Retifanlimab Continues to Elicit Responses in Recurrent MSI-H or dMMR Endometrial Cancer

Retifanlimab-dlwr (Zynyz) continued to elicit responses with acceptable tolerability in patients with recurrent microsatellite instability–high (MSI-H) or mismatch repair­–deficient (dMMR) endometrial cancer, according to final findings from cohort H of the phase 1 POD1UM-101 trial (NCT03059823) presented at the 2023 ESMO Congress.¹

At a median follow-up of 26.0 months (range, 2.3-42.5), Retifanlimab elicited an objective response rate (ORR) of 51.3% (95% CI, 39.6%-63.0%), which was comprised of a complete response (CR) rate of 25.0%, a partial response (PR) rate of 26.3%, and a stable disease (SD) rate of 26.3%. Moreover, 19.7% of patients experienced disease progression; this information was missing in 2.6% of patients, as no post-baseline assessments were available. The disease control rate was 77.6% (95% CI, 66.6%-86.4%).

The median duration of response (DOR) was not yet reached (NR; 95% CI, 31.8-not evaluable [NE]), with 87.2% and 76.9% of patients experiencing a response that persisted for at least 6 months and 12 months, respectively. The median progression-free survival (PFS) was 12.2 months (95% CI, 6.0-33.4) and the median overall survival (OS) was 30.2 months (95% CI, 19.3-NE).

“In patients with pretreated, locally advanced recurrent or metastatic MSI-H/dMMR endometrial cancer, retifanlimab [given at] 500 mg every 4 weeks shows characteristic safety and tolerability for this class,” Dominique Berton-Rigaud, MD, of Service d’Oncologie Médicale, GINECO and Institut de Cancérologie de l’Ouest in Saint-Herblain, France, and colleagues, wrote in a poster on the data. “Based on results from POD1UM-101, further investigation of retifanlimab as monotherapy or in combination with other immunotherapy or targeted agents is ongoing in patients with advanced or metastatic endometrial cancer.”

POD1UM-101 included tumor-specific cohorts and tumor-agnostic flat-dose cohorts.

Those in the tumor-specific cohorts received retifanlimab at 3 mg/kg every 2 weeks; these patients had endometrial cancer (n = 29; cohort A), cervical cancer (n = 35; cohort B), soft tissue sarcoma (n = 35; cohort C), and non–small cell lung cancer (n = 35; cohort D).

Those in the tumor-agnostic cohorts included those who received the agent at 500 mg every 4 weeks (n = 15; cohort E), those who were given the agent at 750 mg every 4 weeks (n = 15; cohort F), those who received the agent at 375 mg every 3 weeks (n = 15; cohort G), those with MSI-H or dMMR endometrial cancer who received the drug at 500 mg every 4 weeks (n = 88; cohort H), and those with MSI-H or dMMR endometrial cancer in China only at 500 mg every 4 weeks (n = 21; cohort I).

To be included in cohort H, patients needed to have histologically proven, unresectable recurrent endometrial cancer that was MSI-H or dMMR per local testing who had progressed during or after 1 to 5 prior systemic therapies. Patients needed to be at least 18 years of age, measurable disease by RECIST v1.1 criteria, an ECOG performance status of 0 or 1, and acceptable liver and renal function.

If patients had symptomatic or untreated central nervous system metastases or a history of known or suspected autoimmune disease, they were excluded. They could not have previously received an immune checkpoint inhibitor or systemic corticosteroids or immunosuppressant drugs within 2 weeks before the start of study treatment.

The primary end point of the study was safety and tolerability and secondary end points included ORR, DOR, PFS, OS.

At a data cutoff date of May 17, 2023, a total of 76 patients had been given at least 1 dose of retifanlimab. Patients received a median of 11.5 infusions of the agent (range, 1-26) with a median duration of treatment of 10.0 months (range, 0.03-25.9).

The median patient age was 67 years (range, 49-88). More than half of patients were White (73.7%) and had an ECOG performance status of 1 (57.9%). Regarding tumor stage at study entry, 11.8% had locally advanced disease and 88.2% had metastatic disease. Most patients (80.3%) had visceral metastases. In terms of histology, 92.1% had endometrioid carcinoma and 2.6% had mixed carcinoma. Moreover, 85.5% of patients had MSI-H disease and 14.5% had dMMR disease. In terms of PD-L1 tumor proportion score, 72.4% had a score of less than 1% and 26.3% had a score of 1% or higher.

Most patients (96.1%) received prior systemic treatment for advanced disease with 43.4% having received at least 2 prior lines of systemic therapy for advanced disease. Additionally, 71.1% and 89.5% of patients previously received radiotherapy or underwent surgery, respectively.

Earlier data from cohort H of POD1UM-101 showed that at a median follow-up of 8.4 months (range, 1.9-28.3).² The confirmed ORR with retifanlimab was 43.4% (95% CI, 32.1%-55.3%), with a CR and PR of 14.5% and 29.9%, respectively. The SD rate was 32.9% and 21.1% experienced disease progression. The median DOR was NR and the DCR was 76.3% (95% CI, 65.2%-85.3%). The median PFS was 11.0 months (95% CI, 5.6-NE) and the median OS was NE (95% CI, 19.3-NE).

Of the 76 patients enrolled in the trial, 30.3% completed treatment and 69.7% discontinued treatment. The most common reason for discontinuation was disease progression or lack of efficacy (44.7%), followed by adverse effect (AE; 17.1%), death (3.9%), other (2.6%), or patient withdrawal (1.3%).

Treatment-emergent AEs (TEAEs) were experienced by 98.7% of patients and 82.9% experienced treatment-related TEAEs. Grade 3 or higher TEAEs were reported in half of patients and 18.4% had grade 3 or higher treatment-related TEAEs. Serious AEs occurred in 40.8% of patients; these effects were treatment related in 7.9% of patients. TEAEs of special interest were reported in 26.3% of patients. TEAEs resulted in discontinuation for 17.1% of patients; they led to interruptions for 36.8% of patients. Two patients experienced TEAEs that resulted in death; 1 had large intestinal stenosis and 1 had renal failure.

The most common treatment-related AEs occurring in at least 5% of patients included fatigue (any-grade, 18.4%; grade ≥3, 0%), diarrhea (15.8%; 1.3%), pruritus (15.8%; 0%), asthenia (14.5%; 0%), arthralgia (10.5%; 0%), rash (10.5%; 1.3%), hypothyroidism (9.2%; 0%), hyperthyroidism (7.9%; 0%), reduced appetite (6.6%; 0%), dry skin (5.3%; 0%), pruritic rash (5.3%; 0%), and vomiting (5.3%; 0%).

Potential immune-related TEAEs that were reported in at least 2 patients included skin reactions (any grade, 13.2%; grade ≥3, 1.3%), hyperthyroidism (10.5%; 0%), hypothyroidism (9.2%; 0%), nephritis (5.3%; 5.3%), pneumonitis (5.3%; 1.3%), hepatitis (3.9%; 2.6%), and Guillain-Barre Syndrome: polyneuropathy (2.6%; 0%).

The safety and efficacy of retifanlimab monotherapy or paired with other agents in patients with advanced or metastatic endometrial cancer who have progressed during or following platinum-based chemotherapy is under evaluation as part of the ongoing phase 2 POD1UM-204 trial (NCT04463771).³

Editor’s Note: Dr Berton-Rigaud did not have anything to disclose.

References

1. Berton-Rigaud D, Pautier P, Lorusso D, et al. 775P retifanlimab in patients with recurrent microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) endometrial cancer: first results from the POD1UM-101 study (cohort H). Ann Oncol. 2023;34(suppl 2):S517. doi:10.1016/j.annonc.2023.09.1934
2. Berton D, Pautier P, Lorusso D, et al. Retifanlimab (INCMGA00012) in patients with recurrent MSI-H or dMMR endometrial cancer: results from the PODIUM-101 study. Presented at: 2021 SITC Annual Meeting; November 10-14, 2021; Washington DC. Abstract 956.
3. Safety and efficacy of retifanlimab (INCMGA00012) alone or in combination with other therapies in participants with advanced or metastatic endometrial cancer who have progressed on or after platinum-based chemotherapy (POD1UM-204). ClinicalTrials.gov. Update October 26, 2023. Accessed November 27, 2023. https://clinicaltrials.gov/study/NCT04463771