A Study to Learn About the Effects of Two Study Medicines (Maplirpacept [PF-07901801] And Glofitamab) When Given Together In People With Relapsed Or Refractory Diffuse Large B Cell Lymphoma.

JRCT ID: jRCT2071230043

Registered date:19/07/2023

Basic Information

• Recruitment status: Pending
• Health condition(s) or Problem(s) studied: Diffuse Large B-Cell Lymphoma
• Date of first enrollment: 31/07/2023
• Target sample size: 70
• Countries of recruitment: United States,Japan
• Study type: Interventional

Intervention(s)

Experimental: Phase 1b
Participants will be allocated to sequential dose levels of PF-07901801, administered in combination with fixed doses of glofitamab after a dose of obinutuzumab, to select two doses of PF-07901801 for further evaluation in Phase 2. Approximately 20 participants will be enrolled.
Interventions:
* Drug: Maplirpacept (PF-07901801)
Intravenous infusion
* Drug: Glofitamab
Intravenous infusion
* Drug: Obinutuzumab
Intravenous infusion

Experimental: Phase 2
Participants will be randomized to 1 of 2 different dose levels of PF-07901801 which will be administered in combination with fixed doses of glofitamab after a dose of obinutuzumab. Approximately 50 participants will be enrolled (25 per dose).
Interventions:
* Drug: Maplirpacept (PF-07901801)
Intravenous infusion
* Drug: Glofitamab
Intravenous infusion
* Drug: Obinutuzumab
Intravenous infusion

Everyone in this study will receive all three medicines at the study site by intravenous (IV) infusion which is given directly into a vein. The two study medicines (maplirpacept [PF-07901801] and glofitamab) will be given in 21-day cycles.

At Cycle 0, participants will receive a single dose of obinutuzumab pre-treatment followed by two step-up doses of glofitamab. The combination of maplirpacept (PF-07901801) with glofitamab full dose will be administered for the first time at Cycle 1 Day 1.

Maplirpacept (PF-07901801) will be given weekly for the first three cycles and then every three weeks. Glofitamab will be given every 3 weeks for approximately 9 months. Thereafter participants will continue to receive maplirpacept alone.

Maplirpacept (PF-07901801) will be given at different doses to different participants. Everyone taking part will receive the same fixed doses of glofitamab and obinutuzumab studied in patients with DLBCL.

Outcome(s)

Primary Outcome

Primary Outcome Measures :
1. Phase 1b: Number of participants with Dose limiting toxicities (DLT) [ Time Frame: 21 days following first PF-07901801 dose ]
DLTs are a predefined set of adverse events that are at least possibly related to any or all of the investigational agents.

2. Phase 2: Objective Response (OR) [ Time Frame: Time from the date of first dose of study intervention until the first documentation of disease progression, death, or start of new anticancer therapy (assessed up to approximately 24 months) ]
OR defined as proportion of participants with objective response based assessment of complete response (CR) or partial response (PR) according to Lugano Response Classification Criteria 2014.

Secondary Outcome

Secondary Outcome Measures :
1. Phase 1b and Phase 2: Frequency of adverse events (AE) [ Time Frame: Time from the date of first dose of study intervention through 28 days after last dose of PF-07901801 or 90 days after last dose of glofitamab or obinutuzumab (assessed up to approximately 24 months) ]
Type and severity (severity according to the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], version 5.0). Severity of Cytokine Release Syndrome (CRS) and Immune effector cell-associated neurotoxicity syndrome (ICANS) assessed according to ASTCT criteria.

2. Phase 1b and Phase 2: Frequency of clinical laboratory abnormalities [ Time Frame: Time from the date of first dose of study intervention through 28 days after last dose of PF-07901801 or 90 days after last dose of glofitamab or obinutuzumab (assessed up to approximately 24 months) ]
Type and severity (severity according to the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], version 5.0).

3. Phase 1b: Objective Response (OR) [ Time Frame: Time from the date of first dose of study intervention until the first documentation of disease progression, death, or start of new anticancer therapy (assessed up to approximately 24 months) ]
OR defined as proportion of participants with objective response based assessment of complete response (CR) or partial response (PR) according to Lugano Response Classification Criteria 2014.

4. Phase 1b and Phase 2: Duration of Response (DoR) [ Time Frame: Time from the date of first dose of study intervention until the first documentation of disease progression, death, or start of new anticancer therapy (assessed up to approximately 24 months) ]
DoR defined as the time from the first documentation of OR until progressive disease (PD), or death due to any cause, whichever occurs first.

5. Phase 1b and Phase 2: Complete Response (CR) [ Time Frame: Time from the date of first dose of study intervention until the first documentation of disease progression, death, or start of new anticancer therapy (assessed up to approximately 24 months) ]
CR defined per Lugano Response Classification Criteria 2014

6. Phase 1b and Phase 2: Duration of Complete Response (DoCR) [ Time Frame: Time from the date of first dose of study intervention until PD, or death due to any cause, whichever occurs first (assessed up to approximately 24 months) ]
DoCR defined as the time from the first documentation of a CR until PD, or death due to any cause, whichever occurs first.

7. Phase 1b and Phase 2: Progression Free Survival (PFS) [ Time Frame: Time from the date of first dose of study intervention until PD, or death due to any cause, whichever occurs first (assessed up to approximately 24 months) ]
PFS is defined as the time from the date of first dose until PD per Lugano Response Classification Criteria 2014, or death due to any cause, whichever occurs first.

8. Phase 1b and Phase 2: Serum Concentration Versus Time Summary of PF-07901801 [ Time Frame: Pre and post-infusion on Day 1 of Cycle 1 and 2 (each cycle is 21 days), Pre-infusion on Day 8 of Cycle 1, Pre-infusion on Day 1 of Cycles 3, 4, 5, 7, 10, 13 and every 6 cycle thereafter until end of treatment (approximately 24 months) ]
Pre- and post-dose concentrations of PF-07901801

9. Phase 1b and Phase 2: Serum Concentration Versus Time Summary of glofitamab [ Time Frame: Pre-infusion on Days 8 and 15 of Cycle 0 (cycle duration is 21 days), Pre-infusion, post-Infusion on Day 1 of Cycle 1 and 2, Pre-infusion on Day 1 of Cycle 3, 4, 7, 10 and 12. ]
pre- and post-dose concentrations of glofitamab

10. Phase 1b and Phase 2: Number of participants with Anti-Drug Antibody (ADA) against PF-07901801 [ Time Frame: On the first day of every 21-day cycle through 5 cycles, then every third cycle from cycle 7 through cycle 13 and then every sixth cycle thereafter until end of PF-07901801 treatment (assessed up to approximately 24 months) ]
To evaluate immunogenicity of PF-07901801

11. Phase 1b and Phase 2: Number of participants with Anti-Drug Antibody (ADA) against glofitamab [ Time Frame: On the 8th day of cycle 0 (cycle duration is 21 days), then the first day of every 21-day cycle through cycle 4, then the first day of cycle 7, 10 and 12 (last assessment). ]
To evaluate immunogenicity of glofitamab

12. Phase 1b and Phase 2: Number of participants with Neutralizing antibody (NAb) for PF-07901801 [ Time Frame: On the first day of every 21-day cycle through 5 cycles, then every third cycle from cycle 7 through cycle 13 and then every sixth cycle thereafter until end of PF-07901801 treatment (assessed up to approximately 24 months) ]
To evaluate immunogenicity of PF-07901801

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Key Inclusion Criteria:
* Histologically confirmed diagnosis of DLBCL
* Relapsed or refractory disease
* Participant is not be a candidate for or is unwilling to undergo high dose chemotherapy and subsequent stem cell transplant and/or is unable to receive chimeric antigen receptor (CAR) T-cell therapy
* Previous treatment with at least one prior line of systemic therapy (for phase 2, at least 1 and no more than 2 prior lines of systemic therapy). Prior therapy must include an anti-CD20 antibody.
* Adequate bone marrow, hepatic and renal function
* Eastern Cooperative Oncology Group (ECOG) <=2

Exclude criteria

Key Exclusion Criteria:
* Prior treatment with anti-CD47 and/or prior glofitamab or anti-CD20 x CD3 containing regimen. Refractoriness to an obinutuzumab monotherapy containing regimen.
* Prior allogeneic stem cell transplantation or autologous stem cell transplantation within 12 weeks prior to enrolment - Double or triple hit DLBCL lymphoma
* Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection.

Related Information

• Primary Sponsor: Kawai Norisuke
• Secondary ID(s): NCT05896163