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| Ref Type | Journal Article | ||||||||||||
| PMID | (32364844) | ||||||||||||
| Authors | Capdevila J, Wirth LJ, Ernst T, Ponce Aix S, Lin CC, Ramlau R, Butler MO, Delord JP, Gelderblom H, Ascierto PA, Fasolo A, Führer D, Hütter-Krönke ML, Forde PM, Wrona A, Santoro A, Sadow PM, Szpakowski S, Wu H, Bostel G, Faris J, Cameron S, Varga A, Taylor M | ||||||||||||
| Title | PD-1 Blockade in Anaplastic Thyroid Carcinoma. | ||||||||||||
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| Abstract Text | Anaplastic thyroid carcinoma is an aggressive malignancy that is almost always fatal and lacks effective systemic treatment options for patients with BRAF-wild type disease. As part of a phase I/II study in patients with advanced/metastatic solid tumors, patients with anaplastic thyroid carcinoma were treated with spartalizumab, a humanized monoclonal antibody against the programmed death-1 (PD-1) receptor.We enrolled patients with locally advanced and/or metastatic anaplastic thyroid carcinoma in a phase II cohort of the study. Patients received 400 mg spartalizumab intravenously, once every 4 weeks. The overall response rate was determined according to RECIST v1.1.Forty-two patients were enrolled. Adverse events were consistent with those previously observed with PD-1 blockade. Most common treatment-related adverse events were diarrhea (12%), pruritus (12%), fatigue (7%), and pyrexia (7%). The overall response rate was 19%, including three patients with a complete response and five with a partial response. Most patients had baseline tumor biopsies positive for PD-L1 expression (n = 28/40 evaluable), and response rates were higher in PD-L1-positive (8/28; 29%) versus PD-L1-negative (0/12; 0%) patients. The highest rate of response was observed in the subset of patients with PD-L1 ≥ 50% (6/17; 35%). Responses were seen in both BRAF-nonmutant and BRAF-mutant patients and were durable, with a 1-year survival of 52.1% in the PD-L1-positive population.To our knowledge, this is the first clinical trial to show responsiveness of anaplastic thyroid carcinoma to PD-1 blockade. | ||||||||||||
| Molecular Profile | Treatment Approach |
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| Gene Name | Source | Synonyms | Protein Domains | Gene Description | Gene Role |
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| Therapy Name | Drugs | Efficacy Evidence | Clinical Trials |
|---|---|---|---|
| Spartalizumab | Spartalizumab | 2 | 10 |
| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
|---|---|---|---|---|
| Spartalizumab | PDR001|PDR-001 | Immune Checkpoint Inhibitor 149 PD-L1/PD-1 antibody 122 | Spartalizumab (PDR001) is a monoclonal antibody that targets PD-1 (PDCD1) and inhibits binding of the PD-L1 (CD274) ligand, potentially resulting in enhanced anti-tumor immune response (PMID: 32364844, PMID: 32179633). |
| Gene | Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| CD274 positive | anaplastic thyroid carcinoma | predicted - sensitive | Spartalizumab | Phase II | Actionable | In a Phase II trial, Spartalizumab (PDR001) was tolerated in patients with anaplastic thyroid carcinoma, and resulted in an overall response rate (ORR) of 19% (8/42, 3 complete responses, 5 partial responses), median progression-free survival of 1.7 mo, and median overall survival of 5.9 mo; ORR was higher in patients with tumor PD-L1 >=1% compared to PD-L1<1% (29%, 8/28 vs 0%, 0/12, p=0.079), and highest ORR (35%) was observed in patients with PD-L1 >= 50% (PMID: 32364844; NCT02404441). | 32364844 |