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A Phase 1/2, Open-label, Multicenter Study to Investigate the Safety, Pharmacokinetics, and Efficacy of Fadraciclib (CYC065), an Oral CDK2/9 Inhibitor, in Subjects With Advanced Solid Tumors and Lymphoma

ABSTRACT: Primary objectives: Phase 1: To determine the maximum-tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of fadraciclib when administered orally twice daily (BID) in 28-day cycles in adult subjects with advanced solid tumors and lymphoma Phase 2: To evaluate preliminary efficacy of fadraciclib as measured by overall response rate (ORR) in subjects with locally advanced, recurrent, or metastatic, histologically confirmed advanced solid tumors or lymphoma who have failed all standard therapies or for whom standard therapy does not exist Primary endpoints: Phase 1: The incidence rate of dose-limiting toxicities (first cycle only) at each dose level Phase 2:ORR according to Response Evaluation Criteria in Solid Tumors: RECIST guidelines (Lugano Criteria for lymphoma, mSWAT for CTCL) for each tumor type

DISEASE(S): Ovarian Cancer Nos,Hormone Receptor Positive Breast Cancer,Malignant Solid Tumor,Her2 Positive Breast Cancer,Metastatic Breast Cancer,B-cell Lymphoma,Triple Negative Breast Cancer,Breast Cancer,Malignant Neoplasm Of Biliary Tract, Part Unspecified,Her2 Negative Breast Cancer,T-cell Lymphoma,Colorectal Cancer Metastatic,Endometrial Cancer Nos,Cáncer De Endometrio, Cáncer De Ovario, Cáncer De Las Vías Biliares, Carcinoma Hepatocelular (chc), Linfoma De Linfocitos B, Linfoma De Linfocitos T, Cáncer Colorrectal Metastásico, Cáncer De Mama (her-2 Metastásico Refractario, Receptor Hormonal +, Her-2 Negativo E Inhibidor De Mbc Post-cdk4 / 6, Triple Negativo)cohorte De Cesta: Tipos De Tumores Que Se Sospecha Que Tienen Un Mecanismo De Acción Relacionado Y No Están Incluido En Los Grupos Anteriores,Endometrial Cancer, Ovarian Cancer, Biliary Tract Cancer, Hepatocellular Carcinoma, B-cell Lymphoma, T-cell Lymphoma, Metastatic Colorectal Cancer, Breast Cancer (metastatic Her-2 Refractory, Hormone Receptor +, Her-2 Negative, And Mbc Post-cdk4/6 Inhibitor, Triple-negative)basket Cohort: Tumor Types That Are Suspected To Have A Related Mechanism Of Action And Are Not Included In Previous Groups,Hepatocellular Carcinoma

PROVIDER: 2541477 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:Afamitresgene autoleucel, an HLA-restricted autologous specific peptide enhanced affinity receptor (SPEAR) T-cell therapy targeting MAGE-A4, was developed to treat HLA-A*02 positive patients with MAGE-A4 expressing solid tumors. A multicenter, dose-escalation, Phase 1 trial (NCT03132922) was conducted evaluating afamitresgene autoleucel in patients with relapsed or refractory (≥1 prior line of therapy) metastatic solid tumors. The primary endpoint was safety. The secondary endpoint was anti-tumor activity including overall response rate, best overall response, time to response, duration of response, duration of stable disease, progression-free survival and overall survival. Thirty-eight patients were treated with afamitresgene autoleucel across 9 tumor types, including 16 with synovial sarcoma (SS). Overall, afamitresgene autoleucel was well tolerated. The most common adverse events were cytopenias. Cytokine release syndrome occurred in 55% of all patients with severity grade ≤2 in 90% of reported cases. Overall response rate (ORR) was 24% and disease control rate (DCR) was 74% with objective responses in 7 patients with SS, 1 patient with non-small cell lung cancer, and 1 patient with head and neck squamous cell carcinoma. ORR in patients with SS, all prior treated with ifosfamide chemotherapy, was 44%, and DCR was 94%. Median progression-free survival and overall survival were 20.4 weeks (95% CI: 10.0, 52.1) and 58.1 weeks (95% CI: 36.3,-), respectively, for patients with SS and 12.3 weeks (95% CI: 10.857, 19.1) and 42.9 weeks (95% CI: 20.7, -), respectively, for the overall population. Translational findings demonstrated that afamitresgene autoleucel infiltrates into tumors, has an IFNγ-driven mechanism-of-action, and triggers adaptive immune responses. Overall, afamitresgene autoleucel has an acceptable safety profile with early and durable responses in HLA-A*02 positive patients with MAGE-A4 expressing solid tumors, especially in patients with metastatic SS. The recommended treatment regimen for Phase 2 evaluation involves lymphodepleting chemotherapy consisting of cyclophosphamide 600 mg/m2 x 3 days and fludarabine 30 mg/m2 x 4 days followed by afamitresgene autoleucel at a dose range of 1 to 10 billion transduced T-cells.

Dataset Information

A Phase 1/2, Open-label, Multicenter Study to Investigate the Safety, Pharmacokinetics, and Efficacy of Fadraciclib (CYC065), an Oral CDK2/9 Inhibitor, in Subjects With Advanced Solid Tumors and Lymphoma

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