PrimaryPhase 1-To characterize the safety and tolerability of isatuximab in combination with cemiplimab in participants with relapsed and refractory cHL, DLBCL or PTCL, and to confirm the recommended Phase 2 dose (RP2D).Phase 2- Cohort A1 (anti-…
ID
Source
Brief title
Condition
- Other condition
- Lymphomas Hodgkin's disease
- Lymphomas non-Hodgkin's B-cell
Synonym
Health condition
non-Hodgkin Peripheral T-cell lymfomen
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Phase 1: Dose limiting toxicities (DLTs), Recommended Phase 2 dose (RP2D)
Phase 2: Cohort A1: Complete Remission Rate. Cohorts A2, B, and C: Response
Rate
Secondary outcome
Adverse Events (AEs)/Serious Adverse Events (SAEs) for isatuximab + cemiplimab
Adverse Events/Serious Adverse Events for isatuximab + cemiplimab + radiotherapy
-Immunogenicity
-Pharmacokinetic evaluation.
-Tumor burden change
-Disease control rate
-Duration of response
-Progression free survival
Background summary
Monoclonal antibodies that block the programmed cell death/programmed cell
death-ligand (PD-1, PD-L1) axis alone have demonstrated benefit in lymphoma
therapy. Drugs that inhibit/block the anti-PD-1/PD-L1 axis are known as
checkpoint inhibitors, which are regulators of the immune system. These
pathways are increasingly considered as new targets for cancer immunotherapy
due to their potential use in multiple types of cancers.
A greater anti-tumor immune response could be triggered by combining anti-PD-L1
and CD38 antibodies than anti-PD-L1 monotherapy alone, and possibly revert
resistance to anti-PD-1/PD-L1 therapies.
CD38 expression is well-documented in hematological cancers. In lymphomas, CD38
is found expressed on the tumor cells of classic Hodgkin lymphoma (cHL),
diffuse large B cell lymphoma (DLBCL), and peripheral T-cell lymphoma (PTCL).
Isatuximab (anti-CD38 antibody) can induce different immune-modulatory
mechanisms that can contribute to reshape the tumor microenvironment and
enhance the anti-tumor activity of anti-PD-1 antibodies.
Although isatuximab has not been tested in lymphoma, this study is designated
to explore whether isatuximab may contribute to reshaping the tumor
immune-environment and will enhance the activity of checkpoint inhibitor
therapy.
Study objective
Primary
Phase 1
-To characterize the safety and tolerability of isatuximab in combination with
cemiplimab in participants with relapsed and refractory cHL, DLBCL or PTCL, and
to confirm the recommended Phase 2 dose (RP2D).
Phase 2
- Cohort A1 (anti-programmed cell death protein 1/ligand 1 [PD-1/PD-L1] naive
cHL): To assess the complete remission (CR) rate of isatuximab in combination
with cemiplimab.
- Cohort A2 (cHL progressing from PD-1/PD-L1), B (DLBCL) and C (PTCL): To
assess the objective response rate (ORR) of isatuximab in combination with
cemiplimab.
Secondary
- To evaluate the safety of the RP2D of the combination of isatuximab with
cemiplimab.
- To evaluate the safety of the combination of isatuximab with cemiplimab and
radiotherapy in patients with cHL.
- To evaluate the immunogenicity of isatuximab and cemiplimab when given in
combination.
- To characterize the pharmacokinetic (PK) profile of isatuximab and cemiplimab
when given in combination.
-To assess overall efficacy of isatuximab in combination with cemiplimab and
isatuximab in combination with cemiplimab and radiotherapy.
Study design
Phase 1/2, non-randomized, open-label single arm.
Intervention
Isatuximab (IV) and cemiplimab (IV)
Radiation therapy in naïve lesions (Standard of Care)
Study burden and risks
The risks are related to blood draws, CT or PET scan (radiation burden), biopsy
and possible side effects of the study medication.
Paasheuvelweg 25 -
Amsterdam 1105 BP
NL
Paasheuvelweg 25 -
Amsterdam 1105 BP
NL
Listed location countries
Age
Inclusion criteria
- Participants must be >= 18 years of age inclusive, at the time of signing the
informed consent, - Disease location amenable to tumor biopsy at baseline, -
Measurable disease, - For Cohort A1 (classic Hodgkin's lymphoma [cHL]
anti-programmed cell death protein 1/ligand 1 [PD-1/PD-L1] inhibitor naïve):
Histologically confirmed advanced cHL that has relapsed or progressed after at
least 3 lines of systemic therapy that may include autologous hematopoietic
stem cell transplant (auto-HSCT) or auto-HSCT and brentuximab vedontin (BV), -
For Cohort A2 (cHL anti-PD-1/PD-L1inhibitor progressor): Histologically
confirmed advanced cHL which has relapsed or progressed after one previous
anti-PD-1/PD-L1 containing regimen as the most recent prior therapy but no more
than 4 lines of previous chemotherapy including the anti-PD-1/PD-L1 containing
regimen and documentation of benefit during or after the anti-PD-1/PD-L1
containing regimen within 4 months prior to initiation of investigational
medicinal product (IMP), - For Cohort B (diffuse large B-cell lymphoma
[DLBCL]):Histologically confirmed advanced DLBCL that has relapsed or
progressed after 2 lines of systemic therapy including auto-HSCT or 2 lines of
systemic therapy for participants who are not eligible for auto-HSCT, - For
Cohort C (peripheral T-cell lymphoma [PTCL]): Histologically confirmed advanced
PTCL that has relapsed or progressed after either first-line chemotherapy and
auto-HSCT as consolidation of first remission or first-line chemotherapy if
participants are ineligible for auto-HSCT, - Body weight of > 45 kg
Exclusion criteria
-Prior exposure to agent that blocks CD38, - For patients with cHL (PD-1/PD-L1
naïve), DLBCL or PTCL prior exposure to any agent (approved or investigational)
that blocks the PD-1/PD-L1, PD-L2, CD137, CTLA-4 or LAG-3, - Evidence of other
immune related disease /conditions, - Has received a live-virus vaccination
within 28 days of planned treatment start; seasonal flu vaccines that do not
contain live virus are permitted, - Eastern Cooperative Oncology Group (ECOG)
performance status (PS) >=2, - Poor bone marrow reserve, - Poor organ function
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2018-002442-37-NL |
| Other | EudraCT: 2018-002442-37 |
| CCMO | NL67653.068.18 |