Results from a Phase 1 extension study further confirmed the potential of ADI-PEG 20 to enhance the effectiveness of two chemotherapies — Platinol (cisplatin) and Alimta (pemetrexed) — commonly used to treat ASS1-deficient malignant pleural mesothelioma (MPM).
A Phase 2/3 trial in these patients is now beginning in the U.S., Europe and elsewhere.
Phase 1 extension results will be presented in a poster, “Expansion study of ADI-PEG 20, pemetrexed and cisplatin in patients with ASS1-deficient malignant pleural mesothelioma (TRAP)” during the 2017 American Society of Clinical Oncology (ASCO) annual meeting, to be held June 2-6 in Chicago.
Previous studies have demonstrated that an amino acid called arginine is critical for MPM progression. Many types of cancers, including MPM, lack the expression of argininosuccinate synthetase 1, or ASS1, which is the enzyme responsible for the production of arginine. This means that these cancers are entirely dependent on an external source of arginine to survive.
ADI-PEG 20 (pegylated arginine deiminase) is an enzyme that degrades arginine. When given to ASS1-deficient MPM patients, this investigational drug is expected to destroy external arginine in order to kill MPM cancer cells with no negative effect on the patient’s healthy cells.
The extension study of the Phase 1 trial (NCT02029690), called TRAP, tested the efficacy of ADI-PEG 20 added to first-line Platinol and Alimta chemotherapy for ASS1-deficient MPM. The study included a total of 31 patients with different subtypes of ASS1-deficient MPM: 11 epithelioid, 10 biphasic, and 10 sarcomatoid MPM.
The treatment induced a disease control rate of 93.5%, with a partial response rate of 35.5%. In addition, the median progression-free survival rate was 5.6 months, and the median overall survival was 10.1 months.
Ten patients receiving ADI-PEG 20 plus chemotherapy experienced moderate to severe treatment-related adverse events. The most common was lowered levels of a subtype of immune cells called neutrophils, which increases the risk of infections.
These positive results support further development of this therapy for ASS1-deficient MPM, including in non-epithelioid forms of the disease.
Polaris Group, the therapy’s developer, is now sponsoring a multicenter, placebo-controlled Phase 2/3 trial, called ATOMIC (NCT02709512), to assess the benefits of adding ADI-PEG 20 to standard chemotherapy Platinol and Alimta, and possibly Paraplatin (carboplatin). (This trial is also the subject of an ASCO presentation.)
The trial, currently enrolling participants across the U.S. and Asia (enrollment in Europe and Australia is almost complete), is expected to include up to 386 patients with non-epithelioid MPM. The study’s primary endpoint for Phase 2 is overall response rate; in Phase 3, its primary objective is measures of overall survival.