CC-99282 + Anti-Lymphoma Agents for Non-Hodgkin's Lymphoma
Recruiting in Palo Alto (17 mi)
+128 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Celgene
Must not be taking: Immunosuppressants, Corticosteroids
Disqualifiers: Life expectancy ≤ 2 months, Cardiac disease, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?
This trial is testing a new drug, CC-99282, for patients with certain types of lymphoma who haven't responded to other treatments. Researchers are finding the safest dose and checking if it works better alone or with other drugs.
Will I have to stop taking my current medications?
The trial does not specify if you must stop taking your current medications, but you cannot have had any systemic anti-cancer treatment within 4 weeks or 5 half-lives before starting the trial. Also, you cannot be on chronic immunosuppressive therapy or corticosteroids.
What data supports the effectiveness of the drug combination CC-99282 and other anti-lymphoma agents for treating non-Hodgkin's lymphoma?
Epcoritamab, a component of the treatment, has shown strong antitumor activity in patients with relapsed or refractory B-cell non-Hodgkin lymphoma, and has received approval for treating diffuse large B-cell lymphoma (DLBCL) after multiple lines of therapy. Additionally, tafasitamab, another component, has demonstrated effectiveness in combination with lenalidomide for relapsed or refractory DLBCL, leading to its approval for patients ineligible for stem cell transplantation.12345
Is the treatment CC-99282 + Anti-Lymphoma Agents generally safe for humans?
Tafasitamab, when used with lenalidomide, has been associated with some adverse events like infections, blood disorders, and gastrointestinal issues, but it was generally well tolerated in patients with diffuse large B-cell lymphoma. Epcoritamab, another component, showed common side effects such as fatigue, nausea, and diarrhea, but was also generally well tolerated in patients with relapsed or refractory large B-cell lymphoma.14567
What makes the drug CC-99282 + Tafasitamab unique for treating non-Hodgkin's lymphoma?
Eligibility Criteria
This trial is for people with Non-Hodgkin's Lymphoma that has come back or hasn't responded to treatment. Participants should be fairly active and able to care for themselves (ECOG status 0-2). They can't join if they're on long-term immune-weakening drugs, have serious heart issues, are expected to live less than 2 months, or recently had cancer treatments.Inclusion Criteria
My Non-Hodgkin's Lymphoma has come back or didn't respond to treatment.
I can take care of myself and am up and about more than half of my waking hours.
Exclusion Criteria
I have heart problems that affect my daily activities.
There are other requirements that you must meet or avoid to participate in the study.
I am on long-term immunosuppressants or have significant GVHD.
See 2 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Dose Escalation
Evaluation of the safety and tolerability of escalating doses of CC-99282 to determine the maximum tolerated dose (MTD) as monotherapy
Variable duration
Dose Expansion
Further evaluation of the safety and preliminary efficacy of CC-99282 alone or in combination with anti-lymphoma agents
Variable duration
Follow-up
Participants are monitored for safety and effectiveness after treatment
Up to approximately 6 years
Treatment Details
Interventions
- CC-99282 (Histone Methyltransferase Inhibitor)
- Obinutuzumab (Monoclonal Antibodies)
- Rituximab (Monoclonal Antibodies)
- Tafasitamab (Monoclonal Antibodies)
- Tazemetostat (Histone Methyltransferase Inhibitor)
Trial OverviewThe study is testing the safety and initial effectiveness of a new drug called CC-99282 alone and combined with other lymphoma medications like Valemetostat, Tafasitamab, Obinutuzumab, and Rituximab in those whose lymphoma has relapsed or isn’t responding to current treatments.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Part B: Dose ExpansionExperimental Treatment5 Interventions
Group II: Part A: Dose EscalationExperimental Treatment1 Intervention
CC-99282 is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Epkinly for:
- Diffuse large B-cell lymphoma
- High-grade B-cell lymphoma
- Follicular lymphoma
🇪🇺 Approved in European Union as Tepkinly for:
- Diffuse large B-cell lymphoma
- High-grade B-cell lymphoma
- Follicular lymphoma
🇨🇦 Approved in Canada as Epkinly/Tepkinly for:
- Diffuse large B-cell lymphoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
McGill University Health Centre MUHCMontreal, Canada
Princess Margaret Cancer CentreToronto, Canada
University Of Kansas Cancer CenterOverland Park, KS
Mayo Clinic in Rochester, MinnesotaRochester, MN
More Trial Locations
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Who Is Running the Clinical Trial?
CelgeneLead Sponsor
References
Tafasitamab: First Approval. [2022]Tafasitamab (tafasitamab-cxix; MONJUVI®) is an Fc-modified (i.e. two amino acid substitutions within the Fc region, resulting in increased Fcγ receptor affinity), humanized, anti-CD19 monoclonal antibody. Developed by MorphoSys AG, under a license from Xencor, it received accelerated approval (in July 2020) for use in combination with lenalidomide as a treatment for adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplantation (ASCT). It is the first therapy to be approved as a second-line treatment for this patient population in the USA. The recommended dose of tafasitamab is 12 mg per kg of bodyweight, administered via an intravenous infusion. A regulatory assessment for tafasitamab plus lenalidomide for the treatment of adults with relapsed or refractory DLBCL is currently underway in the EU. Tafasitamab is also being clinically investigated as a therapeutic option in various other B-cell malignancies, including follicular lymphoma and other indolent non-Hodgkin's lymphoma. This article summarizes the milestones in the development of tafasitamab leading to this first approval for its use in combination with lenalidomide in adults with relapsed or refractory DLBCL.
Dose escalation of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an open-label, phase 1/2 study. [2021]Patients with relapsed or refractory B-cell non-Hodgkin lymphoma have few treatment options. We aimed to establish the safety and recommended phase 2 dose of epcoritamab, a novel bispecific antibody that targets CD3 and CD20 and induces T-cell-mediated cytotoxic activity against CD20+ malignant B cells.
RE-MIND: Comparing Tafasitamab + Lenalidomide (L-MIND) with a Real-world Lenalidomide Monotherapy Cohort in Relapsed or Refractory Diffuse Large B-cell Lymphoma. [2023]Tafasitamab, an Fc-modified, humanized, anti-CD19 monoclonal antibody, in combination with lenalidomide, demonstrated efficacy in transplant-ineligible patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), in the single-arm, phase II L-MIND study (NCT02399085). RE-MIND, a retrospective observational study, generated a historic control for L-MIND to delineate the contribution of tafasitamab to the efficacy of the combination.
Epcoritamab, a Novel, Subcutaneous CD3xCD20 Bispecific T-Cell-Engaging Antibody, in Relapsed or Refractory Large B-Cell Lymphoma: Dose Expansion in a Phase I/II Trial. [2023]Label="PURPOSE">Epcoritamab is a subcutaneously administered CD3xCD20 T-cell-engaging, bispecific antibody that activates T cells, directing them to kill malignant CD20+ B cells. Single-agent epcoritamab previously demonstrated potent antitumor activity in dose escalation across B-cell non-Hodgkin lymphoma subtypes.
Epcoritamab: First Approval. [2023]Epcoritamab (epcoritamab-bysp; Epkinly™; Tepkinly®) is a subcutaneously administered CD3×CD20 T-cell-engaging bispecific antibody being co-developed by Genmab and AbbVie for the treatment of mature B-cell non-Hodgkin lymphoma subtypes (B-NHLs), including diffuse large B-cell lymphoma (DLBCL). Epcoritamab received its first (conditional) approval on 19 May 2023, in the USA, for the treatment of adult patients with relapsed or refractory (R/R) DLBCL, not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma after ≥ 2 lines of systemic therapy. Elsewhere, epcoritamab has received a positive opinion in the EU as a monotherapy for the treatment of adults with R/R DLBCL after ≥ 2 lines of systemic therapy, and is currently under regulatory review in Japan for the treatment of adults with R/R large B-cell lymphoma after ≥ 2 lines of systemic therapy. Clinical development of epcoritamab as monotherapy and in combination with standard of care agents for the treatment of mature B-NHLs is ongoing globally. This article summarizes the milestones in the development of epcoritamab leading to this first approval for R/R DLBCL.
A phase II multicenter study of the anti-CD19 antibody drug conjugate coltuximab ravtansine (SAR3419) in patients with relapsed or refractory diffuse large B-cell lymphoma previously treated with rituximab-based immunotherapy. [2019]This phase II, single-arm, multicenter study examined the efficacy and safety of coltuximab ravtansine (an anti-CD19 antibody drug conjugate) in 61 patients with histologically documented (de novo or transformed) relapsed or refractory diffuse large B-cell lymphoma who had previously received rituximab-containing immuno-chemotherapy. Patients had received a median of 2.0 (range 0-9) prior treatment regimens for diffuse large B-cell lymphoma and almost half (45.9%) had bulky disease (≥1 lesion >5 cm) at trial entry. Patients received coltuximab ravtansine (55 mg/m2) in 4 weekly and 4 biweekly administrations until disease progression or unacceptable toxicity. Forty-one patients were eligible for inclusion in the per protocol population. Overall response rate (International Working Group criteria) in the per protocol population, the primary end point, was 18/41 [43.9%; 90% confidence interval (CI:) 30.6-57.9%]. Median duration of response, progression-free survival, and overall survival (all treated patients) were 4.7 (range 0.0-8.8) months, 4.4 (90%CI: 3.02-5.78) months, and 9.2 (90%CI: 6.57-12.09) months, respectively. Common non-hematologic adverse events included asthenia/fatigue (30%), nausea (23%), and diarrhea (20%). Grade 3-4 adverse events were reported in 23 patients (38%), the most frequent being hepatotoxicity (3%) and abdominal pain (3%). Eye disorders occurred in 15 patients (25%); all were grade 1-2 and none required a dose modification. Coltuximab ravtansine monotherapy was well tolerated and resulted in moderate clinical responses in pre-treated patients with relapsed/refractory diffuse large B-cell lymphoma. (Registered at: clinicaltrials.gov identifier: 01472887).
The European Medicines Agency Review of Tafasitamab in Combination With Lenalidomide for the Treatment of Adult Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma. [2021]Tafasitamab is a humanized monoclonal antibody that binds to the CD19 antigen, which is expressed in tumor cells from patients with diffuse large B-cell lymphoma (DLBCL). On June 24, 2021, a positive opinion for a conditional marketing authorization was issued by the European Medicines Agency (EMA)'s Committee for Medicinal Products for Human Use (CHMP) for tafasitamab, in combination with lenalidomide, for the treatment of adult patients with relapsed or refractory DLBCL who are ineligible for autologous stem cell transplantation. Tafasitamab was evaluated in the phase 2 single-arm, multicenter, open-label L-MIND clinical trial. The primary endpoint of this trial was objective response rate (ORR). The best ORR, achieved at any time during the study, was 56.8% (95% confidence interval: 45.3%-67.8%), and the median duration of response was 34.6 months (95% confidence interval: 26.1-not reached). The most frequently reported adverse events by system organ class were infections and infestations (72.8%; grade ≥3: 29.6%), blood and lymphatic system disorders (65.4%; grade ≥3: 56.8%), gastrointestinal disorders (64.2%; grade ≥3: 2.5%), and general disorders and administration site conditions (58.0%; grade ≥3: 8.6%). The aim of this article is to summarize the scientific review of the application which led to the positive opinion by the CHMP.
Immunotherapeutic approaches for the treatment of childhood, adolescent and young adult non-Hodgkin lymphoma. [2018]With the introduction of the anti-CD20 monoclonal antibody rituximab, B-cell non-Hodgkin lymphoma was the first malignancy successfully treated with an immunotherapeutic agent. Since then, numerous advances have expanded the repertoire of immunotherapeutic agents available for the treatment of a variety of malignancies, including many lymphoma subtypes. These include the introduction of monoclonal antibodies targeting a variety of cell surface proteins, including the successful targeting of immunoregulatory checkpoint receptors present on T-cells or tumour cells. Additionally, cellular immunotherapeutic approaches utilize T- or Natural Killer-cells generated with chimeric antigen receptors against cell surface proteins or Epstein-Barr virus-associated latent membrane proteins. The following review describes the current state of immunotherapy for non-Hodgkin lymphoma including a summary of currently available data and promising agents currently in clinical development with future promise in the treatment of childhood, adolescent and young adult non-Hodgkin lymphoma.
Immunity War: A Novel Therapy for Lymphoma Using T-cell Bispecific Antibodies. [2019]The activity of T-cell-mediated immunotherapies in B-cell lymphoma has been limited to date. The novel bispecific antibody CD20-TCB has a 2:1 antibody design to maximize T-cell engagement and demonstrates activity in preclinical models. This may represent a novel therapeutic approach for patients with relapsed/refractory non-Hodgkin lymphoma (NHL). Clin Cancer Res; 24(19); 4631-2. ©2018 AACR See related article by Bacac et al., p. 4785.
Epcoritamab induces potent anti-tumor activity against malignant B-cells from patients with DLBCL, FL and MCL, irrespective of prior CD20 monoclonal antibody treatment. [2021]Epcoritamab (DuoBody-CD3xCD20, GEN3013) is a novel bispecific IgG1 antibody redirecting T-cells toward CD20+ tumor cells. Here, we assessed the preclinical efficacy of epcoritamab against primary tumor cells present in the lymph node biopsies from newly diagnosed (ND) and relapsed/refractory (RR) B-NHL patients. In the presence of T-cells from a healthy donor, epcoritamab demonstrated potent activity against primary tumor cells, irrespective of prior treatments, including CD20 mAbs. Median lysis of 65, 74, and 84% were achieved in diffuse large B-cell lymphoma (n = 16), follicular lymphoma (n = 15), and mantle cell lymphoma (n = 8), respectively. Furthermore, in this allogeneic setting, we discovered that the capacity of B-cell tumors to activate T-cells was heterogeneous and showed an inverse association with their surface expression levels of the immune checkpoint molecule Herpesvirus Entry Mediator (HVEM). In the autologous setting, when lymph node (LN)-residing T-cells were the only source of effector cells, the epcoritamab-dependent cytotoxicity strongly correlated with local effector cell-to-target cell ratios. Further analyses revealed that LN-residing-derived or peripheral blood-derived T-cells of B-NHL patients, as well as heathy donor T-cells equally mediated epcoritamab-dependent cytotoxicity. These results show the promise of epcoritamab for treatment of newly-diagnosed or relapsed/refractory B-NHL patients, including those who became refractory to previous CD20-directed therapies.