Prolgolimab Monotherapy or in Combination With Bendamustine for r/r Classical Hodgkin Lymphoma

Study Overview
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Brief Summary
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Prolgolimab is an anti-PD-1 inhibitor that has previously been shown to be effective and safe for the treatment of patients with melanoma. Given the mechanism of action, it is expected to be effective in patients with classical Hodgkin lymphoma (cHL). The use of PD-1 inhibitors in 2nd line treatment, as part of PET-adapted monotherapy/combination therapy, has already demonstrated a favorable toxicity profile, as well as a high efficacy, which may lead to increased survival of patients with r/r cHL. It has been demonstrated that long-term disease remission can be achieved after PD-1 inhibitor therapy, even in a group of heavily pretreated patients with relapsed/refractory cHL. The use of prolgolimab as part of PET-adapted therapy strategy in this study may allow to achieve a prolonged remission in patients with cHL who are highly sensitive to immunotherapy while omitting the autologous stem cell transplantation.

Official Title
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Efficacy and Safety Study of Second-Line Prolgolimab Monotherapy or in Combination With Bendamustine for Relapsed/Refractory Classical Hodgkin Lymphoma

Conditions
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Hodgkin Lymphoma

Intervention / Treatment
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* Drug: Prolgolimab
* Drug: Combination with prolgolimab and bendamustine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a histologically verified diagnosis of cHL, refractory or relapsed after the first line of therapy Age 18-70 y Ejection fraction not less than 50% No severe concurrent illness 0-2 ECOG status Use of highly effective contraceptive methods from the moment of signing the informed consent form, throughout the study and within 6 months after receiving the last dose of the drug. Exclusion Criteria: Severe organ failure: creatinine > 2 norms; alanine aminotransferase, aspartate aminotransferase > 5 norms; bilirubin> 1.5 norms; Respiratory failure > grade 1 at the time of enrollment Requirement for vasopressor support at the time of enrollment Uncontrolled bacterial or fungal infection at the time of enrollment Active or prior documented autoimmune disease requiring systemic treatment Pregnancy, breastfeeding, planning pregnancy or parenthood during the study period Hypersensitivity or allergy to study drugs Somatic or mental pathology that does not allow to perform research procedures, including the signing of informed consent Simultaneous use of drugs or medical devices studied in other clinical trials Use of PD-1 inhibitors or bendamustine in the 1st line of therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Main arm<br>Patients receive 6 cycles of prolgolimab monotherapy with subsequent assessment of response by PET/CT using Lugano and LYRIC criteria. Patients with complete response continue prolgolimab therapy for up to 24 cycles. Patients are switched to combination therapy with prolgolimab and chemotherapy (bendamustine) if the complete response is not achieved after 6 cycles of therapy or in case of relapse during prolgolimab monotherapy. Patients without complete response after 6 cycles of prolgolimab monotherapy or with relapse during monotherapy will receive 3 cycles of combination therapy with prolgolimab and bendamustine every 28 days. Collection of hematopoietic stem cells is performed at any stage of combination therapy. Response evaluation after 3 cycles of combination therapy is performed by PET/CT using Lugano and LYRIC criteria. Autologous stem cell transplantation is conducted in patients who achieve complete or partial response. | Drug: Prolgolimab<br>* Prolgolimab monotherapy 1 mg/kg IV every 2 weeks up to a maximum of 24 cycles<br>Drug: Combination with prolgolimab and bendamustine<br>* Prolgolimab 1 mg/kg IV D1,15; Bendamustine 90 mg/m2 IV D1,2, 28-day cycle, maximum of 3 cycles;<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate during prolgolimab monotherapy | Overall response rate (ORR), defined as the proportion of patients with complete response (CR) or partial response (PR) in measurable lesions as defined by Lugano and LYRIC criteria | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of grade 3 or higher treatment-related adverse events during prolgolimab monotherapy | Toxicity was graded according to NCI CTCAE 5.0.(Common Terminology Criteria for Adverse Events Version 5.0) | 12 months | 
| Frequency of grade 3 or higher treatment-related adverse events during combination therapy (prolgolimab+bendamustine) | Toxicity was graded according to NCI CTCAE 5.0.(Common Terminology Criteria for Adverse Events Version 5.0) | 24 months | 
| Overall response rate during combination therapy (prolgolimab+bendamustine) | Overall response rate (ORR), defined as the proportion of patients with complete response (CR) or partial response (PR) in measurable lesions as defined by Lugano and LYRIC criteria | 24 months | 
| 1-year and 2-year overall survival | Overall survival defined as the time from the protocol therapy initiation to death from any reason | 24 months | 
| 1-year and 2-year progression-free survival | Progression-free survival defined as the time from the protocol therapy initiation to disease progression, relapse or death from any reason. | 24 months | 
| Duration of response | Duration of response was defined as the time from response achievement to disease progression, relapse or death from any reason | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hodgkin lymphoma, Prolgolimab, PD-1 inhibitors, Bendamustine, Immunotherapy, Relapsed/refractory, Autologous stem cell transplantation,