一项II期多队列研究，评估lorigerlimab（PD-1 x CTLA-4）在晚期实体瘤参与者中的疗效

Background: Platinum-resistant ovarian cancer (PROC) and clear cell gynecologic cancer (CCGC) are associated with poor prognoses and have limited effective treatment options. PROC has a recurrence rate of approximately 70%, while CCGC, a rare histologic subtype, demonstrates resistance to most standard therapies. These unmet clinical needs underscore the importance of developing novel therapeutics to improve patient outcomes. Immune checkpoint inhibitors have shown promising preliminary antitumor activity in PROC and CCGC, although they are not currently approved for either indication. Lorigerlimab is an investigational bispecific (PD-1 x CTLA-4), tetravalent DART ® molecule. It is engineered to enhance CTLA-4 blockade in a PD-1-binding-dependent manner, intended to improve activity in the tumor microenvironment while minimizing off-tumor toxicity. Preclinical and early-phase clinical data support lorigerlimab immunomodulatory activity and tolerability. This study investigates the efficacy and safety of lorigerlimab monotherapy in patients with PROC and CCGC. Methods: This open-label, multicohort, multi-institutional, phase 2 study (NCT06730347) evaluates lorigerlimab monotherapy in participants with PROC (cohort A) or CCGC (cohort B). Cohort A utilizes a Simon's two-stage design to enroll up to 40 participants and cohort B will enroll up to 20 participants. Participants receive lorigerlimab intravenously every 3 weeks for up to 35 cycles or until disease progression, unacceptable toxicity, or withdrawal. The primary objective is to evaluate the antitumor activity as measured by objective tumor response. Secondary objectives include characterization of safety, tolerability, and evaluation of efficacy by duration of response, disease control rate, progression-free survival, and change in tumor size from baseline. Eligible participants must have persistent or recurrent high-grade serous ovarian carcinoma or clear cell gynecologic cancers with at least 50% clear cell histomorphology. Participants with PROC must have received at least one and up to three prior lines of systemic therapy, which may include prior bevacizumab. Individuals with a germline or somatic BRCA mutation must have received PARP inhibitor therapy. Participants with CCGC must have received at least one prior line. All participants must have good functional status, measurable disease, adequate organ function, and no contraindications to immunotherapy. Individuals with primary platinum-refractory disease are excluded. Prior use of checkpoint inhibitor therapy is permitted for participants with clear cell endometrial or clear cell cervical cancer. Tumor assessments occur every 9 weeks for the first 54 weeks, then every 12 weeks until treatment discontinuation. Enrollment commenced in May 2025 and is ongoing.