverse events commonly associated with anti-angiogenic agents were either balanced between treatment arms or lower in the nintedanib arm. Nintedanib did not compromise delivery of chemotherapy.

The addition of nintedanib to standard chemotherapy demonstrated a clinically meaningful benefit in the first-line treatment of patients with unresectable MPM, and a benefit was observed in patients with epithelioid histology. The global Phase III part of this trial is ongoing to confirm the activity of nintedanib in patients with unresectable epithelioid MPM.