CytomX Therapeutics has initiated a Phase 2 clinical trial to test a combination of its probody CX-072 — a type of engineered antibody — with Yervoy (ipilimumab) for treating people with relapsed or refractory melanoma.
The investigational probody CX-072 and Yervoy, developed by Bristol-Myers Squibb, are two immune checkpoint inhibitors designed to boost the body’s anti-tumor response. They target proteins involved in the mechanisms used by cancer cells to evade immune system attack. CX-072 targets the PD-L1 protein on cancer cells, and Yervoy targets the CTLA-4 protein on T-cells, which are immune cells involved in the fight against cancer.
Unlike approved immune checkpoint inhibitors, the probody is a kind of monoclonal antibody bound to a masking peptide, which is only cleaved in the presence of tumor-associated proteases —proteins that break down other proteins. This makes sure that CX-072 is only active in the presence of cancer cells, minimizing damage and toxicity to healthy cells.
The combination showed promise in a prior Phase 1 trial (NCT03013491) for advanced solid tumors. In that study, 37% of participants had some sort of benefit — stable disease or a response — and 19% responded to treatment. The responses were durable, lasting a median of 14.6 months, the results showed.
That trial tested multiple doses of both Yervoy and CX-072, and determined that the optimal combination dose was 3 mg/kg of Yervoy and 800 mg of CX-072. This combination was well-tolerated with no new safety issues.
The newly initiated Phase 2 trial — PROCLAIM-CX-072-002 (NCT03993379) — is now testing this combination at the recommended dose in people with inoperable or metastatic melanoma who failed prior treatment with an immune checkpoint inhibitor targeting the PD-1 or PD-L1 molecules.
Participants will receive both treatments every three weeks for four cycles, and continue on CX-072 alone every two weeks until their disease progresses or signs of toxicity are evident.
The trial’s primary goal is overall response rate (ORR), or the proportion of patients achieving a significant reduction of tumor volume. Secondary measures include safety and other efficacy assessments.
Designed to include approximately 40 patients in the first stage, the trial will enroll additional participants pending the initial results. More information on enrollment is available here. Data from the first part is expected in 2020.
“The initiation of this first Phase 2 study for CX-072 marks the ongoing advancement of our innovative pipeline of Probody therapeutics and reflects our vision for this novel checkpoint inhibitor to become a differentiated centerpiece of combination therapies in multiple cancer types,” Sean McCarthy, PhD, president, CEO, and chairman of CytomX Therapeutics, said in a press release.
“This exciting study leverages our unique technology platform to enable a more powerful combination therapy directed against the two best validated pathways in immuno-oncology and could represent a significant advance in outcomes for these patients who have few treatment options,” said Amy Peterson, MD, chief development officer of CytomX Therapeutics.