Clinical trial NCT05179603: 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]
Official title: Phase 2 Non-randomized, Open-label, Multi-cohort, Multicenter Study Assessing the Clinical Benefit of SAR444245 (THOR-707) With or Without Other Anticancer Therapies for the Treatment of Adults and Adolescents With Relapsed or Refractory B Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Classic Hodgkin Lymphoma
Diffuse Large B-cell Lymphoma
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2022-01-05
Enrollment: 14
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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: 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.

Primary outcomes:
measure: Complete Response Rate- Cohort A
timeFrame: Baseline to the date of first documented progression or initiation of subsequent anticancer therapy or approximately 8 months after the last participant receive first dose.
measure: Objective Response Rate- Cohort C1
timeFrame: Baseline to the date of first documented progression or initiation of subsequent anticancer therapy or approximately 8 months after the last participant receive first dose.
Secondary outcomes:
measure: Incidence of Dose-limiting toxicities (DLTs)
timeFrame: 21 days for Cohort A and 28 days for Cohort C1
measure: Incidence of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and laboratory abnormalities
timeFrame: From first investigational medicinal product (IMP) dose up to 30 days for TEAEs or up to 90 days for SAE after the last dose of IMP i.e., up to approximately 27 months
measure: Objective Response Rate- Cohort A
timeFrame: Baseline to the date of first documented progression or initiation of subsequent anticancer therapy or approximately 8 months after the last participant receive first dose.
measure: Time to Response (TTR)
timeFrame: From the date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 36 months
measure: Duration of Response (DoR)
timeFrame: From the date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 36 months
measure: Clinical Benefit Rate (CBR)
timeFrame: Baseline to the date of first documented progression or initiation of subsequent anticancer therapy or approximately 8 months after the last participant receive first dose.
measure: Progression free survival (PFS)
timeFrame: From the date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 36 months
measure: Complete response rate- Cohort C1
timeFrame: Baseline to the date of first documented progression or initiation of subsequent anticancer therapy or approximately 8 months after the last participant receive first dose.
measure: Plasma concentration of SAR444245
timeFrame: Multiple timepoints up to approximately 24 months
measure: Incidence of anti-drug antibodies (ADAs) against SAR444245
timeFrame: Multiple timepoints up to approximately 24 months
Other outcomes:
Locations:
city: Caba
country: Argentina
facility: Investigational Site Number : 0320005
state: Buenos Aires
city: Santiago
country: Chile
facility: Investigational Site Number : 1520003
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number : 1520002
state: Reg Metropolitana De Santiago
city: Vina del Mar
country: Chile
facility: Investigational Site Number : 1520004
state: Valparaíso
city: Temuco
country: Chile
facility: Investigational Site Number : 1520001
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240002
state: Barcelona [Barcelona]
city: Hospitalet de Llobregat
country: Spain
facility: Investigational Site Number : 7240001
state: Barcelona [Barcelona]
city: Madrid / Madrid
country: Spain
facility: Investigational Site Number : 7240004
state: Madrid, Comunidad De
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: