Trial in Progress: Open-Label Phase 1 Study to Evaluate Safety of SGN-35C in Adults with Select Relapsed/Refractory Lymphomas (SGN35C-001)

Background

CD30 regulates immune responses and is expressed in many lymphomas, with limited expression in healthy cells, and is, therefore, a validated therapeutic target in lymphoma. Clinical benefit with brentuximab vedotin (BV), a CD30-directed antibody-drug conjugate (ADC) with a monomethyl auristatin payload, has been observed in lymphoma studies.

SGN-35C is an investigational ADC comprising a chimeric immunoglobulin G1 CD30-directed monoclonal antibody, cAC10, conjugated to a novel topoisomerase I inhibitor via a novel protease-cleavable glucuronide linker. Preclinical data show SGN-35C elicits efficient binding, internalization, and cytotoxicity in CD30+ tumor cells, and induces antitumor activity via direct cytotoxicity and bystander effect, including in BV-resistant lymphoma models. Unlike BV, SGN-35C is not thought to cause peripheral neuropathy due to a different payload. These data provide a robust rationale to clinically develop SGN-35C.

Study Design and Methods

SGN35C-001 (NCT06254495) is a first-in-human, open-label, multicenter, global, phase 1 dose-escalation and dose-expansion study to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and antitumor activity of SGN-35C in patients with select relapsed/refractory (R/R) lymphomas. Patients will be enrolled in dose-escalation (Part A), optional dose-optimization (Part B), dose-expansion (Part C), and optional biology cohorts. Patients in Part A will receive SGN-35C intravenously across various doses. Part B dosing may evaluate doses from Part A. Part C and biology cohort dosing will occur at the recommended dose from Parts A and B. The biology cohort may enroll patients from Parts A, B and C, who consent to protocol-specified research biopsies.

For Parts A and B, patients must have histologically confirmed R/R classical Hodgkin lymphoma, peripheral T-cell lymphoma (PTCL), or diffuse large B-cell lymphoma (DLBCL) with no appropriate standard therapy available. Patients with PTCL or DLBCL must have CD30 expression ≥1% in tumor tissue from the most recent biopsy or obtained at or after relapse by local testing. For Part C, patients are eligible irrespective of CD30 expression and must provide tumor tissue for evaluation. All patients must be ≥18 years of age and have measurable disease per Lugano as documented by radiographic criteria and an Eastern Cooperative Oncology Group performance status ≤1. Key exclusion criteria include history of another malignancy within 3 years of first dose, active cerebral/meningeal disease, autologous stem cell transplant (SCT) within 12 weeks of first dose, allogeneic SCT in <100 days, active acute or chronic graft vs host disease and having received immunosuppressive therapy for graft vs host disease, significant cytomegalovirus infection, grade ≥2 pulmonary or interstitial lung disease, or clinically significant lung disease requiring treatment with systemic corticosteroids 6 months prior to enrollment, or those with history of clinically significant GI issues.

Primary endpoints include type, incidence, and severity of adverse events and laboratory abnormalities, frequency of dose modifications, and incidence of dose-limiting toxicities. Secondary endpoints include PK parameters, incidence of antidrug antibodies, objective response rate, duration of response, and complete response rate. Enrollment is ongoing in the US and planned globally.