Results of Three Phase II Trials in Lung Cancer Indications Confirm Safety and Antitumour Activity of NGR-hTNF

S.p.A. reports new clinical data of its investigational anticancer drug NGR-hTNF in three different lung cancer indications, which will be presented on 4 June at the 47th ASCO Annual Meeting in Chicago. Initial analysis of a randomized Phase II trial in non-small cell lung cancer, along with top line results of a Phase II trial in small-cell lung cancer and long-term follow up of a Phase II trial in mesothelioma, confirm the favourable safety profile as well as the promising antitumour activity of NGR-hTNF.

Claudio Bordignon, MolMed's chairman and CEO, comments: "These new data represent another important milestone in the development of NGR-hTNF and show our commitment in the treatment of pulmonary tumours, from mesothelioma to non-small cell and small cell lung cancers. These are the results of a intense and diversified effort in clinical development: we have now ongoing several trials including a pivotal Phase III trial in mesothelioma and a randomized Phase II trial in non-small cell lung cancer. In the treatment of mesothelioma, we expect to have the final results of the Phase III study in 2013, while the results of the long-term analysis of the completed Phase II study confirm the efficacy of our treatment-intensification strategy.”

Bordignon continued, “In non-small cell lung cancer, the first evaluation of the randomized Phase II trial suggests antitumour activity that is particularly evident in patients with squamous histology, and in patients with adenocarcinoma who received maintenance treatment with NGR-hTNF after completion of chemotherapy. These are important results, because this evidence, together with the lack of cumulative toxicity, led us to explore a new treatment option for NGR-hTNF as maintenance therapy. The first application of this new approach is represented by a randomized Phase II trial of first-line therapy in mesothelioma now open for patient accrual."

• First results of a randomized Phase II trial of NGR-hTNF in combination with cisplatin-based chemotherapy as first-line treatment for non-small cell lung cancer (ASCO abstract 7568). This ongoing trial is investigating the impact of NGR-hTNF in combination with cisplatin-based chemotherapy. So far, 80 patients have been assessed for safety and preliminary antitumour activity. As far as safety is concerned, there were no pulmonary haemorrhage or bleeding events, which have been commonly associated with the use of antiangiogenic agents in patients with squamous histology.

First data on clinical activity are promising; there is evidence of improved activity in terms of disease control and duration of progression-free survival in patients either with squamous or non-squamous histology who continued treatment with NGR-hTNF alone as maintenance therapy after completion of chemotherapy, thus confirming the effect of NGR-hTNF in long-term disease control. Recruitment of the trial will continue beyond the planned population of 102 patients in order to ensure the inclusion of an appropriate number of patients with squamous cell histology for a complete primary analysis of this tumour variant.

• Top-line results of a Phase II trial of NGR-hTNF in combination with doxorubicin for the treatment of relapsed small-cell lung cancer (ASCO abstract 7077). The trial enrolled 28 patients: over half of the patients showed disease control, with similar antitumour activity in terms of disease regression in both chemo-sensitive and chemo-refractory patients.

One third of patients were progression-free at six months and alive at 1-year, with prolonged clinical benefit observed also in patients heavily pre-treated with two or more prior therapies. Additionally, we observed a double survival time in patients presenting a low Neutrophil to Lymphocyte Ratio (8.4 months) as compared to patients with high ratio (4.6 months). This biological index indirectly confirms the role of the effector immune system in the NGR-hTNF mechanism of action.

• Long-term follow up data of a completed Phase II trial in malignant pleural mesothelioma (ASCO abstract 7089). In this multicentre, single-arm trial, NGR-hTNF was tested as second line therapy in 57 relapsed patients, treated with the same dose of NGR-hTNF administered either every 3 weeks or every week.

Long-term survival analysis confirms a strong advantage of the weekly over the tri-weekly administration schedule: the 2-year survival rate was three-fold higher considering the entire patient population and five-fold higher in patients who achieved disease control at the first tumour re-assessment.

In both cohorts, patients who achieved disease control at the first tumour re-assessment and continued therapy had a double median survival time with respect to patients who progressed at the first tumour re-assessment and consequently discontinued treatment (16.7 v 8.3 months).

Evaluation of the weekly schedule of NGR-hTNF for the treatment of chemo-pretreated malignant pleural mesothelioma patients is currently being investigated in a double-blind, placebo-controlled randomized Phase III trial.

Moreover, based on the long-term effect of the drug in disease control, MolMed announces the start of a randomized, placebo-controlled Phase II trial as first line maintenance treatment for patients who completed the pemetrexed-based chemotherapy.

The trial is planning to enrol 100 patients and will investigate the effects of the administration of NGR-hTNF in prolonging the benefits attained with chemotherapy; the primary endpoint of the trial is progression-free survival.

Clinical data obtained by MolMed to date demonstrate the antitumour activity of NGR-hTNF in six different types of solid tumours; these include two orphan indications as well as more widespread diseases, which altogether account for more than 1.4 million new cases each year in Europe, North America and Japan.