Hu5F9-G4 + Rituximab in Relapsed/Refractory B Cell NHL
Research type
Research Study
Full title
A Phase 1b/2 Trial of Hu5F9-G4 in Combination with Rituximab in Patients with Relapsed/Refractory B-cell Non-Hodgkin’s Lymphoma
IRAS ID
211137
Contact name
Graham Collins
Contact email
Sponsor organisation
Forty Seven Inc.
Eudract number
2016-003408-29
Clinicaltrials.gov Identifier
118300, US IND Number
Duration of Study in the UK
1 years, 0 months, 1 days
Research summary
In this research study an investigational drug Hu5F9-G4 is being tested. Hu5F9-G4 is an immunotherapy, consisting of an antibody that targets and blocks a protein called CD47, allowing immune cells to destroy cancer cells. CD47 is an anti-phagocytic “don’t eat me signal”, whereby blockade by Hu5F9-G4 leads to phagocytosis and elimination of tumor cells. Hu5F9-G4 will be administered with the clinically approved anti-CD20 antibody rituximab for non-Hodgkin’s lymphoma. In pre-clinical models, Hu5F9-G4 combination with rituximab led to synergistic anti-tumor activity. Hu5F9-G4 is currently being investigated in patients with solid tumors, lymphomas, and acute myeloid leukemia. Preliminary experience has shown that Hu5F9-G4 has been well-tolerated with the exception of red blood cell elimination, leading to a predictable and transient anemia that is a known consequence of blocking CD47 on red cells. This study will look at the safety and tolerability of Hu5F9-G4 and rituximab administration, the optimal dose of the combination, and anti-tumor efficacy.
Approximately 72 patients will be enrolled in this research study. Patients may continue on the study drug as long as they are tolerating the treatment and the cancer has not progressed or the study is not stopped. Otherwise it is anticipated that this study will take approximately 22 months to complete.
Approximately 16 sites located in the US and United Kingdom will be included in this trial. Additional sites may be included based on enrollment and study timelines.
Lay summary of study results: General information about the study What is NHL?
NHL is a type of blood cancer that affects the lymph nodes, which are tiny, pea-sized organs in the body. These lymph nodes carry B-cells and T-cells or lymphocytes that help the body fight infections. When these cells turn cancerous, they stop fight infections. NHL has 2 main types: indolent NHL (iNHL), which grows slowly, and diffuse large B-cell lymphoma (DLBCL), which is aggressive and spreads quickly.
Existing treatments do not always work well for people with relapsed (cancer that has come back) or refractory (cancer that stops responding to the treatment) iNHL or DLBCL. Therefore, new treatment options are needed for these types of cancers.
Magrolimab is an investigational drug. It is a monoclonal antibody (MAb). MAb are proteins made in a lab to help the body fight diseases like cancer. In this study, researchers assessed the use of magrolimab in combination with other medicines for treating NHL.
What was the purpose of the study?
The purpose of this study was to find a safe dose of magrolimab that can be given with either rituximab (antibody combination) or rituximab-gemcitabine-oxaliplatin (R-GemOx) (chemotherapy combination). Rituximab (R) is also another MAb. Chemotherapy, e.g., GemOx is a combination of medicines that kill cancer cells. The study further assessed the safety and effectiveness of both combinations using a safe and tolerable dose of magrolimab in study participants.
The main questions the researchers wanted to answer in this study were:
• How many participants had dose-limiting toxicities (DLTs) in Phase 1b of the study, if any? DLTs were the side effects that were serious enough to prevent further increase in the dose.
• How many participants had any unwanted medical events (also called Adverse Events (AEs)) during the study? AEs are any unwanted signs or symptoms that participants may have during the study. They may or may not be caused by the study treatment.
• How many participants achieved either complete response (CR) or partial response (PR), known as objective response rate (ORR)? CR means the cancer has completely gone away. PR means there is improvement, but the cancer did not completely go away.
• What side effects did participants have during the study, if any? Side effects are the AEs that the study doctors thought might be caused by the study treatment.
What happened during the study?
The study began in November 2016 and ended in March 2024. The sponsor closed the study earlier than planned, as they decided to stop testing magrolimab for treating blood cancers. This was because magrolimab did not work as expected in other blood cancer studies.
This was an open-label, Phase 1b/2 study. Open label means the participant and the study doctor/study staff knew the treatments the participants were taking.
Phase 1b/2 means the study had 2 phases. Phase 1b, the dose escalation phase, assessed different doses of magrolimab with R or R-GemOx. Phase 2, the dose expansion phase further assessed the effectiveness of the dose of magrolimab deemed safe and tolerable with R or R GemOx in phase 1b. This was done in a larger group of participants with iNHL and DLBCL.
Who took part in the study?
178 participants from the United States, Australia, and the United Kingdom took part in the study.
What treatments did the participants take?
The study treatments, magrolimab, R and R-GemOx were given as a slow injection into a vein in 28-day cycles. A cycle is the interval between the end of one treatment to the start of the next.
Below is the participants’ break-down by each group and the treatments they took in each combination part:
Antibody combination (magrolimab + R) part (145 participants): All participants took an initial dose of magrolimab (1 mg/kg) followed by different maintenance doses, as mentioned below. They also took the same dose of rituximab (375 mg/m2).
Phase 1b (29 participants):
• Group 1 (3 participants): 10 mg/kg maintenance dose
• Group 2 (6 participants): 20 mg/kg maintenance dose
• Group 3 (13 participants): 30 mg/kg maintenance dose along with the same loading dose
• Group 4 (7 participants): 45 mg/kg maintenance dose along with the same loading dose
Phase 2 (116 participants):
• Group 1 (43 participants): 30 mg/kg maintenance dose
• Group 2 (14 participants): 30 mg/kg maintenance dose along with the same loading dose
• Group 3 (31 participants): 45 mg/kg maintenance dose along with the same loading dose
• Group 4 (28 participants): 45 mg/kg maintenance dose
Chemotherapy combination (magrolimab + R-GemOx) part (33 participants):
Phase 1b: All participants took an initial dose of magrolimab (1 mg/kg) followed by different maintenance doses, mentioned below. They also took the same dose of R-GemOx, (R 375 mg/m2, Gem 1000 mg/m2, and Ox 100 mg/m2). The treatment with R-GemOx was given up to 4 or a maximum 8 cycles.
• Group 5 (26 participants): 30 mg/kg as maintenance dose
• Group 6 (7 participants): 45 mg/kg as maintenance dose
What were the results of the study?
This is a summary of the main results from this study.
How many participants had DLTs in Phase 1b of the study, if any?
The results in this section included 28 out of 29 participants in the antibody combination part and 11 out of 33 participants in the chemotherapy combination part.
Below is the summary of participants who had DLTs:
• Phase 1b of the antibody combination: 4 out of 28 participants experienced a DLT at 3 different doses:
- Group 1 (magrolimab 10 mg/kg + R): None
- Group 2 (magrolimab 20 mg/kg + R): 1 out of 6 (17%) participants
- Group 3 (magrolimab 30 mg/kg + R): 2 out of 13 (15%) participants
- Group 4 (magrolimab 45 mg/kg + R): 1 out of 6 (17%) participants
• Phase 1b of chemotherapy combination: Only 1 out of 6 (17%) participants experienced a DLT in Group 6 at magrolimab 45 mg/kg dose + rituximab
How many participants had any unwanted medical events (AEs) during the study?
Most of the study participants had some AEs during the study.
The total number of participants in the Phase 1b and 2 antibody treatment group that experienced AEs were: 144 of 145 (99%) participants.
The total number of participants in the Phase 1b chemotherapy treatment group that experienced AEs was: 32 of 33 (97%) participants.
How many participants achieved either complete response (CR) or partial response (PR), known as objective response rate (ORR)?
The participants were assessed for ORR based on their disease type in the antibody combination part and by each dose in the chemotherapy combination part.
Below is the summary of participants who achieved ORR.
• Phase 1b and Phase 2 antibody combination: In total, 47 out of 145 (32%) participants
- In participants with DLBCL: 23 out of 99 (23%) participants
- In participants with iNHL: 24 out of 46 (52%) participants
• Phase 1b chemotherapy combination: In total, 17 out of 33 (52%) participants
- Group 5 (magrolimab 30 mg/kg + R-GemOx): 12 out of 26 (46%) participants
- Group 6 (magrolimab 45 mg/kg + R-GemOx): 5 out of 7 (71%) participants
What side effects did participants have during the study?
Below is a summary of the side effects for all study participants.
Out of 178 participants, 158 (89%) had side effects, 48 (27%) had serious side effects, and 20 (11%) discontinued the study drug due to side effects.
A side effect is considered “serious” if i) results in death, ii) is life-threatening, iii) is considered by the study doctor to be medically important, iv) causes lasting problems v) requires hospital care, vi) causes a birth defect.
One death occurred in 1 participant in Group 5 (30 mg/kg magrolimab + R-GemOx) chemotherapy group, due to a side effect of swelling (inflammation) and irritation of the large intestine (colitis).
The most common (top 3) serious side effects were:
- Reaction during or following infusion of a drug (infusion-related reaction)
- Low number of red blood cells (anaemia)
- Fever (pyrexia)
The most common (top 3) non-serious side effects were:
- Infusion-related reaction
- Extreme tiredness (fatigue)
- Anaemia
The non-serious side effects were the side effects that were not serious in nature and did not meet the definition of ‘serious side effects’.
There were other serious and non-serious side effects, but those occurred in fewer participants. Some participants may have had more than 1 serious or non-serious side effect.
This summary was created and approved by Gilead Sciences in November 2024. The information in this summary does not include any information available after this date.
Thank you!REC name
London - City & East Research Ethics Committee
REC reference
17/LO/0893
Date of REC Opinion
17 Aug 2017
REC opinion
Further Information Favourable Opinion