C4971006: A Study to Learn About the Effects of 2 Study Medicines (Maplirpacept [PF-07901801] and Glofitamab) When Given Together in People With Relapsed or Refractory Diffuse Large B Cell Lymphoma
- Conditions
- Relapsed/Refractory Diffuse Large B Cell Lymphoma
- Registration Number
- 2022-502822-41-00
- Lead Sponsor
- Pfizer Inc.
- Brief Summary
Phase 1b: to assess dose limiting toxicities (DLTs), safety and tolerability of PF-07901801 and glofitamab, after a single dose of obinutuzumab in adult participants with R/R DLBCL in order to select up to 2 doses of PF-07901801 for further evaluation in Phase 2 of the study.
Phase 2: to assess the clinical anti-tumor activity of PF 07901801 in combination with glofitamab after a single dose of obinutuzumab in adult participants with R/R DLBCL.
- Detailed Description
This is a multicenter, open-label, Phase 1b/2 study to evaluate the safety, tolerability and potential clinical benefits of maplirpacept PF-07901801, an anti-CD47 molecule, in combination with fixed doses of glofitamab after a single dose of obinutuzumab in participants with relapsed/refractory (R/R) DLBCL not eligible for or unwilling to undergo high dose chemotherapy and subsequent autologous stem cell transplantation (ASCT) or unable to receive approved chimeric antigen receptor T-cell (CAR-T) therapy (for example, due to logistical limitations).
For Phase 1b, participants must have previously received at least 2 prior systemic treatment regimen. For Phase 2, participants must have received at least 2 but no more than 4 prior systemic treatment regimens. All participants must have previously received an anti-CD20 containing regimen.
Phase 1b will assess dose-limiting toxicities of PF-07901801 when administered in combination with glofitamab, to select doses for the Phase 2 part of the study. Phase 2 will evaluate safety and efficacy to determine the recommended Phase 3 dose of PF-07901801 to be administered in combination with glofitamab.
Recruitment & Eligibility
- Status
- Authorised, recruitment pending
- Sex
- Not specified
- Target Recruitment
- 34
Adults with histologically confirmed DLBCL and relapsed or refractory disease
Participant is not a candidate or unwilling to undergo high dose chemotherapy and subsequent autologous stem cell transplant or unable to receive approved chimeric antigen receptor T-cell therapy (CAR-T).
Measurable disease: at least 1 site of measurable PET-avid disease per Lugano 2014 classification.
Prior treatment must include at least 2 lines of systemic therapy (for Phase 2: at least 2 but no more than 4 prior lines of systemic therapy). Prior therapy must include an anti-CD20 containing regimen.
Adequate hematologic, hepatic and renal function.
Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
High-grade B-Cell lymphoma NOS or High-grade B-Cell lymphoma with MYC and BCL2 rearrangements.
Known or suspected primary or secondary CNS lymphoma or meningeal involvement; history of multifocal leukoencephalopathy; history of CNS disease.
Significant cardiac/cardiovascular/thromboembolic disease.
Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) not resolved within 72 hours prior to study enrollment.
Prior treatment with anti-CD47 and/or anti-SIRPα therapy and/or prior glofitamab or anti-CD20xCD3 containing regimen.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Phase 1b: DLTs during the DLT observation period (21 days following Cycle 1 Day 1) Phase 1b: DLTs during the DLT observation period (21 days following Cycle 1 Day 1)
Phase 2: OR per Lugano Response Classification Criteria 2014 as assessed by the investigator. Phase 2: OR per Lugano Response Classification Criteria 2014 as assessed by the investigator.
- Secondary Outcome Measures
Name Time Method Phase 1b: AEs as characterized by type, frequency, severity (as graded by NCI CTCAE v5.0), timing, seriousness, and relationship to study treatment. Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v5.0), and timing. The severity of CRS and ICANS as assessed according to ASTCT criteria. Phase 1b: AEs as characterized by type, frequency, severity (as graded by NCI CTCAE v5.0), timing, seriousness, and relationship to study treatment. Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v5.0), and timing. The severity of CRS and ICANS as assessed according to ASTCT criteria.
Phase 1b: OR, DoR, CR, DoCR, and PFS per Lugano Response Classification Criteria 2014 as assessed by the investigator. Phase 1b: OR, DoR, CR, DoCR, and PFS per Lugano Response Classification Criteria 2014 as assessed by the investigator.
Phase 1b: Pre- and post-dose concentrations of PF-07901801. Phase 1b: Pre- and post-dose concentrations of PF-07901801.
Phase 1b: ADAs and NAbs against PF-07901801. Phase 1b: ADAs and NAbs against PF-07901801.
Phase 2: DoR, CR, DoCR, and PFS by investigator in participants with measurable disease by investigator per Lugano Response Classification Criteria 2014. Phase 2: DoR, CR, DoCR, and PFS by investigator in participants with measurable disease by investigator per Lugano Response Classification Criteria 2014.
Phase 2: AEs as characterized by type, frequency, severity (as graded by NCI CTCAE V5.0), timing, seriousness, and relationship to study treatment. Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v5.0), and timing. The Severity of CRS and ICANS will be assessed according to ASTCT criteria. Phase 2: AEs as characterized by type, frequency, severity (as graded by NCI CTCAE V5.0), timing, seriousness, and relationship to study treatment. Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v5.0), and timing. The Severity of CRS and ICANS will be assessed according to ASTCT criteria.
Phase 2: Pre- and post-dose concentrations of PF-07901801. Phase 2: Pre- and post-dose concentrations of PF-07901801.
Phase 2: ADAs and NAbs against PF-07901801. Phase 2: ADAs and NAbs against PF-07901801.
Trial Locations
- Locations (18)
Centre Hospitalier Universitaire De Nantes
🇫🇷Nantes, France
Institut Paoli Calmettes
🇫🇷Marseille, France
Hopital Saint Louis
🇫🇷Paris, France
Centre Hospitalier Universitaire De Caen Normandie
🇫🇷Caen Cedex 9, France
Centre Hospitalier De La Cote Basque
🇫🇷Bayonne, France
Hopitaux Universitaires Pitie Salpetriere
🇫🇷Paris, France
Centre Hospitalier Universitaire De Lille
🇫🇷Lille, France
Institut Bergonie
🇫🇷Bordeaux, France
Universitaetsklinikum Halle (Saale) AöR
🇩🇪Halle Saale, Germany
Klinikum der Stadt Ludwigshafen am Rhein gGmbH
🇩🇪Ludwigshafen Am Rhein, Germany
Scroll for more (8 remaining)Centre Hospitalier Universitaire De Nantes🇫🇷Nantes, FranceBenoit TessouinSite contact+33240083271benoit.tessoulin@chu-nantes.fr