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

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. ^{1 2 3 4 5}

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. ^{1 2 6 7 8}

Research Team

Dennis Kim, MD

Principal Investigator

Nammi Therapeutics Inc

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.

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

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

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

BCMA-targeting Bispecific Antibody That Simultaneously Stimulates NKG2D-enhanced Efficacy Against Multiple Myeloma. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Generation of monoclonal antibodies to surface proteins of human multiple myeloma employing membrane extracts for murine in vivo immunizations. [2009]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Keeping Myeloma in Check: The Past, Present and Future of Immunotherapy in Multiple Myeloma. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

New Strategies in Multiple Myeloma: Immunotherapy as a Novel Approach to Treat Patients with Multiple Myeloma. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Novel anti-B-cell maturation antigen antibody-drug conjugate (GSK2857916) selectively induces killing of multiple myeloma. [2023]

6. England 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). [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Development of a Targeted Mass-Spectrometry Serum Assay To Quantify M-Protein in the Presence of Therapeutic Monoclonal Antibodies. [2018]

8. United States 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. [2021]