Phase 2 Study of Pembrolizumab and Brentuximab Vedotin in Subjects With Relapsed/Refractory CD30 Positive T-cell Lymphoma
This is a single arm, open label, multicenter study phase 2 study of pembrolizumab and brentuximab in subjects with relapsed/refractory CD30 positive T-cell lymphoma (including peripheral T-cell lymphoma and cutaneous T-cell lymphoma) who have received at least one prior therapy. We hypothesize that this combination is effective and will produce an overall response rate of \ 55%. Pembrolizumab and brentuximab will be administered for 16 cycles in subjects with responsive disease. Pembrolizumab will be continued for an additional 19 cycles (total 35 cycles). Response assessments will occur at pre-specified intervals. For the primary endpoint the response assessment after 3 cycles will be taken into consideration. Dose adjustments for specific toxicities with either drug are detailed in the protocol. Based on statistical analysis 32 subjects will need to be accrued to evaluate for disease response based on historical control.
• Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of T-cell Non-Hodgkin lymphoma (T-NHL) will be enrolled in this study.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Histologically confirmed T-cell Non-Hodgkin lymphoma (T-NHL), including:
‣ Peripheral T-cell lymphoma not other specified (PTCL nos)
⁃ Angioimmunoblastic T-cell lymphoma (AITL)
⁃ Anaplastic large-cell lymphoma (ALCL)
⁃ Natural killer (NK)/T-cell lymphoma (nodal or extranodal)
⁃ Cutaneous T-cell lymphoma (CTCL), including mycosis fungoides (MF)/sezary syndrome
⁃ Transformed T-cell lymphoma
⁃ Enteropathy-associated T-cell lymphoma (EATL);
⁃ Subcutaneous panniculitis-like T-cell lymphoma (SCPTCL)
⁃ Hepatosplenic T- cell lymphomas.
• Presence of CD30 (\>1%) by IHC on a previous biopsy sample
• Relapsed/refractory disease having failed at least one prior systemic therapy Note: Single agent Brentuximab could have been a prior line of therapy EXCEPT those with ≥ grade 2 side effects leading to treatment discontinuation or those refractory to Brentuximab
• For patients with peripheral T-cell lymphoma (PTCL): At least one measurable target lesion ≥1.5 cm
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
‣ Not a woman of childbearing potential (WOCBP)
⁃ A woman of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test during screening within 72 hours prior to receiving first dose of protocol-indicated treatment, and must agree to follow instructions for using acceptable contraception from the time of signing consent, and at least 120 days (4 months) after her final dose of pembrolizumab.
• A male participant must agree to use contraception during the treatment period and for at least at least 120 days (4 months) after the final dose of pembrolizumab. and refrain from donating sperm during this period.
⁃ Adequate organ and bone marrow function resulted ≤ 10 days prior to first dose of protocol-indicated treatment: