Endometrial cancer tumors shrank by more than 70%! Retifanlimab is expected to become a new treatment standard
Treatment options for patients with recurrent or metastatic endometrial cancer are limited, and the prognosis is poor, with a 5-year survival rate of approximately 17.0%. About 25.0% of endometrial cancers are MSI-H or dMMR. Because these tumors are characterized by abnormal DNA repair and are associated with numerous neoantigens, PD-1 immunotherapy is a viable option. Data from the Phase 1 POD1UM-101 trial, presented at the 2021 SITC Annual Meeting, showed that the novel immunotherapy drug Retifanlimab demonstrated encouraging antitumor activity and good tolerability in patients with recurrent microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) endometrial cancer.
Retifanlimab drug introduction
Drug name: Retifanlimab
Other drug names: INCMGA 0012
Developer: Incyte
Retifanlimab is an investigational humanized immunoglobulin G4 monoclonal antibody against PD-1. PD-1 is an inhibitory receptor, expressed on some tumor cells, which leads to the downregulation of the immune system by reducing the activity of T cells. Anti-PD-1 monoclonal antibodies block the PD-1 receptor, so T cells are no longer suppressed, thereby activating the immune response against the tumor.
Retifanlimab International Research Data
The POD1UM-101 trial (NCT03059823) recruited patients with at least 18 years old, histologically confirmed, non-resectable recurrent endometrial cancer. According to local tests, these patients were MSI-H or dMMR. According to the RECIST v1.1 standard, the patient must have a measurable disease and have progressed during or after 1 to 5 previous systematic treatments. In addition, the patient's ECOG performance is 0 or 1, and there are sufficient laboratory parameters for liver and kidney. Tumor specimens need to be collected for retrospective central confirmation of MSI-H/dMMR status and PD-L1 expression testing.
Among the 76 selected patients, the median age was 67 years old (range 49-88); most were white (73.7%), and the ECOG performance status was 1 (59.2%). In addition, most patients have metastatic disease (88.2%), visceral metastasis (80.3%), and histology is endometrial cancer (92.1%). In addition, 72.4% of patients had PD-L1 expression less than 1%.
It is worth noting that 98.7% of patients have received systematic treatment for any disease before, and 96.1% of patients have received systematic treatment for advanced diseases before. In addition, 65.8% of patients had received 1 treatment before, 22.4% of patients had received 2 treatments before, and 7.9% of patients had received 3 or more treatments before. In addition, 71.1% of patients had previously received radiotherapy and 89.5% had previously undergone surgery.
Patients selected for group H of the study received Retifanlimab at a dose of 500 mg every 4 weeks. The patient will receive 2 years of follow-up. The main endpoints of the study were safety and tolerability, and secondary endpoints included ORR, DOR, PFS, and OS. In this analysis, the researchers shared the results of the safety and clinical activity of Retifanlimab in patients with MSI-H or dMMR recurrent endometrial cancer, which is group H of the POD1UM-101 study.
As of the data cutoff on July 6, 2021, 76 patients had received at least one dose of Retifanlimab, of whom 2 (2.6%) completed treatment and 30 (39.5%) were still on treatment. 44 patients (57.9%) discontinued treatment, primarily due to radiation-induced disease progression (38.2%) and adverse events (AEs; 11.8%). Other reasons for discontinuation included clinical progression (2.6%), death (2.6%), patient withdrawal (1.3%), or other reasons (1.3%). Patients received 0 infusions of 500 mg Retifanlimab every 4 weeks (range 1–26 times), with a median treatment duration of 7.4 months (range 0.03–23.0). 64% of patients (n = 14/22) achieved a confirmed partial response (PR) with Retifanlimab, with tumor volume shrinking by more than 70%. 29 of the 33 responders are still on treatment.
At a median follow-up of 8.4 months (range 1.9–28.3), the objective response rate (ORR) confirmed by RECIST v1.1 criteria was 43.4% (n = 33/76; 95% CI, 32.1%–55.3%); this included 11 complete responses (14.5%) and 22 partial responses (PRs; 28.9%). Furthermore, 32.9% (n = 25) of patients achieved disease stability, and 21.1% (n = 16) experienced disease progression.
The median time to response (DOR) for retifanlimab has not been reached; 75.8% (n = 25) of patients experienced a DOR of 6 months or longer. The disease control rate was 76.3% (95% CI, 65.2%–85.3%). Furthermore, the median progression-free survival (PFS) with this drug was 11.0 months (95% CI, 5.6–non-evaluable [NE]), and the median overall survival (OS) was NE (95% CI, 19.3–NE). In addition, 6 patients had a sustained response after discontinuation of treatment. In these patients, the DOR from treatment discontinuation varied from 3.0 to 24.9 months for each independent review committee.
Regarding safety, 74 patients (97.4%) experienced at least one treatment-related adverse event (TRAE), and 11 patients (14.5%) reported a grade 3 or higher TRAE. Four patients (5.3%) reported immune-related TRAEs leading to study drug discontinuation, including autoimmune hepatitis (n = 1), hepatitis (n = 1), myositis (n = 1), and polyrheumatoid arthritis (n = 1). The most common TRAEs of any grade were fatigue (18.4%), pruritus (15.8%), diarrhea (14.5%), wheezing (14.5%), rash (10.5%), arthralgia (9.2%), hypothyroidism (9.2%), hyperthyroidism (7.9%), decreased appetite (6.6%), and rash/pruritus (5.3%). The most common grade 3 or higher TRAEs were diarrhea (1.3%) and rash (1.3%).
Reminder: Preliminary research data show that Retifanlimab has good activity in patients with recurrent MSI-H or dMMR endometrial cancer. It is hoped that the therapy will obtain better trial results, be approved as soon as possible and be used clinically for the benefit of more cancer patients.
