QXL138AM for Multiple Myeloma
Recruiting in Palo Alto (17 mi)
+7 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Nammi Therapeutics Inc
Must not be taking: QT prolonging drugs
Disqualifiers: Cardiac disease, Infections, Liver disease, others
No Placebo Group
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?
Study QXL138AM-001 is a Phase 1a/1b study to investigate the safety, pharmacokinetics, and preliminary activity of QXL138AM in subjects with locally advanced un-resectable and/or metastatic solid tumors and multiple myeloma. The study is an open-label, multicenter, first in human study to be conducted in two major parts which are further organized into two sub-parts. Part A Dose Escalation is a modified 3+3 with the first two cohorts consisting of one subject each based on the low clinical starting dose. Dose escalation in solid tumors (Part A1) will be followed by dose finding in multiple myeloma (Part A2). Part B consists of dose expansion in solid tumors (Part B1) and multiple myeloma (Part B2) using the recommended dose for expansion from Part A
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 use medications that significantly prolong the QT/QTc interval or chronic systemic corticosteroids over 20 mg/day of prednisone. You also need to stop any anticancer therapy at least 28 days before starting the trial.
What data supports the effectiveness of the drug QXL138AM for treating multiple myeloma?
The research highlights the potential of immunotherapy in treating multiple myeloma, with various strategies showing promise in improving patient outcomes. Although not directly about QXL138AM, similar treatments like bispecific antibodies and antibody-drug conjugates have demonstrated effectiveness in targeting and killing myeloma cells, suggesting that QXL138AM may also be effective.12345
What makes the drug QXL138AM unique for treating multiple myeloma?
QXL138AM is unique because it combines an antibody that specifically targets CD138, a protein found on myeloma cells, with interferon alpha 2a, a substance that can boost the immune system's ability to fight cancer. This targeted approach aims to enhance the drug's effectiveness against myeloma cells while potentially reducing side effects compared to traditional interferon treatments.12678
Eligibility Criteria
This trial is for adults with advanced solid tumors or multiple myeloma that can't be removed by surgery or have spread. Participants must have measurable disease and acceptable organ function. They should not be receiving other cancer treatments, and they need to follow specific contraceptive guidelines.Inclusion Criteria
I am a man who can father children and will use effective birth control during and for 4 months after the study.
I have Multiple Myeloma and standard treatments haven't worked for me.
I have at least one tumor that can be measured or my multiple myeloma can be evaluated.
See 6 more
Exclusion Criteria
My mood disorder is not controlled despite treatment in the last 2 years.
My autoimmune disorder is not under control despite treatment.
I am currently breastfeeding.
See 11 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Dose Escalation in Solid Tumors
Dose escalation using a 3+3 design in participants with advanced solid tumors to determine the maximum tolerated dose (MTD) or recommended dose for expansion (RDE-ST).
Variable, until MTD or RDE-ST is determined
Multiple visits for dose administration and monitoring
Dose Escalation in Multiple Myeloma
Dose escalation using a 3+3 design in participants with multiple myeloma to determine the recommended dose for expansion (RDE-MM).
Variable, until RDE-MM is determined
Multiple visits for dose administration and monitoring
Dose Expansion in Solid Tumors
Dose expansion to further explore safety and anti-tumor activity in solid tumors using the RDE-ST.
Anticipated 1.5 years
Regular visits for treatment and monitoring
Dose Expansion in Multiple Myeloma
Dose expansion to further explore safety and anti-tumor activity in multiple myeloma using the RDE-MM.
Anticipated 1.5 years
Regular visits for treatment and monitoring
Follow-up
Participants are monitored for safety and effectiveness after treatment.
4 weeks
Treatment Details
Interventions
- QXL138AM (Monoclonal Antibodies)
Trial OverviewThe study tests QXL138AM, a new drug given as an injection every two weeks. It's in early testing (Phase 1) to see how safe it is, how the body processes it, and if it works against various cancers including kidney, lung, liver, bladder, prostate, ovarian, gastrointestinal cancers and more.
Participant Groups
4Treatment groups
Experimental Treatment
Group I: Phase 1b Dose Expansion in Solid Tumors - Part B1Experimental Treatment1 Intervention
Dose expansion in solid tumors using the recommended dose for expansion from Part A1
Group II: Phase 1b Dose Expansion in Multiple Myeloma - Part B2Experimental Treatment1 Intervention
Dose expansion in Multiple Myeloma using the recommended dose for expansion from Part A2
Group III: Phase 1a Dose Escalation in Solid Tumors - Part A1Experimental Treatment1 Intervention
Dose escalation of QXL138AM in participants with locally advanced un-resectable and/or metastatic solid tumors.
Group IV: Phase 1a Dose Escalation in Multiple Myeloma - Part A2Experimental Treatment1 Intervention
Dose escalation of QXL138AM in participants with multiple myeloma.
QXL138AM is already approved in United States for the following indications:
🇺🇸 Approved in United States as QXL138AM for:
- Orphan Drug Designation for Pancreatic Cancer
- Orphan Drug Designation for Multiple Myeloma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Sarah Cannon Research Institute - Denver DDUDenver, CO
University of Rochester - Wilmot Cancer InstituteRochester, NY
University of Southern CaliforniaLos Angeles, CA
Cedars-Sanai Medical Center - Samuel Oschin Comprehensive CancerLos Angeles, CA
More Trial Locations
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Who Is Running the Clinical Trial?
Nammi Therapeutics IncLead Sponsor
References
BCMA-targeting Bispecific Antibody That Simultaneously Stimulates NKG2D-enhanced Efficacy Against Multiple Myeloma. [2021]B-cell maturation antigen (BCMA) is a highly plasma cell-selective protein expressed on malignant plasma cells of patients with multiple myeloma (MM), and it is a defined therapeutic target. Major histocompatibility complex class I-related chain A (MICA) is frequently expressed in lymphoproliferative malignancies including MM. MICA activates natural killer (NK) cells and costimulates T cells by interaction with its immunoreceptor NK cell receptor G2D (NKG2D). Nonetheless, during full-blown MM, tumor cells promote efficient MICA shedding, which evokes NKG2D internalization and immune suppression. To enhance the directional killing efficacy of immune cells against myeloma cells, we constructed a novel bispecific antibody 2A9-MICA and explored its potential antimyeloma activity against MM. 2A9-MICA consists of human MICA extracellular region and a single-chain antibody fragment (scFv) that targets BCMA generated by phage display technology. In vitro, 2A9-MICA activated NK cell-mediated cytotoxicity and induced NK cells to kill BCMA-positive human myeloma cells. Moreover, in BCMA-positive, MM-bearing nude mice, 2A9-MICA specifically targeted tumor tissue, where it effectively recruited immune cells and inhibited tumor tissue growth showed superior antitumor activity. Taken together, bispecific antibody 2A9-MICA provides a new approach for MM-targeting immunotherapy and has attractive potential for clinical applications.
Generation of monoclonal antibodies to surface proteins of human multiple myeloma employing membrane extracts for murine in vivo immunizations. [2009]Multiple myeloma is a malignancy of plasma cells that accounts for 1% of cancers worldwide and is treatable, yet incurable. U266 is an IgE-secreting, IL-6-producing human multiple myeloma cell line, against whose unique surface markers we have tried to raise monoclonal antibodies (MAbs). Female Balb/c mice (6 weeks old) were immunized through two routes of administration, with three different antigenic concentrations. Fusion efficiencies and specific efficiencies for the three antigenic concentrations were calculated. It was found that while an initial immunogen concentration of 10 microg gave the best fusion efficiency of 63.89%, an initial immunogen concentration of 15 microg resulted in the best specific efficiency of 54.54%. Out of the 147 supernatants selected for screening, 66 were found reactive to common surface proteins of non-malignant human plasma cells and seven were myeloma-specific MAbs. These MAbs have a range of potential applications in multiple myeloma imaging, phenotyping, and possible targeted therapy.
Keeping Myeloma in Check: The Past, Present and Future of Immunotherapy in Multiple Myeloma. [2023]Multiple myeloma is an incurable disease of malignant plasma cells and an ideal target for modern immune therapy. The unique plasma cell biology maintained in multiple myeloma, coupled with its hematological nature and unique bone marrow microenvironment, provide an opportunity to design specifically targeted immunotherapies that selectively kill transformed cells with limited on-target off-tumor effects. Broadly defined, immune therapy is the utilization of the immune system and immune agents to treat a disease. In the context of multiple myeloma, immune therapy can be subdivided into four main categories: immune modulatory imide drugs, targeted antibodies, adoptive cell transfer therapies, and vaccines. In recent years, advances in all four of these categories have led to improved therapies with enhanced antitumor activity and specificity. In IMiDs, modified chemical structures have been developed that improve drug potency while reducing dose limiting side effects. Targeted antibody therapies have resulted from the development of new selectively expressed targets as well as the development of antibody drug conjugates and bispecific antibodies. Adoptive cell therapies, particularly CAR-T therapies, have been enhanced through improvements in the manufacturing process, as well as through the development of CAR constructs that enhance CAR-T activation and provide protection from a suppressive immune microenvironment. This review will first cover in-class breakthrough therapies for each of these categories, as well as therapies currently utilized in the clinic. Additionally, this review will explore up and coming therapeutics in the preclinical and clinical trial stage.
New Strategies in Multiple Myeloma: Immunotherapy as a Novel Approach to Treat Patients with Multiple Myeloma. [2018]Multiple myeloma is a B-cell malignancy characterized by proliferation of monoclonal plasma cells in the bone marrow. Although new therapeutic options introduced in recent years have resulted in improved survival outcomes, multiple myeloma remains incurable for a large number of patients, and new treatment options are urgently needed. Over the last 5 years, there has been a renewed interest in the clinical potential of immunotherapy for the treatment of multiple myeloma. Clinical progression of myeloma is known to be associated with progressive immune dysregulation and loss of immune surveillance that contribute to disease progression in association with progressive genetic complexity, rendering signaling-based treatments less effective. A variety of strategies to reverse the multiple myeloma-induced immunosuppression has been developed either in the form of immunomodulatory drugs, checkpoint inhibitors, mAbs, engineered T cells, and vaccines. They have shown encouraging results in patients with relapsed refractory multiple myeloma and hold great promise in further improving patient outcomes in multiple myeloma. This review will summarize the major approaches in multiple myeloma immunotherapies and discuss the mechanisms of action and clinical activity of these strategies. Clin Cancer Res; 22(24); 5959-65. ©2016 AACR.
Novel anti-B-cell maturation antigen antibody-drug conjugate (GSK2857916) selectively induces killing of multiple myeloma. [2023]B-cell maturation antigen (BCMA), highly expressed on malignant plasma cells in human multiple myeloma (MM), has not been effectively targeted with therapeutic monoclonal antibodies. We here show that BCMA is universally expressed on the MM cell surface and determine specific anti-MM activity of J6M0-mcMMAF (GSK2857916), a novel humanized and afucosylated antagonistic anti-BCMA antibody-drug conjugate via a noncleavable linker. J6M0-mcMMAF specifically blocks cell growth via G2/M arrest and induces caspase 3-dependent apoptosis in MM cells, alone and in coculture with bone marrow stromal cells or various effector cells. It strongly inhibits colony formation by MM cells while sparing surrounding BCMA-negative normal cells. J6M0-mcMMAF significantly induces effector cell-mediated lysis against allogeneic or autologous patient MM cells, with increased potency and efficacy compared with the wild-type J6M0 without Fc enhancement. The antibody-dependent cell-mediated cytotoxicity and apoptotic activity of J6M0-mcMMAF is further enhanced by lenalidomide. Importantly, J6M0-mcMMAF rapidly eliminates myeloma cells in subcutaneous and disseminated mouse models, and mice remain tumor-free up to 3.5 months. Furthermore, J6M0-mcMMAF recruits macrophages and mediates antibody-dependent cellular phagocytosis of MM cells. Together, these results demonstrate that GSK2857916 has potent and selective anti-MM activities via multiple cytotoxic mechanisms, providing a promising next-generation immunotherapeutic in this cancer.
A sequential cohort study evaluating single-agent KappaMab and KappaMab combined with lenalidomide and low-dose dexamethasone in relapsed and/or refractory kappa light chain-restricted multiple myeloma (AMaRC 01-16). [2023]KappaMab (KM; formerly MDX-1097) is a monoclonal antibody specific for the kappa myeloma antigen (KMA), a cell-surface antigen expressed on malignant plasma cells in kappa-restricted multiple myeloma (κMM), some lymphomas, occasional tonsillar B cells and in vitro activated B cells, but not on normal B cells in bone marrow. Phase I/IIa studies of single-agent KM confirmed a favourable toxicity profile and evidence of anti-myeloma activity. Ex-vivo studies demonstrating upregulation of KMA by lenalidomide, and enhanced effector-cell cytotoxicity provided the rationale for this phase IIb study where KM or KM in combination with lenalidomide and dexamethasone (KM-Rd) was administered in relapsed, refractory κMM patients. In addition, outcomes for a real-world matched case-control cohort from the Australian and New Zealand Myeloma and Related Diseases Registry (MRDR) who received Rd were compared to the KM-Rd cohort. KM-Rd demonstrated an overall response rate of 82.5% which compared favourably to the Rd-MRDR cohort of 45.1%. Both single-agent KM and KM-Rd regimens were well tolerated, with the KM-Rd safety profile similar to patients given only Rd in other clinical settings. Based on the excellent safety profile and significant efficacy, further clinical trials escalating the KM dose and pairing KM with other standard-of-care treatments are planned.
Development of a Targeted Mass-Spectrometry Serum Assay To Quantify M-Protein in the Presence of Therapeutic Monoclonal Antibodies. [2018]M-protein diagnostics can be compromised for patients receiving therapeutic monoclonal antibodies as treatment in multiple myeloma. Conventional techniques are often not able to distinguish between M-proteins and therapeutic monoclonal antibodies administered to the patient. This may prevent correct response assessment and can lead to overtreatment. We have developed a serum-based targeted mass-spectrometry assay to detect M-proteins, even in the presence of three therapeutic monoclonal antibodies (daratumumab, ipilimumab, and nivolumab). This assay can target proteotypic M-protein peptides as well as unique peptides derived from therapeutic monoclonal antibodies. We address the sensitivity in M-protein diagnostics and show that our mass-spectrometry assay is more than two orders of magnitude more sensitive than conventional M-protein diagnostics. The use of stable isotope-labeled peptides allows absolute quantification of the M-protein and increases the potential of assay standardization across multiple laboratories. Finally, we discuss the position of mass-spectrometry assays in monitoring minimal residual disease in multiple myeloma, which is currently dominated by molecular techniques based on plasma cell assessment that requires invasive bone marrow aspirations or biopsies.
Targeting Attenuated Interferon-α to Myeloma Cells with a CD38 Antibody Induces Potent Tumor Regression with Reduced Off-Target Activity. [2021]Interferon-α (IFNα) has been prescribed to effectively treat multiple myeloma (MM) and other malignancies for decades. Its use has waned in recent years, however, due to significant toxicity and a narrow therapeutic index (TI). We sought to improve IFNα's TI by, first, attaching it to an anti-CD38 antibody, thereby directly targeting it to MM cells, and, second, by introducing an attenuating mutation into the IFNα portion of the fusion protein rendering it relatively inactive on normal, CD38 negative cells. This anti-CD38-IFNα(attenuated) immunocytokine, or CD38-Attenukine™, exhibits 10,000-fold increased specificity for CD38 positive cells in vitro compared to native IFNα and, significantly, is ~6,000-fold less toxic to normal bone marrow cells in vitro than native IFNα. Moreover, the attenuating mutation significantly decreases IFNα biomarker activity in cynomolgus macaques indicating that this approach may yield a better safety profile in humans than native IFNα or a non-attenuated IFNα immunocytokine. In human xenograft MM tumor models, anti-CD38-IFNα(attenuated) exerts potent anti-tumor activity in mice, inducing complete tumor regression in most cases. Furthermore, anti-CD38-IFNα(attenuated) is more efficacious than standard MM treatments (lenalidomide, bortezomib, dexamethasone) and exhibits strong synergy with lenalidomide and with bortezomib in xenograft models. Our findings suggest that tumor-targeted attenuated cytokines such as IFNα can promote robust tumor killing while minimizing systemic toxicity.