A phase II study of retifanlimab (INCMGA00012) in patients with squamous carcinoma of the anal canal who have progressed following platinum-based chemotherapy (POD1UM-202)

S, Rao; Anandappa, Gayathri; Capdevila, Jaume; Dahan, Laétitia; Evesque, Ludovic; Kim, Stéfano; Saunders, Mark; Gilbert, Duncan C.; Jensen, Lars Henrik; Samalin, Emmanuelle; Spindler, K. G.; Tamberi, Stefano; Demols, A.; Guren, Marianne G.; Arnold, Dirk; Fakih, Marwan; Kayyal, T; Cornfeld, Mark; Tian, Chuan; Catlett, M.; Smith, Michael; Spano, J. P.

doi:10.1016/j.esmoop.2022.100529

Cited by 36 publications

(24 citation statements)

References 50 publications

(78 reference statements)

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“…For patients with unresectable and/or metastatic squamous cell carcinoma of the anal canal, treatment with immune checkpoint blockade therapies has demonstrated modest clinical activity, with response rates ranging between 10 and 24% [ 19 , 20 , 21 , 33 , 34 ]. In small post hoc correlative analyses for these clinical trials, the increased expression of PD-L1 has been associated with a greater likelihood for response to therapy [ 19 , 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, therapies targeting these mutations have historically not been utilized as a treatment for anal cancer. To date, immune checkpoint blockade agents have demonstrated anti-tumor efficacy for patients with metastatic anal cancer [ 19 , 20 , 21 ]. In these series, translational analyses of small subsets of patients have suggested that PD-L1 expression has been linked to improved treatment efficacy and survival outcomes.…”

Section: Introductionmentioning

confidence: 99%

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Differential Spatial Gene and Protein Expression Associated with Recurrence Following Chemoradiation for Localized Anal Squamous Cell Cancer

Hernandez

Das

Holliday

et al. 2023

Cancers

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The identification of transcriptomic and protein biomarkers prognosticating recurrence risk after chemoradiation of localized squamous cell carcinoma of the anus (SCCA) has been limited by a lack of available fresh tissue at initial presentation. We analyzed archival FFPE SCCA specimens from pretreatment biopsies prior to chemoradiation for protein and RNA biomarkers from patients with localized SCCA who recurred (N = 23) and who did not recur (N = 25). Tumor cells and the tumor microenvironment (TME) were analyzed separately to identify biomarkers with significantly different expression between the recurrent and non-recurrent groups. Recurrent patients had higher mean protein expression of FoxP3, MAPK-activation markers (BRAF, p38-MAPK) and PI3K/Akt activation (phospho-Akt) within the tumor regions. The TME was characterized by the higher protein expression of immune checkpoint biomarkers such as PD-1, OX40L and LAG3. For patients with recurrent SCCA, the higher mean protein expression of fibronectin was observed in the tumor and TME compartments. No significant differences in RNA expression were observed. The higher baseline expression of immune checkpoint biomarkers, together with markers of MAPK and PI3K/Akt signaling, are associated with recurrence following chemoradiation for patients with localized SCCA. These data provide a rationale towards the application of immune-based therapeutic strategies to improve curative-intent outcomes beyond conventional therapies for patients with SCCA.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Differential Spatial Gene and Protein Expression Associated with Recurrence Following Chemoradiation for Localized Anal Squamous Cell Cancer

Hernandez

Das

Holliday

et al. 2023

Cancers

View full text Add to dashboard Cite

show abstract

“…and were also evaluated in SCCA, as well as other anti-PD1 antibodies (nivolumab, retifanlimab) (51), and showed a promising result in a subgroup of patients (52)(53)(54).…”

Section: Discussionmentioning

confidence: 99%

Prognostic role of HPV integration status and molecular profile in advanced anal carcinoma: An ancillary study to the epitopes-HPV02 trial

et al. 2022

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Squamous Cell Carcinoma of the Anal canal (SCCA) is a rare disease associated with a Human Papillomavirus (HPV) infection in most cases, predominantly the HPV16 genotype. About 15% of SCCA are diagnosed in metastatic stage and some will relapse after initial chemoradiotherapy (CRT). Treatment of patients by Docetaxel, Cisplatin and 5-fluorouracil (DCF) has been recently shown to improve their complete remission and progression-free survival. The aim of this retrospective study was to explore the impact of HPV infection, HPV DNA integration, TERT promoter mutational status and somatic mutations of oncogenes on both progression-free (PFS) and overall survivals (OS) of patients treated by DCF. Samples obtained from 49 patients included in the Epitopes-HPV02 clinical trial, diagnosed with metastatic or non-resectable local recurrent SCCA treated by DCF, were used for analyses. Median PFS and OS were not associated with HPV status. Patients with episomal HPV had an improved PFS compared with SCCA patients with integrated HPV genome (p=0.07). TERT promoter mutations were rarely observed and did not specifically distribute in a subset of SCCA and did not impact DCF efficacy. Among the 42 genes investigated, few gene alterations were observed, and were in majority amplifications (68.4%), but none were significantly correlated to PFS. As no biomarker is significantly associated with patients’ survival, it prompts us to include every patient failing CRT or with metastatic disease in DCF strategy.

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“…). Retifanlimab has already demonstrated its safety and efficacy in SCCA patients in PODIUM 202 phase II trial in chemorefractory patients ( 5 ). In PODIUM 303/InterAACT 2, approximately 300 patients with inoperable locally recurrent or metastatic SCCA not previously treated with systemic chemotherapy will be included.…”

mentioning

confidence: 99%

“…PODIUM 303/InterAACT 2 study presented here is a phase III international randomized double-blind study of retifanlimab (anti-PD1 inhibitor) or placebo plus carboplatin and paclitaxel (Rao et al). Retifanlimab has already demonstrated its safety and efficacy in SCCA patients in PODIUM 202 phase II trial in chemorefractory patients (5). In PODIUM 303/InterAACT 2, approximately 300 patients with inoperable locally recurrent or metastatic SCCA not previously treated with systemic chemotherapy will be included.…”

mentioning

confidence: 99%

Editorial: New understandings and research in anal squamous cell carcinoma

2023

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A phase II study of retifanlimab (INCMGA00012) in patients with squamous carcinoma of the anal canal who have progressed following platinum-based chemotherapy (POD1UM-202)

Cited by 36 publications

References 50 publications

Differential Spatial Gene and Protein Expression Associated with Recurrence Following Chemoradiation for Localized Anal Squamous Cell Cancer

Differential Spatial Gene and Protein Expression Associated with Recurrence Following Chemoradiation for Localized Anal Squamous Cell Cancer

Prognostic role of HPV integration status and molecular profile in advanced anal carcinoma: An ancillary study to the epitopes-HPV02 trial

Editorial: New understandings and research in anal squamous cell carcinoma

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