AFM13 + AB-101 for Lymphoma
(LuminICE-203 Trial)
Recruiting in Palo Alto (17 mi)
+14 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
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
Prior Safety Data
Trial Summary
What is the purpose of this trial?
AFM13-203 is a phase 2, open-label, multi-center, multi-cohort study with a safety run-in followed by expansion cohorts. 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.
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 the AFM13 treatment safe for humans?
What makes the AFM13 + AB-101 treatment for lymphoma unique?
The AFM13 + AB-101 treatment is unique because it combines AFM13, a bispecific antibody that targets CD30 on lymphoma cells, with AB-101, a type of natural killer (NK) cell therapy. This combination aims to enhance the immune system's ability to attack and destroy lymphoma cells, offering a novel approach compared to traditional chemotherapy or single-agent therapies.678910
Eligibility Criteria
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
See 3 more
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.
See 5 more
Trial Timeline
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
Treatment Details
Interventions
- AB-101 (Monoclonal Antibodies)
- AFM13 (Monoclonal Antibodies)
Trial OverviewThe 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.
Participant Groups
4Treatment groups
Experimental Treatment
Group I: Safety run-in in Hodgkin LymphomaExperimental Treatment5 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 PTCLExperimental Treatment5 Interventions
AFM13 + AB-101 on select CD30-positive PTCL subtypes (Dose Level A or B)
Group III: Dose Level B in Hodgkin LymphomaExperimental Treatment5 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 LymphomaExperimental Treatment5 Interventions
Randomized Simon 2-stage design in Hodgkin Lymphoma Dose Level A (selected from cohort 1-4 of Safety run-in)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Pennsylvania, Abramson Cancer CenterPhiladelphia, PA
UC Irvine HealthOrange, CA
John Theurer Cancer CenterHackensack, NJ
Sarah Cannon Research InstituteDenver, CO
More Trial Locations
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Who Is Running the Clinical Trial?
Affimed GmbHLead Sponsor
Artiva Biotherapeutics, Inc.Industry Sponsor
References
A phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13 in patients with relapsed or refractory Hodgkin lymphoma. [2022]AFM13 is a bispecific, tetravalent chimeric antibody construct (TandAb) designed for the treatment of CD30-expressing malignancies. AFM13 recruits natural killer (NK) cells via binding to CD16A as immune effector cells. In this phase 1 dose-escalation study, 28 patients with heavily pretreated relapsed or refractory Hodgkin lymphoma received AFM13 at doses of 0.01 to 7 mg/kg body weight. Primary objectives were safety and tolerability. Secondary objectives included pharmacokinetics, antitumor activity, and pharmacodynamics. Adverse events were generally mild to moderate. The maximum tolerated dose was not reached. Pharmacokinetics assessment revealed a half-life of up to 19 hours. Three of 26 evaluable patients achieved partial remission (11.5%) and 13 patients achieved stable disease (50%), with an overall disease control rate of 61.5%. AFM13 was also active in brentuximab vedotin-refractory patients. In 13 patients who received doses of ≥1.5 mg/kg AFM13, the overall response rate was 23% and the disease control rate was 77%. AFM13 treatment resulted in a significant NK-cell activation and a decrease of soluble CD30 in peripheral blood. In conclusion, AFM13 represents a well-tolerated, safe, and active targeted immunotherapy of Hodgkin lymphoma. A phase 2 study is currently planned to optimize the dosing schedule in order to further improve the therapeutic efficacy. This phase 1 study was registered at www.clinicaltrials.gov as #NCT01221571.
[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]. [2020]Objective: To evaluate the tolerance and safety of a human-mouse chimeric anti-CD20 monoclonal antibody IBI301 in Chinese patients achieved objective response with CD20(+) B-cell non-Hodgkin's lymphoma (NHL). Methods: Nine patients with CD20(+) B-cell NHL received dose-escalating IBI301 infusions (250 mg/m(2), n=3; 375 mg/m(2), n=3; 500 mg/m(2), n=3, respectively). The data of all patients were collected for safety analyses. The median exposures of 125 mg/m(2), 375 mg/m(2), 500 mg/m(2) dose groups were 243, 690 and 980 mg, respectively. Safety and tolerability were evaluated by monitoring adverse events (AE). The ratios of CD19(+), CD20(+) B cells and the levels IgG and IgM were detected to evaluate the pharmacodynamics. Results: Totally 52 events of AE were observed, including 18 events of AE in 125 mg/m(2) group, 14 events of AE in 375 mg/m(2) group and 20 events of AE in 500 mg/m(2) group, respectively. There were 26 adverse reactions of 52 cases of AE, 22 reactions were judged to be probably related to IBI301, and 4 reactions were not probably related to IBI301, all disappeared or returned to baseline levels. Common AE in this study included decreased WBC, upper respiratory infection, decreased neutrophil count, dyspepsia, hyperuricemia, paresthesia, oral mucositis and dizziness. No patients quitted or trial discontinued. No severe AE (SAE) were reported. No dose-limiting toxicity (DLT) events were observed in the study. The ratio of CD20(+) and CD19(+) B cells decreased in all subjects. There was no significant changes of the levels of IgG and IgM. Conclusions: The single dose of IBI301 injection was well tolerated, and the AE occurred in the patients recovered. No SAE were reported, No DLT events were observed in the study. The IBI301 caused an elimination of the peripheral CD20-expressing B cells in all patients. Clinical trial registration: Chinadrugtrials, CTR20140762.
Obinutuzumab (GA101) plus CHOP or FC in relapsed/refractory follicular lymphoma: results of the GAUDI study (BO21000). [2022]The safety and activity of obinutuzumab (GA101) plus chemotherapy in relapsed/refractory follicular lymphoma was explored in 56 patients. Participants received obinutuzumab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (G-CHOP; every 3 weeks for 6 to 8 cycles) or obinutuzumab plus fludarabine and cyclophosphamide (G-FC; every 4 weeks for 4 to 6 cycles). Patients were randomly assigned to either obinutuzumab 1600 mg on days 1 and 8 of cycle 1 followed by 800 mg on day 1 of subsequent cycles or 400 mg for all doses. Treatment responders were eligible for obinutuzumab maintenance every 3 months for up to 2 years. Grade 1/2 infusion-related reactions (IRRs) were the most common treatment-related adverse event (AE) (all grades: G-CHOP, 68%; G-FC, 82%). Grade 3/4 IRRs were rare (7%) and restricted to the first infusion. All patients received the planned obinutuzumab dose. Neutropenia was the most common treatment-related hematologic AE for G-CHOP (43%) and G-FC (50%). At induction end, 96% (27/28) of patients receiving G-CHOP (complete response [CR], 39% [11/28]) and 93% (26/28) receiving G-FC (CR, 50% [14 of 28]) achieved responses. G-CHOP and G-FC had an acceptable safety profile with no new or unexpected AEs, but G-FC was associated with more AEs than G-CHOP. Obinutuzumab plus chemotherapy resulted in 93% to 96% response rates, supporting phase 3 investigation. This trial was registered at www.clinicaltrials.gov as #NCT00825149.
Radioimmunotherapy with 131 I-rituximab for patients with relapsed or refractory follicular or mantle cell lymphoma. [2023]Label="AIM" NlmCategory="OBJECTIVE">This study aimed to evaluate the safety and efficacy of 131 I-rituximab in patients with relapsed or refractory follicular or mantle cell lymphoma.
Functionally Defective T Cells After Chemotherapy of B-Cell Malignancies Can Be Activated by the Tetravalent Bispecific CD19/CD3 Antibody AFM11. [2020]Immunotherapy of B-cell malignancies with bispecific antibodies is an emerging treatment option. However, not all patients benefit from these therapies, presumably due to pretreatment regimens. Therefore, we determined the effect of different treatment lines on the activity of T cells and their responsiveness to AFM11. AFM11 is a tetravalent, bispecific CD19/CD3 immunoengager based on Affimed's ROCK platform, currently being investigated in phase I clinical trials for non-Hodgkin lymphoma and acute lymphoblastic leukemia. T cells from B-cell lymphoma patients treated with either rituximab+bendamustine (R-Benda), rituximab+CHOP (R-CHOP), or with high-dose BEAM chemotherapy (HD-BEAM) and autologous HSCT were compared with T cells from healthy donors. Overall, in these patients, T-cell numbers were significantly reduced. To determine whether distinct chemotherapy affects AFM11 efficacy, functional T-cell assays were performed. It is interesting to note that, only in assays that combine target cell lysis, cytokine production and proliferation over 4 days at an effector to target ratio of up to 1:25 significant differences could be detected between the different treatment groups: T cells after R-CHOP showed only modest decrease in their functionality when compared with healthy controls, whereas R-Benda and HD-BEAM had a profound effect on AFM11-induced T-cell cytotoxicity. In conclusion, T cells from lymphoma patients are reduced in number and have functional defects following treatment with certain chemotherapy regimens, also reducing AFM11 efficacy. Importantly, AFM11 was still able to trigger B-cell-directed T-cell immunity in all treatment groups.
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. [2021]A humanized IgG4 anti-HLA-DR monoclonal antibody (IMMU-114), engineered to avoid side effects associated with complement activation, was examined for binding and cytotoxicity on leukemia, lymphoma, and multiple myeloma cell lines and chronic lymphocytic leukemia (CLL) patient specimens, followed by evaluation of the effects of IMMU-114 on extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathways. HLA-DR was expressed on the majority of these cells at markedly higher levels than CD20, CD22, and CD74. IMMU-114 was toxic to mantle cell lymphoma, CLL, acute lymphoblastic leukemia, hairy cell leukemia, non-Hodgkin lymphoma (including rituximab-resistant), and multiple myeloma cell lines, and also patient CLL cells. IMMU-114 induced disease-free survival in tumor-bearing SCID mice with early-stage disease and in models that are relatively resistant to anti-CD20 monoclonal antibodies. Despite positive staining, acute myelogenous leukemic cells were not killed by IMMU-114. The ability of IMMU-114 to induce activation of ERK and JNK signaling correlated with cytotoxicity and differentiates the mechanism of action of IMMU-114 from monoclonal antibodies against CD20 and CD74. Thus, antigen expression is not sufficient for cytotoxicity; antibody-induced hyperactivation of ERK and JNK mitogen activated protein kinase signaling pathways are also required.
Chimeric antigen receptor T cells targeting Fc μ receptor selectively eliminate CLL cells while sparing healthy B cells. [2021]Adoptive cell therapy of chronic lymphocytic leukemia (CLL) with chimeric antigen receptor (CAR)-modified T cells targeting CD19 induced lasting remission of this refractory disease in a number of patients. However, the treatment is associated with prolonged "on-target off-tumor" toxicities due to the targeted elimination of healthy B cells demanding more selectivity in targeting CLL cells. We identified the immunoglobulin M Fc receptor (FcμR), also known as the Fas apoptotic inhibitory molecule-3 or TOSO, as a target for a more selective treatment of CLL by CAR T cells. FcμR is highly and consistently expressed by CLL cells; only minor levels are detected on healthy B cells or other hematopoietic cells. T cells with a CAR specific for FcμR efficiently responded toward CLL cells, released a panel of proinflammatory cytokines and lytic factors, like soluble FasL and granzyme B, and eliminated the leukemic cells. In contrast to CD19 CAR T cells, anti-FcμR CAR T cells did not attack healthy B cells. T cells with anti-FcμR CAR delayed outgrowth of Mec-1-induced leukemia in a xenograft mouse model. T cells from CLL patients in various stages of the disease, modified by the anti-FcμR CAR, purged their autologous CLL cells in vitro without reducing the number of healthy B cells, which is the case with anti-CD19 CAR T cells. Compared with the currently used therapies, the data strongly imply a superior therapeutic index of anti-FcμR CAR T cells for the treatment of CLL.
Enhanced killing of B lymphoma cells by granulocyte colony-stimulating factor-primed effector cells and Hu1D10--a humanized human leucocyte antigen DR antibody. [2019]Antibody-based approaches have become a novel treatment modality for lymphoma patients. Humanized 1D10 (Hu1D10; Remitogen) is among the antibodies that are currently under evaluation in phase II clinical trials in lymphoma patients. The 1D10 antibody is directed against a polymorphic epitope on the beta-chain of human leucocyte antigen (HLA) class II. We found expression of the 1D10 epitope on B cells and monocytes from approximately 50% of healthy donors. Analyses of 1D10 expression on malignant cells revealed that approximately half of the HLA class II-positive haematological malignancies expressed the 1D10 epitope. In whole blood antibody-dependent cellular cytotoxicity (ADCC) assays, Hu1D10 was more effective than rituxan in killing malignant ARH-77 B cells. Interestingly, Hu1D10-mediated lymphoma cell lysis was significantly enhanced when blood from granulocyte colony-stimulating factor (G-CSF)-treated patients was compared with blood from healthy controls. Analyses of the relevant effector cell populations revealed that FcgammaRI (CD64)-positive polymorphonuclear cells were critical for enhanced Hu1D10-mediated lymphoma killing during G-CSF therapy, while the same effector cell population induced only marginal lysis with rituxan. Furthermore, Hu1D10 was highly effective in inducing apoptosis in primary lymphoma cells from B chronic lymphocytic leukaemia patients. These preclinical results form the basis for a phase I/II clinical trial of Hu1D10 in combination with G-CSF.
Potent and specific antitumor efficacy of CMC-544, a CD22-targeted immunoconjugate of calicheamicin, against systemically disseminated B-cell lymphoma. [2019]CMC-544 is a CD22-targeted immunoconjugate of calicheamicin and exerts a potent cytotoxic effect against CD22+ B-cell lymphoma. This study evaluated antitumor efficacy of CMC-544 against systemically disseminated B-cell lymphoma.
Anti-CD79B Antibody-Drug Conjugate DCDS0780A in Patients with B-Cell Non-Hodgkin Lymphoma: Phase 1 Dose-Escalation Study. [2023]Targeting CD79B using antibody-drug conjugates (ADC) is an effective therapeutic strategy in B-cell non-Hodgkin lymphoma (B-NHL). We investigated DCDS0780A, an anti-CD79B ADC with THIOMAB technology (TDC) that consistently conjugates two anti-neoplastic molecules per antibody, in contrast with ADCs with heterogeneous loads.