First Mesothelioma Patient Dosed in Phase 1 Trial of Curis’ CA-170

The Phase 1 trial evaluating Curis‘ investigational immunotherapy CA-170 for advanced cancers has dosed its first mesothelioma patient, the company announced.

The trial (NCT02812875), currently enrolling participants, will test the therapy in adults with advanced solid tumors, including mesothelioma, or lymphomas who failed to respond to standard therapies.

CA-170 is an oral small molecule that selectively inhibits PD-L1 and VISTA, both of which work as negative regulators of immune activation. Cancer cells produce PD-L1 and VISTA to suppress the function of T cells — the “soldiers” of the immune system driving anti-cancer responses.

Over 90% of mesothelioma cells are positive for VISTA; CA-170 is currently the only VISTA inhibitor in clinical testing.

The ongoing Phase 1 trial, aiming to enroll 300 patients across the U.S., U.K., Korea, and Spain, will be conducted in two parts. First, patients will receive escalating doses of CA-170, administered orally once or twice daily, to determine the safest and most effective dose for further testing.

Then, a dose expansion phase will test the selected dose in patients whose tumors are known to respond to anti-PD-1 or anti-PD-L1 inhibitors, or whose tumors are positive for PD-L1 or VISTA.

Mesothelioma patients will have their own dedicated group, and will receive CA-170 at two dose levels.

The trial’s primary goal is to determine the safety and tolerability of CA-170, the maximum tolerated dose and the recommended Phase 2 dose. Additional (secondary) endpoints include pharmacokinetics (the compound’s absorption, distribution, metabolism, and excretion in the body) and anti-tumor activity.

Previous studies in animals showed that CA-170 can promote proliferation and activation of a subset of T cells whose activity is impaired by PD-L1 or VISTA. In multiple animal cancer models, CA-170’s anti-tumor activity was similar to that of antibodies inhibiting PD-1 or VISTA. Preclinical data also showed CA-170 was safe at multiple dose levels.

Mesothelioma is an aggressive cancer that occurs in the thin layer of tissue that covers most of our internal organs. There is currently no disease-modifying therapy that effectively increases the survival of these patients.

“We are pleased to announce that the CA-170 study has begun dosing patients ahead of schedule,” James Dentzer, president and CEO of Curis, said in a press release.

“On last quarter’s earnings call, we outlined the reorganization of company resources to strengthen focus on clinical execution. … We reiterate our confidence in our expectation to report initial efficacy data in this study in the second half of 2019,” Dentzer said.