AFM13 + AB-101 for Lymphoma

(LuminICE-203 Trial)

No longer recruiting at 15 trial locations

Overseen By Affimed GmbH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Affimed GmbH

Must be taking: Brentuximab vedotin, PD1 inhibitors

Must not be taking: Therapeutic mAb, Immunosuppressives

Disqualifiers: CNS involvement, Hepatitis B/C, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 7

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments, AFM13 (Acimtamig) and AB-101 (AlloNK), to evaluate their safety and effectiveness for individuals with certain types of lymphoma, particularly those unresponsive to other treatments. The focus is on classical Hodgkin Lymphoma and specific peripheral T-cell lymphomas (PTCL) that express the CD30 protein. Suitable candidates have experienced a recurrence or lack of response to at least two prior treatments, including certain chemotherapy combinations and targeted therapies. As a Phase 2 trial, this research aims to measure the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those who have had recent treatment with certain immunosuppressive medications or therapeutic antibodies. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that AFM13, when used alone, is safe for patients with certain types of lymphoma. In studies combining AFM13 with AB-101, the combination was also well-tolerated. AB-101, a therapy using natural killer cells, has been found safe for patients with non-Hodgkin lymphoma.

These studies suggest that the combination of AFM13 and AB-101 could be safe for people. However, as these treatments are still in the early stages of testing together, ongoing trials are crucial to confirm their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about AFM13 and AB-101 for lymphoma because they offer a novel approach compared to standard treatments like chemotherapy and radiation. AFM13 is an antibody that specifically targets CD30-positive cells, which are often found in Hodgkin lymphoma, allowing for more precise treatment. AB-101 consists of natural killer (NK) cells engineered to enhance the immune system's ability to attack cancer cells. This combination aims to not only directly target cancer cells but also boost the body's immune response, potentially leading to more effective and faster results with fewer side effects than traditional treatments.

What evidence suggests that this trial's treatments could be effective for lymphoma?

Research shows that using AFM13 with AB-101 can enhance the body's ability to fight Hodgkin Lymphoma (HL) and certain types of Peripheral T-Cell Lymphoma (PTCL). In this trial, participants will receive varying doses of the AFM13 and AB-101 combination. Earlier studies demonstrated that AFM13 alone yielded good results, particularly for PTCL patients. When combined with AB-101, it guides immune cells to better target cancer cells. Previous trials showed high success rates, especially in patients who had tried many other treatments. This combination could offer new hope for those with HL and CD30-positive PTCL that have returned or are difficult to treat. ^{1 2 3 6 7}

Who Is on the Research Team?

Wunderle Lydia, MD

Principal Investigator

Affimed Inc.

Are You a Good Fit for This Trial?

This trial is for adults with relapsed or refractory Hodgkin's Lymphoma (HL) or certain types of Peripheral T-Cell Lymphoma (PTCL) that are CD30-positive. Participants must have undergone specific previous treatments, including chemotherapy and possibly stem cell transplants. They cannot join if they've had a solid organ transplant, severe autoimmune disease, another cancer within the last 2 years, active brain metastasis, or untreated HIV/Hepatitis B/C.

Inclusion Criteria

My cancer is active again and shows up on certain scans.

I have had chemotherapy for my T-cell lymphoma or been intolerant to brentuximab if I have the ALCL subtype.

Ability to understand and sign the ICF

Exclusion Criteria

Known active Hepatitis B or C defined per protocol

I have been treated with AFM13 or CBNK cells before.

I have untreated or uncontrolled brain metastasis or positive brain fluid test.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-in

Safety run-in exploring AFM13/AB-101 combination treatment in subjects with classical HL, testing two dose levels in 4 cohorts

48 days per cycle, up to 3 cycles

Visits on Day 1, Day 8, Day 15 of each cycle

Main Study

Evaluation of selected dose levels in a randomized Simon two-stage design for subjects with classical HL

48 days per cycle, up to 3 cycles

Exploratory Cohort

Enrollment of subjects with select CD30-positive PTCL subtypes after completion of the safety run-in

48 days per cycle, up to 3 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 24 months

Tumor assessment every 6 weeks for 3 cycles, then every 3 months for the first 12 months, and every 6 months thereafter

What Are the Treatments Tested in This Trial?

Interventions

• AB-101
• AFM13

Trial Overview The study tests AFM13 combined with AB-101 to evaluate their safety and effectiveness in treating HL and PTCL. It includes an initial safety review followed by expansion cohorts where more participants receive the treatment. The trial involves multiple centers and is open-label, meaning both researchers and participants know what treatment is being given.

How Is the Trial Designed?

Group I: Safety run-in in Hodgkin Lymphoma Experimental Treatment 5 Interventions

4 safety run-in cohorts: * Cohort 1: 200 mg AFM13 + AB-101 (2 × 10e9 cells on Day 1, Day 8, Day 15) * Cohort 2: 300 mg AFM13 + AB-101 (2 × 10e9 cells on Day 1, Day 8, Day 15) * Cohort 3: 200 mg AFM13 + AB-101 (4 × 10e9 cells on Day 1; 2 × 10e9 cells on Day 8, Day 15) * Cohort 4: 300 mg AFM13 + AB-101 (4 × 10e9 cells on Day 1; 2 × 10e9 cells on Day 8, Day 15)

Group II: Exploratory: AFM13 + AB-101 on CD30-positive PTCL Experimental Treatment 5 Interventions

AFM13 + AB-101 on select CD30-positive PTCL subtypes (Dose Level A or B)

Group III: Dose Level B in Hodgkin Lymphoma Experimental Treatment 5 Interventions

Randomized Simon 2-stage design in Hodgkin Lymphoma Dose Level B (selected from cohort 1-4 of Safety run-in)

Group IV: Dose Level A in Hodgkin Lymphoma Experimental Treatment 5 Interventions

Randomized Simon 2-stage design in Hodgkin Lymphoma Dose Level A (selected from cohort 1-4 of Safety run-in)

Who Is Running the Clinical Trial?

Affimed GmbH

Lead Sponsor

Trials

11

Recruited

650+

Artiva Biotherapeutics, Inc.

Industry Sponsor

Trials

6

Recruited

520+

Published Research Related to This Trial

In a study of 24 patients with relapsed or refractory follicular or mantle cell lymphoma, 131 I-rituximab demonstrated significant efficacy, with 9 patients achieving complete response and 8 achieving partial response after treatment.

The treatment showed a median progression-free survival of 5.9 months and overall survival of 37.9 months, although it was associated with common hematologic toxicities, including severe thrombocytopenia and neutropenia in two-thirds of the cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radioimmunotherapy with 131 I-rituximab for patients with relapsed or refractory follicular or mantle cell lymphoma. Jang, YJ., Lim, SM., Lee, I., et al.[2023]

Chimeric antigen receptor (CAR) T cells targeting the immunoglobulin M Fc receptor (FcμR) show promise for treating chronic lymphocytic leukemia (CLL) by selectively eliminating leukemic cells while sparing healthy B cells, unlike traditional CD19-targeting CAR T cells.

In preclinical models, anti-FcμR CAR T cells effectively delayed leukemia progression and demonstrated a superior therapeutic index, suggesting they could offer a safer and more effective treatment option for CLL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cells targeting Fc μ receptor selectively eliminate CLL cells while sparing healthy B cells. Faitschuk, E., Hombach, AA., Frenzel, LP., et al.[2021]

The humanized antibody 1D10 (Hu1D10) shows promise in treating lymphoma, demonstrating superior effectiveness in killing malignant B cells compared to rituxan, particularly when used with blood from patients treated with granulocyte colony-stimulating factor (G-CSF).

Hu1D10 effectively induces apoptosis in primary lymphoma cells from patients with chronic lymphocytic leukaemia, supporting its potential as a therapeutic option and leading to the initiation of a phase I/II clinical trial combining Hu1D10 with G-CSF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced killing of B lymphoma cells by granulocyte colony-stimulating factor-primed effector cells and Hu1D10--a humanized human leucocyte antigen DR antibody. Stockmeyer, B., Schiller, M., Repp, R., et al.[2019]

In a phase 1 study involving 60 patients with relapsed B-cell non-Hodgkin lymphoma, the anti-CD79B antibody-drug conjugate DCDS0780A showed a response rate of 47%, with 28% achieving complete responses, indicating its potential efficacy as a treatment option.

Despite the promising antitumor activity, the study noted significant ocular toxicities at higher doses, which limited dose intensity and suggested that the current TDC format may not expand the therapeutic index for targeting CD79B.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD79B Antibody-Drug Conjugate DCDS0780A in Patients with B-Cell Non-Hodgkin Lymphoma: Phase 1 Dose-Escalation Study. Herrera, AF., Patel, MR., Burke, JM., et al.[2023]

In a study of 56 patients with relapsed/refractory follicular lymphoma, obinutuzumab combined with chemotherapy (either G-CHOP or G-FC) resulted in high response rates of 93% to 96%, indicating strong efficacy for this treatment approach.

The safety profile was acceptable, with most adverse events being mild infusion-related reactions; however, G-FC was associated with more adverse events compared to G-CHOP, suggesting that while both regimens are effective, G-CHOP may be better tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obinutuzumab (GA101) plus CHOP or FC in relapsed/refractory follicular lymphoma: results of the GAUDI study (BO21000). Radford, J., Davies, A., Cartron, G., et al.[2022]

AFM13 is a well-tolerated bispecific antibody that effectively recruits natural killer (NK) cells to target CD30-expressing Hodgkin lymphoma, showing a safety profile with mild to moderate adverse events and no maximum tolerated dose reached in a phase 1 study involving 28 heavily pretreated patients.

The treatment demonstrated promising antitumor activity, with a 23% overall response rate and a 61.5% disease control rate, particularly in patients who were refractory to other treatments, indicating its potential as an effective immunotherapy for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13 in patients with relapsed or refractory Hodgkin lymphoma. Rothe, A., Sasse, S., Topp, MS., et al.[2022]

The humanized IgG4 anti-HLA-DR monoclonal antibody IMMU-114 effectively targets and induces cytotoxicity in various leukemia and lymphoma cell lines, as well as chronic lymphocytic leukemia (CLL) patient specimens, demonstrating its potential as a treatment option.

IMMU-114's mechanism of action involves the activation of ERK and JNK signaling pathways, which is crucial for its cytotoxic effects, distinguishing it from other monoclonal antibodies like those targeting CD20 and CD74.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapy of B-cell malignancies by anti-HLA-DR humanized monoclonal antibody, IMMU-114, is mediated through hyperactivation of ERK and JNK MAP kinase signaling pathways. Stein, R., Gupta, P., Chen, X., et al.[2021]

CMC-544, a CD22-targeted immunoconjugate, significantly extended the survival of mice with disseminated B-cell lymphoma, with some mice considered cured after treatment, demonstrating its potent antitumor efficacy.

The treatment was effective even when administered up to 15 days after the onset of the disease, unlike other control treatments, indicating its potential for use in both early and late stages of B-cell lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potent and specific antitumor efficacy of CMC-544, a CD22-targeted immunoconjugate of calicheamicin, against systemically disseminated B-cell lymphoma. DiJoseph, JF., Goad, ME., Dougher, MM., et al.[2019]

The chimeric anti-CD20 monoclonal antibody IBI301 was well tolerated in nine Chinese patients with CD20(+) B-cell non-Hodgkin's lymphoma, with no severe adverse events or dose-limiting toxicities reported during the study.

IBI301 effectively eliminated peripheral CD20-expressing B cells in all patients, indicating its potential efficacy in targeting B-cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Tolerance and pharmacodynamics phase Ⅰ clinical trial study of chimeric anti-CD20 monoclonal antibody IBI301 in Chinese patients with CD20-positive non-Hodgkin's lymphoma]. Jiang, B., Qi, JY., Sun, MY., et al.[2020]

T cells from B-cell lymphoma patients show reduced numbers and functionality after certain chemotherapy regimens, which can impact the effectiveness of the bispecific antibody AFM11, currently in phase I trials for treating non-Hodgkin lymphoma and acute lymphoblastic leukemia.

Despite the reduced T-cell functionality, AFM11 was still able to activate T-cell immunity against B cells in all treatment groups, indicating its potential as a treatment option even after chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functionally Defective T Cells After Chemotherapy of B-Cell Malignancies Can Be Activated by the Tetravalent Bispecific CD19/CD3 Antibody AFM11. Duell, J., Lukic, DS., Karg, M., et al.[2020]

Citations

1. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/4855/500870/AFM13-in-Combination-with-Allogeneic-Natural

AFM13 in Combination with Allogeneic Natural Killer Cells ... Combining AFM13 with AB-101 has the potential to synergistically enhance and redirect antitumor immune responses to target HL and CD30 + PTCL cells.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11701429/

A Phase II Study of Acimtamig (AFM13) in Patients with CD30 ... In the presented study, acimtamig monotherapy has exhibited promising efficacy and safety in patients with R/R PTCL. Subgroup analyses revealed pronounced ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05883449

NCT05883449 | Phase 2 Study of AFM13 in Combination ... The study is evaluating the safety and efficacy of AFM13 in combination with AB-101 in subjects with R/R classical HL and CD30-positive PTCL. Detailed ...

4. affimed.com affimed.com/wp-content/uploads/ASH-2023_4855-Moskowitz_AFM13-LuminICE-203-TIP-Poster_10-Nov.pdf

AFM13 in Combination with Allogeneic Natural Killer Cells ... The LuminICE-203 study will establish whether the combination of acimtamig and. AlloNK leads to improved response rates for patients with CD30+ ...

5. onclive.com onclive.com/view/acimtamig-plus-allonk-elicits-responses-in-heavily-pretreated-r-r-hodgkin-lymphoma

Acimtamig Plus AlloNK Elicits Responses in Heavily ... Acimtamig plus AlloNK was associated with high objective response rates in heavily pretreated patients with relapsed/refractory Hodgkin ...

6. bloodcancerunited.org bloodcancerunited.org/resources/newsroom/affimed-announces-ind-clearance-phase-2-clinical-trial-investigating-afm13-and-ab-101

Affimed Announces IND Clearance for a Phase 2 Clinical ... The study will evaluate the safety and efficacy of AFM13 in combination with AB-101 in patients with r/r cHL and CD30-positive PTCL. Affimed intends to ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S000649712311456X

AFM13 in Combination with Allogeneic Natural Killer Cells ... Combining AFM13 with AB-101 has the potential to synergistically enhance and redirect antitumor immune responses to target HL and CD30 + PTCL cells.