NX-2127 for B-cell Malignancies

Recruiting at 7 trial locations

Overseen By Patient Outreach

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Nurix Therapeutics, Inc.

Must not be taking: Warfarin, Corticosteroids, Immunosuppressives, others

Disqualifiers: Autoimmune disease, Active liver disease, others

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

Compensation: Varies

Number of Visits: Unknown

248 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a first-in-human Phase 1a/1b multicenter, open-label oncology study designed to evaluate the safety and anti-cancer activity of NX-2127 in patients with advanced B-cell malignancies.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting, such as strong CYP3A inducers or inhibitors, P-glycoprotein inhibitors, and non-steroidal immunosuppressive drugs. If you are on warfarin or similar medications, you must stop them 7 days before the trial. Please consult with the trial team for specific guidance on your medications.

What data supports the effectiveness of the drug NX-2127 for B-cell malignancies?

Research on similar treatments shows that targeting specific pathways in B-cell malignancies, like the B-cell receptor signaling pathway, has been promising. Drugs targeting these pathways have shown activity in various types of lymphoma and leukemia, suggesting potential effectiveness for NX-2127. ^{1 2 3 4 5}

How is the drug NX-2127 different from other treatments for B-cell malignancies?

NX-2127 is unique because it represents a shift from traditional chemotherapy to more selective agents that target specific cellular pathways involved in B-cell malignancies. This approach focuses on disrupting key pathways that drive cancer cell growth and survival, potentially offering more effective and targeted treatment options. ^{1 2 4 6 7}

Research Team

Paula O'Connor, MD

Principal Investigator

Nurix Therapeutics, Inc.

Eligibility Criteria

Adults with certain types of blood cancer who've had at least two prior treatments (or one for specific conditions) can join this trial. They must be over 18, not pregnant, and have a good performance status. People with uncontrolled diseases, recent major surgery or radiation, active infections like HIV or hepatitis, or autoimmune diseases aren't eligible.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

My cancer is a confirmed type of blood or lymphatic system cancer.

Patients of child-bearing potential must use adequate contraceptive measures to avoid pregnancy for the duration of the study as defined in the protocol

Exclusion Criteria

I have an active autoimmune condition affecting my blood.

I haven't taken strong medication affecting liver enzymes or certain drug transporters in the last 2 weeks.

I haven't had radiotherapy in the last 2 weeks, except for palliative care.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1a Dose Escalation

Evaluate the safety and tolerability of NX-2127 in adult patients with relapsed/refractory B-cell malignancies

Up to 24 months

Phase 1b Dose Optimization

Further investigate the safety, tolerability, and preliminary efficacy of NX-2127 in R/R B-cell malignancies

Up to 4 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Treatment Details

Interventions

• NX-2127

Trial Overview The study is testing NX-2127's safety and effectiveness against advanced B-cell malignancies. It's an early-stage trial where all participants receive the same experimental drug to see how well it works and what side effects it may cause.

Participant Groups

Group I: Phase 1b Dose Optimization Stage 2 in PCNSL (Randomized to Dose A or Dose B) Experimental Treatment 1 Intervention

PCNSL patients whose disease has failed at least 1 prior line of treatment

Group II: Phase 1b Dose Optimization Stage 2 in MCL (Randomized to Dose A or Dose B) Experimental Treatment 1 Intervention

MCL patients whose disease has failed treatment with a BTK inhibitor and an anti-CD20 monoclonal antibody (mAb) based regimen

Group III: Phase 1b Dose Optimization Stage 2 in FL, MZL or WM (Randomized to Dose A or Dose B) Experimental Treatment 1 Intervention

FL or MZL patients whose disease has failed treatment with an anti-CD20 mAb-based regimen; or WM whose disease has failed treatment with a BTK inhibitor

Group IV: Phase 1b Dose Optimization Stage 2 in DLBCL (Randomized to Dose A or Dose B) Experimental Treatment 1 Intervention

DLBCL patients whose disease has failed treatment with an anti-CD20 mAb-based regimen and either: an anthracycline-based regimen; or an anti-CD19-based regimen; or another/palliative regimen

Group V: Phase 1b Dose Optimization Stage 2 in CLL or SLL (Randomized to Dose A or Dose B) Experimental Treatment 1 Intervention

CLL/SLL patients whose disease has failed treatment with a BTK inhibitor

Group VI: Phase 1b Dose Optimization Stage 1 in PCNSL (Dose A) Experimental Treatment 1 Intervention

PCNSL patients whose disease has failed at least 1 prior line of treatment

Group VII: Phase 1b Dose Optimization Stage 1 in MCL (Dose A) Experimental Treatment 1 Intervention

MCL patients whose disease has failed treatment with a BTK inhibitor and an anti-CD20 monoclonal antibody (mAb) based regimen

Group VIII: Phase 1b Dose Optimization Stage 1 in FL, MZL or WM (Dose A) Experimental Treatment 1 Intervention

FL or MZL patients whose disease has failed treatment with an anti-CD20 mAb-based regimen; or WM whose disease has failed treatment with a BTK inhibitor

Group IX: Phase 1b Dose Optimization Stage 1 in DLBCL (Dose A) Experimental Treatment 1 Intervention

DLBCL patients whose disease has failed treatment with an anti-CD20 mAb-based regimen and either: an anthracycline-based regimen; or an anti-CD19-based regimen; or another/palliative regimen

Group X: Phase 1b Dose Optimization Stage 1 in CLL or SLL (Dose A) Experimental Treatment 1 Intervention

CLL/SLL patients whose disease has failed treatment with a BTK inhibitor

Group XI: Phase 1a Dose Escalation Experimental Treatment 1 Intervention

Multiple dose levels of NX-2127 to be evaluated; determination of MTD/Phase 1b recommended dose

Who Is Running the Clinical Trial?

Nurix Therapeutics, Inc.

Lead Sponsor

Trials

7

Recruited

1,100+

Findings from Research

In a study of 167 non-Hodgkin's lymphoma patients, combining Chinese herbs with chemotherapy resulted in a significantly higher effective rate (91.96%) and improved survival rates compared to chemotherapy alone (72.73%).

The combination therapy not only enhanced immune function, as indicated by increased NK cell activity, but also reduced blood viscosity, with fewer and milder side effects compared to chemotherapy alone, suggesting it is a safe and effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical observation on 112 cases with non-Hodgkin's lymphoma treated by Chinese herbs combined with chemotherapy]. Guo, XM., Li, JX., Yang, XF.[2016]

Recent advancements in understanding the pathways driving malignant B-cell development have led to the creation of more selective therapies, moving away from traditional chemotherapy.

New targeted agents, including those that inhibit key pathways like B-cell receptor signaling and apoptosis regulators, are showing promise in treating various subtypes of lymphoma and leukemia, with many currently in early clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Developing novel strategies to target B-cell malignancies. Fowler, N., Oki, Y.[2021]

In a phase II study involving 42 patients with previously untreated indolent non-Hodgkin's lymphoma, the combination of rituximab and CNOP chemotherapy achieved a high overall response rate of 90%, with 71% of patients experiencing complete responses.

The treatment was well tolerated, with only 2% of patients experiencing severe infusion-related toxicity, indicating that rituximab plus CNOP is an effective and safe option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab in combination with CNOP chemotherapy in patients with previously untreated indolent non-Hodgkin's lymphoma. Economopoulos, T., Fountzilas, G., Pavlidis, N., et al.[2016]

Rituximab, a chimeric anti-CD20 monoclonal antibody, has shown to induce responses in nearly 50% of patients with relapsed follicular/low-grade non-Hodgkin's lymphoma, with complete remissions occurring in 6% of cases, highlighting its efficacy in treating this type of cancer.

The drug is generally well tolerated, with common side effects being mild to moderate fevers and chills, and it is also effective against various other B-cell malignancies, suggesting its potential for broader applications in both cancer treatment and autoimmune disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab: clinical development and future directions. Cheson, BD.[2019]

The CIBO-P regimen, a novel combination therapy for recurrent or refractory aggressive non-Hodgkin lymphoma, showed a high overall objective response rate of 77% in 39 evaluable patients, with 49% achieving complete responses.

Despite myelosuppression being the most common serious side effect, the treatment was considered safe, with only 5% of patients experiencing febrile neutropenia, indicating that CIBO-P is a promising option for patients with poor prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lomustine (chloroethylnitrosourea [CCNU]), ifosfamide, bleomycin, vincristine, and cisplatin (CIBO-P) is an effective regimen for patients with poor prognostic refractory or multiple disease recurrent aggressive non-Hodgkin lymphoma. Musolino, A., Perrone, MA., Michiara, M., et al.[2015]

Recent advances in understanding the mechanisms of malignant tumors have led to the development of novel targeted therapies for malignant lymphomas, particularly B-cell lymphomas (B-NHL).

Current research includes a variety of tailored approaches, such as monoclonal antibodies and the inhibition of specific molecules, which are being tested in both preclinical studies and clinical trials, indicating a promising future for personalized treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New targeted therapies for malignant lymphoma based on molecular heterogeneity. Horn, H., Staiger, AM., Ott, G.[2017]

SGN-CD19B is a promising anti-CD19 antibody drug conjugate that shows improved potency in treating relapsed/refractory B-cell malignancies, inducing cell death through a unique mechanism that causes DNA damage rather than using traditional microtubule inhibitors.

In preclinical studies, SGN-CD19B demonstrated effective and durable tumor regressions at lower doses compared to other antibody drug conjugates, and it was well-tolerated in cynomolgus monkeys, indicating its potential for safe clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic potential of SGN-CD19B, a PBD-based anti-CD19 drug conjugate, for treatment of B-cell malignancies. Ryan, MC., Palanca-Wessels, MC., Schimpf, B., et al.[2021]

References

1. China pubmed.ncbi.nlm.nih.gov

[Clinical observation on 112 cases with non-Hodgkin's lymphoma treated by Chinese herbs combined with chemotherapy]. [2016]

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

Developing novel strategies to target B-cell malignancies. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Rituximab in combination with CNOP chemotherapy in patients with previously untreated indolent non-Hodgkin's lymphoma. [2016]

4. England pubmed.ncbi.nlm.nih.gov

Rituximab: clinical development and future directions. [2019]

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

Lomustine (chloroethylnitrosourea [CCNU]), ifosfamide, bleomycin, vincristine, and cisplatin (CIBO-P) is an effective regimen for patients with poor prognostic refractory or multiple disease recurrent aggressive non-Hodgkin lymphoma. [2015]

6. England pubmed.ncbi.nlm.nih.gov

New targeted therapies for malignant lymphoma based on molecular heterogeneity. [2017]

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

Therapeutic potential of SGN-CD19B, a PBD-based anti-CD19 drug conjugate, for treatment of B-cell malignancies. [2021]