QXL138AM for Multiple Myeloma

Recruiting at 7 trial locations

Overseen By David Stover, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Nammi Therapeutics Inc

Must not be taking: QT prolonging drugs

Disqualifiers: Cardiac disease, Infections, Liver disease, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial focuses on testing a new treatment called QXL138AM, a masked immunocytokine composed of an anti-CD138 immunoglobulin G1 antibody fused to interferon alpha 2a, for individuals with multiple myeloma, a type of blood cancer resistant to standard treatments. The main goal is to assess the safety of this new treatment and its behavior in the body. The trial will begin by determining the appropriate dose and then expand to evaluate its effectiveness. Candidates may qualify if they have multiple myeloma that has not responded to at least three other treatments. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

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.

Is there any evidence suggesting that QXL138AM is likely to be safe for humans?

Research shows that QXL138AM remains in the early stages of human testing, so detailed safety information is not yet available. In studies like this, researchers begin with low doses to observe the body's response. The goal is to identify the safest dose that remains effective against the disease.

Currently, researchers are testing QXL138AM to assess its safety and tolerability. As this is the first human trial, side effects may occur, but any serious side effects will be closely monitored. It is important to note that, as an early-phase study, information about safety is still being gathered. This study will help researchers understand the safety of QXL138AM for treating multiple myeloma and other tumors. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple myeloma?

QXL138AM is unique because it offers a novel approach to treating multiple myeloma, a type of blood cancer. Unlike standard treatments such as proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, QXL138AM is being explored for its potential to precisely target cancer cells with a new mechanism of action. Researchers are excited about this treatment because it may provide a more targeted attack on myeloma cells, potentially leading to better outcomes with fewer side effects. Additionally, the study includes dose escalation and expansion phases, which aim to determine the optimal and most effective dosage, potentially enhancing the treatment's efficacy and safety profile.

What evidence suggests that QXL138AM could be an effective treatment for multiple myeloma?

Research has shown that QXL138AM has promising results in early studies for treating multiple myeloma, a type of blood cancer. This trial includes a Phase 1a dose escalation arm and a Phase 1b dose expansion arm specifically for multiple myeloma. QXL138AM targets a protein called CD138, found on myeloma cells, and uses a special method to deliver a strong immune protein directly to these cancer cells. In lab tests, QXL138AM caused tumors to shrink or disappear in models of multiple myeloma. These results suggest it could be an effective treatment, although it remains in the early stages of research. ^{1 2 3 6 7}

Who Is on the Research Team?

Dennis Kim, MD

Principal Investigator

Nammi Therapeutics Inc

Are You a Good Fit for This Trial?

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.

My organs and bone marrow are functioning well.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• QXL138AM

Trial Overview The 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.

How Is the Trial Designed?

Group I: Phase 1b Dose Expansion in Solid Tumors - Part B1 Experimental Treatment 1 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 B2 Experimental Treatment 1 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 A1 Experimental Treatment 1 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 A2 Experimental Treatment 1 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

Who Is Running the Clinical Trial?

Nammi Therapeutics Inc

Lead Sponsor

Trials

1

Recruited

100+

Published Research Related to This Trial

KappaMab (KM) is a monoclonal antibody that targets the kappa myeloma antigen on malignant plasma cells, showing a favorable safety profile and anti-myeloma activity in previous studies.

In a phase IIb study, KM combined with lenalidomide and dexamethasone (KM-Rd) achieved an impressive overall response rate of 82.5% in relapsed, refractory kappa-restricted multiple myeloma patients, significantly higher than the 45.1% response rate in a matched cohort receiving standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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). Spencer, A., Kalff, A., Shortt, J., et al.[2023]

The bispecific antibody 2A9-MICA effectively targets malignant plasma cells in multiple myeloma by combining the MICA protein, which activates immune cells, with a fragment that specifically binds to BCMA, enhancing immune response against the cancer.

In preclinical studies with BCMA-positive mice, 2A9-MICA demonstrated significant tumor growth inhibition and improved recruitment of immune cells to the tumor site, suggesting its potential as a promising immunotherapy for multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BCMA-targeting Bispecific Antibody That Simultaneously Stimulates NKG2D-enhanced Efficacy Against Multiple Myeloma. Wang, Y., Li, H., Xu, W., et al.[2021]

The novel antibody-drug conjugate J6M0-mcMMAF (GSK2857916) effectively targets B-cell maturation antigen (BCMA) on multiple myeloma (MM) cells, leading to significant cell growth inhibition and apoptosis through multiple mechanisms, including G2/M cell cycle arrest and caspase 3 activation.

In preclinical models, J6M0-mcMMAF demonstrated strong anti-tumor activity, rapidly eliminating myeloma cells and maintaining tumor-free status in mice for up to 3.5 months, highlighting its potential as a promising immunotherapeutic option for treating multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel anti-B-cell maturation antigen antibody-drug conjugate (GSK2857916) selectively induces killing of multiple myeloma. Tai, YT., Mayes, PA., Acharya, C., et al.[2023]

Researchers developed monoclonal antibodies (MAbs) targeting unique surface markers of the U266 multiple myeloma cell line, with the best fusion efficiency achieved at an immunogen concentration of 10 microg.

Out of 147 screened supernatants, seven MAbs were identified as specific to myeloma cells, suggesting potential for use in imaging, phenotyping, and targeted therapy for multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Generation of monoclonal antibodies to surface proteins of human multiple myeloma employing membrane extracts for murine in vivo immunizations. Ravi, M., Balaji, S., Srinivasan, L., et al.[2009]

A new serum-based targeted mass-spectrometry assay has been developed that can accurately detect M-proteins in multiple myeloma patients, even when they are receiving therapeutic monoclonal antibodies, which conventional methods struggle to differentiate.

This mass-spectrometry assay is over 100 times more sensitive than traditional M-protein diagnostics, allowing for better monitoring of disease response and potentially reducing the risk of overtreatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of a Targeted Mass-Spectrometry Serum Assay To Quantify M-Protein in the Presence of Therapeutic Monoclonal Antibodies. Zajec, M., Jacobs, JFM., Groenen, PJTA., et al.[2018]

The new anti-CD38-IFNα(attenuated) immunocytokine shows a remarkable 10,000-fold increase in targeting specificity for multiple myeloma cells compared to standard IFNα, while being 6,000-fold less toxic to normal bone marrow cells, suggesting a much safer treatment option.

In human xenograft models, this targeted therapy not only induces complete tumor regression in many cases but also outperforms standard multiple myeloma treatments, indicating its potential as a more effective and safer alternative for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting Attenuated Interferon-α to Myeloma Cells with a CD38 Antibody Induces Potent Tumor Regression with Reduced Off-Target Activity. Pogue, SL., Taura, T., Bi, M., et al.[2021]

Multiple myeloma is a promising target for immune therapies due to its unique plasma cell biology and bone marrow environment, allowing for treatments that can selectively kill cancer cells with minimal side effects.

Recent advancements in immune therapies, including immune modulatory drugs, targeted antibodies, CAR-T cell therapies, and vaccines, have led to improved treatment options with enhanced effectiveness and specificity against multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Keeping Myeloma in Check: The Past, Present and Future of Immunotherapy in Multiple Myeloma. Ackley, J., Ochoa, MA., Ghoshal, D., et al.[2023]

Immunotherapy has emerged as a promising treatment for multiple myeloma, a type of cancer that affects plasma cells, especially for patients with relapsed or refractory disease.

Various immunotherapeutic strategies, including immunomodulatory drugs, checkpoint inhibitors, monoclonal antibodies, engineered T cells, and vaccines, have shown encouraging results and may improve patient outcomes by reversing the immune suppression caused by the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Strategies in Multiple Myeloma: Immunotherapy as a Novel Approach to Treat Patients with Multiple Myeloma. Neri, P., Bahlis, NJ., Lonial, S.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06582017

NCT06582017 | Safety, PK and Efficacy of QXL138AM in ... Study QXL138AM-001 is a Phase 1a/1b study to investigate the safety, pharmacokinetics, and preliminary activity of QXL138AM in subjects with locally ...

2. targetedonc.com targetedonc.com/view/study-launches-of-qxl138am-in-multiple-myeloma-and-solid-tumors

Study Launches of QXL138AM in Multiple Myeloma and ... Patient dosing has begun in a phase 1 trial evaluating QXL138AM, a masked immunocytokine targeting CD138, in advanced solid tumors and multiple myeloma.

3. nycancer.com nycancer.com/trials/Nammi_QXL138AM-001

Safety, PK and Efficacy of QXL138AM in Patients With ... Full Title Protocol QXL138AM-001: A First-in-human Phase 1a/1b Study to Evaluate Safety and Tolerability of QXL138AM in Patients With Loc.

4. ctsearchsupport.org ctsearchsupport.org/clinical-trials/safety-pk-and-efficacy-of-qxl138am-in-patients-with-solid-tumors-and-multiple-myeloma

A drug, QXL138AM, to treat multiple myeloma that has ... To find out:The highest dose of QXL138AM that's safe to giveIf QXL138AM is safe and works well to treat multiple myeloma that has relapsed ...

5. synapse.patsnap.com synapse.patsnap.com/drug/f3ea9104ed2244d0ae86eddb76c40edc

QXL-138AM - Drug Targets, Indications, Patents Preclinical data has demonstrated significant anti-tumor efficacy across more than 10 tumor types including multiple myeloma where complete regression at doses ...

6. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/531095

Safety, PK and Efficacy of QXL138AM in Patients With ... Study QXL138AM-001 is a Phase 1a/1b study to investigate the safety, pharmacokinetics, and preliminary activity of QXL138AM in subjects with ...

7. nyhealth.com nyhealth.com/embed/astr-trial/Nammi_QXL138AM-001

Condition: Solid Tumors or Multiple Myeloma QXL138AM-001: Safety, PK and Efficacy of QXL138AM in Patients With Solid Tumors and Multiple Myeloma. Condition: Solid Tumors or Multiple Myeloma. Sponsor ...