Dana-Farber Cancer Institute is advancing two Phase II clinical trials that explore immunotherapy applications across different cancer types, with one study targeting progressive meningiomas using nivolumab and another investigating neoadjuvant dostarlimab in melanoma patients.
Meningioma Immunotherapy Trial
The open-label Phase II study (15-490) evaluates nivolumab, either as monotherapy or combined with radiation therapy, in patients with progressive or recurrent meningiomas. The trial accepts patients with histologically confirmed WHO grade I, II, or III meningiomas, including metastatic cases. Notably, patients with grade I tumors must have previously failed radiation therapy to be eligible.
The study places no restrictions on the number of prior treatments, allowing patients who have undergone multiple surgeries, radiation therapies, radiosurgery treatments, or systemic therapeutic agents. However, specific timing requirements apply: patients must wait at least 12 weeks after completing radiation therapy before starting study treatment, unless there is histopathologic confirmation of recurrent tumor or new enhancing tumor outside the radiation field.
Eligible participants must be at least 18 years old with a Karnofsky performance status of 70 or higher. The trial requires adequate organ and marrow function, including white blood cell count ≥2000/mm³, absolute neutrophil count ≥1,000/mm³, and platelet count ≥100,000/mm³. Patients must also maintain stable or decreasing corticosteroid doses for at least five days prior to baseline imaging.
The study excludes patients with tumors primarily localized to the brainstem or spinal cord, those with evidence of significant intratumoral hemorrhage, and individuals who have received prior PD-1 or PD-L1 directed therapy. For the combination cohort, previous CTLA-4 directed therapy is also exclusionary.
Neoadjuvant Melanoma Study
The Phase II neoadjuvant study (21-201) investigates dostarlimab (TSR-042) in patients with cutaneous or unknown primary melanoma, excluding uveal, choroidal, and mucosal melanoma subtypes. The trial targets patients with AJCC 8th edition TNM stages including various nodal involvement patterns (N1b, N1c, N2b, N2c, N3b, N3c) and/or distant metastases (M1a, M1b).
Patient eligibility encompasses several clinical scenarios: primary melanoma with clinically apparent regional lymph node metastases, clinically detected recurrent melanoma at regional lymph node basins, primary melanoma involving multiple regional nodal groups, and in-transit or satellite metastases with or without regional lymph node involvement. The study also includes patients with oligometastatic lung disease deemed resectable at baseline.
Participants must demonstrate measurable disease based on RECIST 1.1 criteria and provide tumor tissue from newly obtained biopsies. The trial requires ECOG Performance Scale scores of 0 or 1 and adequate organ function as determined by screening laboratories within 14 days of registration.
Treatment Restrictions and Safety Considerations
Both trials implement strict exclusion criteria regarding concurrent treatments and medical conditions. The meningioma study prohibits high-dose systemic corticosteroids defined as dexamethasone >4 mg/day or bioequivalent for at least three consecutive days within two weeks prior to treatment initiation. The melanoma trial excludes patients receiving systemic immunosuppression with corticosteroids >10mg daily prednisone equivalent.
Neither study permits patients with active autoimmune diseases requiring systemic treatment, active infections requiring intravenous or systemic therapy, or evidence of interstitial lung disease. Both trials exclude individuals with known HIV infection, hepatitis B or C infections, and those who have received live vaccines within 30 days of study initiation.
Contraceptive Requirements
Both studies mandate comprehensive contraceptive measures for participants of reproductive potential. The meningioma trial requires women of childbearing potential to use contraception for the duration of treatment plus five months after the last nivolumab dose, while men must use contraception for seven months post-treatment. The melanoma study requires similar precautions throughout the projected trial duration.
These trials represent Dana-Farber's continued investigation into immunotherapy applications across different tumor types, with each study tailored to address the specific clinical challenges and treatment landscapes of meningioma and melanoma patients.
