A Study of SAR444245 With or Without Other Anticancer Therapies for the Treatment of Adults and Adolescents With Relapsed or Refractory B Cell Lymphoma (Master Protocol) [Pegathor Lymphoma 205]
Study of Investigational Medication for Relapsed or Refractory B Cell Lymphoma
Study Overview
The is a phase 2 multi-cohort, un-controlled, non-randomized, open-label, multi-center study assessing the antitumor activity and safety of non-alpha interleukin (IL-2) SAR444245 with or without other anticancer therapies in participants aged 12 years and older with relapsed or refractory B cell lymphoma. This study is structured as a master protocol with separate sub studies designed to investigate the use of SAR444245 either with or without other anticancer therapies for the treatment of relapsed or refractory B cell lymphoma.
Substudy 1-Cohort A aims to establish safety and preliminary anti-tumor activity for non-alpha interleukin (IL-2) SAR444245 combined with the anti-PD1 antibody, pembrolizumab in trial participants with classic Hodgkin lymphoma (cHL) who are anti-PD-(L)1-naive and have received at least 2 or 3 lines of systemic therapy.
Substudy 3-Cohort C1 aims to establish safety and preliminary anti-tumor activity for SAR444245 as monotherapy in trial participants with diffuse large B-cell lymphoma (DLBCL). Trial participants in this study must have received at least 2 lines of systemic therapy and have either stable or progressive disease 1-3 months post Health Authority approved Chimeric Antigen Receptor T-cell (CAR-T) treatment when given as last systemic treatment prior to study enrollment.
Study Details
The duration of the study for an individual patient will start from the signature of the main informed consent and include:
a screening period of up to 28 days;
a treatment period [max] 35 cycles (21 days per cycle) for Cohort A and 52 cycles (14 days per cycle) for Cohort C1 or until occurrence of unacceptable toxicities or until PD;
an end-of-treatment visit at least approximately 30 days following the last administration of study drug (or until the patient receives another anticancer therapy, whichever is earlier);
and a follow-up visits 3 months after treatment discontinuation and every 3 months thereafter following, until disease progression, or initiation of another antitumor treatment, or death, whichever is earlier.
Eligibility Criteria
You may be eligible for this study if you meet the following criteria:
- Conditions: Classic Hodgkin Lymphoma, Diffuse Large B-cell Lymphoma
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Age: 12 years or above
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Gender: All
Inclusion Criteria:
- Participants must be ≥ 12 years of age, at the time of signing the informed consent
- Disease location amenable to tumor biopsy at baseline
- All participants must have a measurable disease
- Both male and female participants agree to use approved contraception methods; not pregnant or breastfeeding for female participants; no donation or cryopreservation of eggs (ova, oocytes) for female participants and sperms for male participants.
- Capable of giving signed informed consent
For cohort A: Histologically or cytologically confirmed diagnosis of classic Hodgkin lymphoma (cHL), must have received at least two prior lines of systemic therapy for cHL, including at least one containing an anthracycline or brentuximab.
For cohort C1: Histologically confirmed diagnosis of diffuse large B Cell lymphoma (DLBCL), must have received at least two prior lines of systemic therapy for DLBCL, including one containing a combination of anthracycline and rituximab (or another anti-CD20 agent), with the last line of therapy a Health Authority approved CD19-directed CAR-T therapy. Patients must have BOR (Best Overall Response) of stable disease (SD) or progressive disease (PD) after CD-19 directed CAR-T therapy.
Exclusion Criteria:
Participants are excluded from the study if any of the following criteria apply:
- Eastern Cooperative Oncology Group (ECOG) performance status of ≥ 2 (≥ 16 years old). Lansky Scale (< 16 years old) ≤ 60%
- Poor bone marrow reserve
- Poor organ function
- Participants with baseline oxygen saturation (SpO2) ≤ 92% (without oxygen therapy)
- Lymphomatous involvement of the central nervous system
- History of allogenic or solid organ transplant
- Prior IV or subcutaneous anticancer therapy, investigational agent, major surgery within 21 days prior to initiation of IMP; oral anticancer therapy within 5 half-lives or completed palliative radiotherapy within 21 days prior to initiation of IMP
- Has received prior IL-2-based anticancer treatment
- Comorbidity requiring corticosteroid therapy
- Antibiotic use (excluding topical antibiotics) ≤ 14 days prior to first dose of IMP
- Severe or unstable cardiac condition within 6 months prior to starting study treatment
- Active, known, or suspected autoimmune disease that has required systemic treatment in the past 2 years-Known second malignancy either progressing or requiring active treatment within the last 3 years
- Receipt of a live or live attenuated virus vaccination within 28 days of planned treatment start. Seasonal flu vaccines or SARS-CoV-2 vaccine that do not contain live virus are permitted
The above information is not intended to contain all considerations relevant to the potential participation in a clinical trial.
This study investigates the use of an investigational medication called non-alpha interleukin (IL-2) SAR444245 in participants aged 12 years and older with relapsed or refractory B cell lymphoma. The study is divided into different parts, called substudies, to test the medication alone or with other cancer treatments. The goal is to see if the medication is safe and if it can help shrink the tumors in people with this type of cancer. One part of the study looks at how SAR444245 works with another treatment called pembrolizumab in people with classic Hodgkin lymphoma who have not been treated with similar medications before. Another part of the study tests SAR444245 by itself in people with diffuse large B-cell lymphoma who have already tried other treatments.
Participants in this study will undergo a variety of procedures. They will start with a screening period that lasts up to 28 days to ensure they meet all the study requirements. During the treatment period, participants will receive the investigational medication in cycles, which are repeated periods of treatment followed by a rest period. The number of cycles varies depending on the specific part of the study they are in. After finishing the treatment cycles, there will be a follow-up period where participants' health and the status of their cancer will be monitored. This helps researchers understand the long-term effects of the treatment.
- Who can participate: Participants must be 12 years or older with measurable and biopsiable B cell lymphoma and no serious health issues like poor organ function or certain infections. Women must not be pregnant or breastfeeding, and all participants must agree to use contraception.
- Study details: Participants will receive an investigational medication called SAR444245, either alone or with another treatment, and may also receive pembrolizumab in some parts. A placebo is not used in this study.
