A Phase 2 Multicohort Study to Evaluate Lorigerlimab in Participants With Advanced Solid Tumors

Overview

Lorigerlimab (MGD019; AEX-1344) is an investigational cancer immunotherapy with human trial results. The most detailed peer-reviewed report is a phase 1 study in advanced solid tumors; phase 2 testing has also produced preliminary results. These findings do not yet establish a clinical benefit over existing treatments. (ascopubs.org)

Mechanism of action

Lorigerlimab is a bispecific antibody designed to block two immune checkpoints, PD-1 and CTLA-4. Its design favors CTLA-4 blockade on T cells expressing both targets, while maintaining PD-1 blockade. (ascopubs.org)

Efficacy

In the phase 1 study, 162 patients received lorigerlimab. Among patients with measurable disease in four expansion cohorts, objective responses occurred in 9/36 (25%) with metastatic castration-resistant prostate cancer, 5/42 (11.9%) with melanoma, 3/14 (21.4%) with non-small-cell lung cancer, and 1/20 (5%) with microsatellite-stable colorectal cancer. A prostate-specific antigen decline of at least 50% occurred in 12/42 (28.6%) prostate-cancer patients. The study had no control arm, and the cohorts were small. (ascopubs.org)

In an ongoing phase 2 study, the company reported confirmed partial responses in 4/16 (25%) evaluable patients with clear-cell gynecologic cancer as of May 7, 2026. These results are preliminary and company-reported. Separately, the company said an interim analysis of a randomized phase 2 prostate-cancer trial indicated that its combination with docetaxel and prednisone would not meet the trial’s radiographic progression-free-survival goal; it ended development in that setting. (sec.gov)

Safety

In phase 1, treatment-related adverse events occurred in 139/162 patients (85.8%); 36.4% had grade 3 or higher treatment-related events, and 24.7% discontinued lorigerlimab because of an adverse event. In the preliminary clear-cell gynecologic-cancer cohort, 8/17 (47%) had grade 3 or higher treatment-related events and 2/17 (12%) discontinued because of adverse events; no treatment-related deaths were reported in that cohort. (ascopubs.org)

Further reading

• Peer-reviewed phase 1 study, JCO Oncology Advances (2026). (ascopubs.org)
• Preliminary phase 2 gynecologic-cancer results (company filing, 2026). (sec.gov)

Last updated: Sep 2026

Inclusion Criteria:

* Histologically confirmed high-grade serous epithelial ovarian cancer, including primary peritoneal, or fallopian tube cancer, resistant to platinum based chemotherapy. OR

* Histologically confirmed clear cell ovarian (including primary peritoneal and fallopian tube), endometrial, vaginal, vulval, or cervical cancer.

* Persistent or recurrent disease with documented disease progression.

* Participants with PROC must have received at least 1 but not more than 3 prior lines of therapy for PROC.

* Participants with CCGC must have received at least 1 prior line of therapy for CCGC.

* Participants with a known breast cancer (BRCA) mutation (germline or somatic) must have received a a Poly ADP-ribose polymerase (PARP) inhibitor, if locally approved and available, and experienced disease progression or intolerance on the PARP inhibitor.

* Participants must have at least one lesion that meets the definition of measurable disease by RECIST v1.1.

* Participants must have an available archival or formalin-fixed paraffin-embedded tumor tissue, or be willing to undergo a biopsy procedure to obtain a fresh tumor sample.

* Participants have acceptable physical condition and laboratory values.

* Participants of childbearing potential must agree to use highly effective methods of birth control.

* Participants must not be pregnant, planning to be pregnant, or breastfeeding.

Exclusion Criteria:

* Any underlying medical or psychiatric condition impairing participant's ability to receive, tolerate, or comply with the planned treatment or study procedures.

* Primary platinum-refractory disease, defined as disease that did not respond to (CR or PR) or has progressed within 3 months of the last dose of first-line platinum- containing chemotherapy.

* Prior treatment with a checkpoint inhibitor (e.g., anti-PD-1/PD-L1, anti-PD-L2, anti-CTLA-4).

* Active brain metastases or leptomeningeal metastases.

* Prior stem cell, tissue, or solid organ transplant.

* Another hematologic or solid tumor ≥ stage 1 malignancy that completed surgery, last dose of radiotherapy, or last dose of systemic anti-cancer therapy ≤ 3 years from first dose of study treatment. Participants with another tumor that has a negligible risk for metastasis or death such as, adequately controlled basal-cell carcinoma or squamous-cell carcinoma of the skin, or carcinoma in situ of the cervix or breast are eligible.