KEY TAKEAWAYS
- The phase 2 trial KEYNOTE-C11 aimed at assessing the efficacy of sequential pembrolizumab monotherapy and chemotherapy.
- The primary endpoint of this study is to determine the CR as assessed by the BICR using the Lugano 2014 response criteria.
- The secondary endpoints of this study comprise CR as per Lugano 2014 response criteria and rate of PET negativity according to the FDG-PET 5-point scale by BICR.
- Patients who are 60 years of age or older will be administered AVD for a duration of four cycles.
- The use of pembrolizumab followed by conventional chemotherapy has demonstrated clinical efficacy in the initial treatment of classical Hodgkin lymphoma.
Programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors are recognized as established therapeutic modalities for the management of relapsed or refractory classical Hodgkin lymphoma (cHL). According to a recent study published in Blood (Allen PB et al. 2020;137[10]:1318-1326), using the anti-PD-1 antibody pembrolizumab followed by conventional chemotherapy has demonstrated clinical efficacy in the initial treatment of classical Hodgkin lymphoma. The clinical trial, KEYNOTE-C11 (NCT05008224), is an open-label phase 2 study to assess the safety and effectiveness of sequential pembrolizumab monotherapy and chemotherapy, followed by pembrolizumab consolidation in patients who have recently been diagnosed with early unfavorable or advanced-stage classical Hodgkin lymphoma. The eligible candidates for this study are adult patients who have recently been diagnosed with early negative (Ann Arbor stage I/II plus ≥1 NCCN negative risk factor) or advanced-stage (Ann Arbor stage III/IV) cHL and have confirmed histological reports. Patients must meet the Lugano 2014 criteria for measurable disease and have no history of prior radiation therapy, chemotherapy, immunotherapy, or other systemic therapy for classical Hodgkin lymphoma.
All patients will be administered Pembrolizumab 200 milligrams intravenously every three weeks for three cycles, after which a positron emission tomography scan will be conducted to evaluate the patient’s response. After administering pembrolizumab induction therapy, all patients will be subjected to two cycles of doxorubicin, vinblastine, and dacarbazine (AVD) on day 1 and day 15 every four weeks. Subsequently, a third positron emission tomography (PET) scan will be conducted to evaluate the efficacy of the treatment (PET3). Patients who exhibit negative findings on the third positron emission tomography (PET3) scan, with a maximum standardized uptake value (SUV) of 3 on the fluorodeoxyglucose (FDG)-PET 5-point scale, will be administered 2-4 additional cycles of doxorubicin, vinblastine, and dacarbazine (AVD) therapy, based on the stage and bulk of the disease. Patients with the non-bulky early unfavorable disease will receive 2 cycles of AVD, while all others will receive 4 cycles. Patients who exhibit positive findings on PET 3 (≥4 on the FDG-PET 5-point scale) and are below 60 years of age will be recommended to undergo 2-4 cycles of escalated therapy with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone, based on the bulk and stage of the disease.
Patients with non-bulky early unfavorable disease will receive 2 cycles, while all others will receive 4. Patients who are 60 years of age or older will be administered anthracycline, vinblastine, and dacarbazine (AVD) for a duration of four cycles. All patients will subsequently undergo four cycles of pembrolizumab at a dose of 400 milligrams every six weeks as consolidation therapy. The course of treatment shall persist until the occurrence of disease progression, intolerable toxicity, the decision of the investigator, or the attainment of the maximum treatment duration. The adverse events shall be evaluated according to the Common Terminology Criteria for Adverse Events version 5.0. The primary endpoint of this study is to determine the complete response (CR) as assessed by the Blinded Independent Central Review (BICR) using the Lugano 2014 response criteria. The secondary endpoints of this study comprise of complete response (CR) as per Lugano 2014 response criteria, rate of PET negativity according to the FDG-PET 5-point scale by blinded independent central review (BICR), duration of CR as per Lugano 2014 response criteria by BICR, and assessment of safety and tolerability. The exploratory endpoints of this study comprise the 2-year modified progression-free survival (PFS) as evaluated by the Blinded Independent Central Review (BICR) according to the Lugano 2014 response criteria, as well as the overall survival (OS). The efficacy and safety of pembrolizumab will be assessed in all patients who have received at least one dose of the medication. The complete response rate and a 95% confidence interval will be documented using the Clopper-Pearson exact binomial methodology. The duration of complete response, progression-free survival, and overall survival will be estimated by implementing the Kaplan-Meier method. The projected enrollment for this study is 140 patients.
Source:https://meetings.asco.org/abstracts-presentations/213156
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT05008224
Jane N. Winter, Akash Nahar, Eunhee Kim, Patricia Marinello/Sequential pembrolizumab (pembro) and chemotherapy (chemo) in newly diagnosed, early unfavorable, or advanced-stage classical Hodgkin lymphoma (cHL): The phase 2 KEYNOTE-C11 study/J Clin Oncol 40, 2022 (suppl 16; abstr TPS7584) DOI10.1200/JCO.2022.40.16_suppl.TPS7584
