AUSTRALIA — Australia’s Immutep has extended a Clinical Trial Collaboration and Supply Agreement with Merck KGaA and Pfizer for a new Phase I clinical study in patients with urothelial cancer, called INSIGHT-005.
INSIGHT-005 will be an investigator-initiated explorative, open-label study evaluating the safety and efficacy of Immutep’s lead product candidate, efti, in combination with avelumab (BAVENCIO) in up to 30 patients with metastatic urothelial cancer.
The study will take place in Germany. The first patient is expected to be enrolled and dosed in H1 of calendar year 2023, after completing the necessary ethics and regulatory steps.
In 2018, both Merck KGaA and Pfizer became collaboration partners of Immutep to facilitate the evaluation of efti in combination with avelumab.
Urothelial cancer is a type of cancer in the bladder or urinary tract. In the US alone, it is estimated there will be 81,180 new cases of bladder cancer in 2022 and an estimated 17,100 people will die of this disease.
Avelumab is a checkpoint inhibitor that works by targeting and blocking a protein called programmed death-ligand 1 (PD-L1) on the surface of certain immune cells, activating the cells to find and kill cancer cells.
It is approved in more than 60 countries around the world as a monotherapy for first-line maintenance treatment for adult patients with advanced urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy.
Immune checkpoint proteins, especially PD-L1 and PD-1, play a crucial role in controlling the intensity and duration of the immune response, thus preventing the development of autoimmunity.
Similarly, these proteins play a vital role in enabling cancer cells to escape immunity, proliferate and progress.
Avelumab is co-developed and co-commercialized by Merck KGaA, Darmstadt, Germany, and Pfizer.
Under the Agreement, Immutep and Merck KGaA, Darmstadt, Germany will jointly fund the INSIGHT-005 study.
It will be conducted by the Institute of Clinical Cancer Research, Krankenhaus Nordwest (IKF) as part of the investigator-initiated INSIGHT platform for studies investigating efti in different combination treatments and routes of administration.
INSIGHT consists of 5 different arms from stratums A to E (INSIGHT-005 is Stratum E).
Roche anti-PD-L1 antibody fails to meet primary endpoint
Still, on renal oncology front, Roche has voluntarily withdrawn atezolizumab’s indication in the United States for the treatment of adults with locally advanced or metastatic urothelial carcinoma.
The trial failed to meet one of its co-primary endpoints of improved overall survival (OS) with atezolizumab-chemotherapy vs. chemotherapy alone.
The indication applied to use of atezolizumab (Tecentriq, Genentech) — an anti-PD-L1 antibody — by patients who are ineligible for cisplatin-containing chemotherapy and whose tumors express PD-L1, or those ineligible for platinum-containing chemotherapy regardless of PD-L1 status.
The decision was made in consultation with the FDA, which had previously granted atezolizumab accelerated approval for this indication.
The randomized phase 3 IMvigor trial evaluated the addition of atezolizumab to platinum-based chemotherapy as first-line therapy for treatment-naive advanced bladder cancer as part of the post-marketing requirements to convert the accelerated approval to regular approval.
Roche’s decision does not affect other approved indications for atezolizumab in the United States. The agent is approved for certain patients with non-small cell lung cancer, liver cancer, or melanoma.