Dostarlimab

證據等級: L5

預測適應症: 10 個

Dostarlimab: From Endometrial Cancer (dMMR/MSI-H) to Cervical Adenofibroma

One-Sentence Summary

Dostarlimab (Jemperli®) is an anti-PD-1 immune checkpoint inhibitor approved internationally — including by the FDA and Health Canada — for mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) endometrial cancer and other solid tumours. The TxGNN model predicts it may be effective for Cervical Adenofibroma, yet with 0 clinical trials and 0 publications directly supporting this direction, current evidence rests entirely on model prediction — and the mechanistic rationale is considered weak given the benign nature of this tumour.

Quick Overview

Item	Content
Original Indication	dMMR/MSI-H Endometrial Cancer (international approvals; not registered in Canada per this dataset)
Predicted New Indication	Cervical Adenofibroma
TxGNN Prediction Score	50.00%
Evidence Level	L5
Canada Market Status	✗ Not Marketed
Number of DINs	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Detailed mechanism of action data was not available in this Evidence Pack. Based on known pharmacological information, Dostarlimab is a humanised anti-PD-1 monoclonal antibody that blocks the binding of PD-1 to its ligands PD-L1 and PD-L2. This blockade restores the cytotoxic T-cell response against tumour cells that have upregulated PD-L1 as an immune evasion mechanism. Its established efficacy is concentrated in tumours with high tumour mutational burden (TMB), dMMR, or MSI-H features — all markers of heightened immunogenicity.

Cervical adenofibroma is a rare benign mixed epithelial–stromal tumour of the uterine cervix. Unlike the dMMR/MSI-H malignancies for which PD-1 blockade is indicated, benign tumours characteristically lack the immunogenic signals — including neoantigens from somatic mutations and PD-L1 upregulation — that are prerequisite for checkpoint inhibitor efficacy. There is no published evidence linking the PD-1/PD-L1 axis to the pathogenesis of cervical adenofibroma.

The TxGNN prediction most likely reflects topographic proximity in the knowledge graph (gynaecological domain overlap with the known endometrial cancer indication) rather than a genuine mechanistic connection. At present, the scientific rationale for applying Dostarlimab to cervical adenofibroma is considered insufficient to support further evaluation.

Clinical Trial Evidence

Currently no related clinical trials registered.

Literature Evidence

Currently no related literature available.

Canada Market Information

Dostarlimab is not currently registered in Canada according to this dataset (0 DINs, market status: not marketed). No product-level authorisation data is available.

Note: Dostarlimab (Jemperli®) has received regulatory approvals from the FDA (2021), EMA (2021), and Health Canada for dMMR/MSI-H endometrial carcinoma. A dataset refresh from the Health Canada Drug Product Database may be required to capture current Canadian DIN registration status.

Cytotoxicity

Item	Content
Cytotoxicity Classification	Immunotherapy — Anti-PD-1 monoclonal antibody (immune checkpoint inhibitor)
Myelosuppression Risk	Low (immune-mediated cytopenias are uncommon but reported as irAEs; unlike conventional cytotoxics, direct myelosuppression is not a primary toxicity)
Emetogenicity Classification	Minimal
Monitoring Items	Liver function (ALT, AST, bilirubin), thyroid function (TSH, free T4), adrenal/pituitary function, CBC with differential, renal function (creatinine), blood glucose, and clinical surveillance for immune-related adverse events (irAEs) at each infusion cycle
Handling Protection	Monoclonal antibody preparation — standard aseptic compounding applies; conventional cytotoxic closed-system handling is generally not required; follow institutional biosafety and biohazard protocols

Safety Considerations

Please refer to the package insert for safety information. Key warnings, contraindications, and drug interaction data were not available in this Evidence Pack.

Class-specific considerations for PD-1 checkpoint inhibitors: Dostarlimab carries well-characterised immune-related adverse event (irAE) risks, including immune-mediated pneumonitis, hepatitis, colitis, endocrinopathies (hypothyroidism, hypophysitis, adrenal insufficiency), nephritis, and dermatitis. Several predicted indications in this report (e.g., PBC/PSC–autoimmune hepatitis overlap syndrome, LAMA5-related multisystemic syndrome) represent populations where PD-1 blockade could precipitate or severely worsen pre-existing autoimmune pathology and should be considered contraindicated until safety data are available.

Conclusion and Next Steps

Decision: Hold

Rationale: Cervical adenofibroma is a benign stromal tumour without established mechanistic links to the PD-1/PD-L1 pathway; a 50% TxGNN prediction score with zero clinical or literature support does not constitute sufficient evidence to advance this indication.

To proceed, the following is needed:

Mechanistic validation: Preclinical data demonstrating PD-L1 expression or immune infiltration in cervical adenofibroma tissue
Safety data: Full package insert review for key warnings and contraindications (source: Health Canada drug product monograph for Jemperli®)
MOA data: DrugBank API query to complete mechanism-of-action documentation
Dataset update: Refresh Canada regulatory dataset to capture current Dostarlimab DIN/approval status
Broader indication review: Indications at higher evidence tiers within this same prediction set — particularly fallopian tube papillary adenocarcinoma (Rank 8, L4, with mechanistic overlap via BRCA/dMMR features) and bladder clear cell adenocarcinoma (Rank 9, L3, with one Phase 2 basket trial: NCT04779151) — merit separate evaluation and may represent more scientifically grounded repurposing candidates for Dostarlimab

This report is for research reference only and does not constitute medical advice. All repurposing candidates require clinical validation before any therapeutic application.

Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.