Transgene Completes Enrollment for Phase 2 Trial of Triple Combo NSCLC Therapy

Transgene has completed patient enrollment for its Phase 2 trial evaluating the cancer vaccine TG4010 in combination with Opdivo (nivolumab) and chemotherapy as a first-line treatment for advanced non-squamous non-small cell lung cancer (NSCLC) with low or no expression of PD-L1.

The first results regarding the trial’s primary endpoint — the rate of response to the combo measured in at least 35 patients — will be reported in the fourth quarter of the year, Transgene announced in a press release.

TG4010 is a type of immunotherapy designed as a cancer vaccine, meaning it is formulated to stimulate a type of immune cell, termed a T cell, to recognize and attack tumor cells. For that, TG4010 contains MUC1 — a protein highly abundant in non-small cell lung cancer (NSCLC) and other tumors — and the cytokine interleukin-2 (IL2) — a potent T-cell growth factor.

The MUC1 protein is also present at the surface of certain normal cells, but in tumors MUC1 carries many sugar modifications that distinguish it from that of normal cells. This makes MUC1 an attractive target for cancer immunotherapy.

TG4010 is based on a modified version of the Vaccinia virus and is directed to stimulate an immune response against MUC1-expressing tumors, such as NSCLC. Its mechanism of action and excellent safety profile, Transgene says, make TG4010 a good candidate to combine with other therapies, including chemotherapy and immune checkpoint inhibitors, such as anti-PD-1 therapy Opdivo, marketed by Bristol-Myers Squibb.

In a prior Phase 2a study (NCT01383148), a combination of TG4010 with chemotherapy was seen to prolong life without cancer progression in patients with advanced NSCLC.

Transgene is now running a Phase 2 trial (NCT03353675) to evaluate the efficacy and safety of TG4010 plus Opdivo and standard platinum doublet chemotherapy for patients with advanced non-squamous NSCLC, whose tumors express little to no PD-L1 and thus are likely resistant to immune checkpoint inhibitors like Opdivo.

The trial is being conducted by Transgene in collaboration with Bristol-Myers Squibb, which is supplying Opdivo and has just completed enrollment at sites in the United States and Europe.

The trial’s primary outcome measure is overall objective response rate (ORR) — the proportion of patients whose tumors shrink at least 30% (partial response) or become undetectable.

Other objectives are to assess the safety and tolerability of the regimen as well as other efficacy and immunological parameters. For more information about the trial, go to clinicaltrials.gov.

“We are looking forward to reporting the first efficacy data of our active immunotherapy TG4010, with nivolumab and chemotherapy as a first-line treatment of advanced lung cancer for patients whose tumors express low or undetectable levels of PD-L1,” Maud Brandely, chief medical officer of Transgene, said in the release.

“Today anti-PD-1 therapy is relatively less effective in this large subset of NSCLC patients. With this triple combination regimen, we aim to significantly improve treatment outcomes in this major oncology indication,” Brandely said.

Lung cancer is one of the most common cancers worldwide, with an estimated 2.1 million new cases each year. Approximately 80% to 85% of these tumors are non-small cell lung cancers (NSCLC).

Advanced stages of lung cancer remain among the malignancies with the worst prognoses — a five-year survival rate for advanced NSCLC of less than 5% — underlining the high unmet need for therapies.