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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests NX-2127, an experimental treatment, to determine its safety and effectiveness for advanced B-cell cancers, such as certain lymphomas and leukemias, that no longer respond to standard treatments. The trial seeks to identify the optimal dose of NX-2127 to combat these cancers. It includes different groups, each targeting specific cancer types that resisted previous therapies. Individuals whose B-cell cancer has progressed despite other treatments might be suitable candidates for this study. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that NX-2127 is likely to be safe for humans?

Research has shown that NX-2127 has a safety profile manageable for patients with B-cell cancers. In earlier studies, patients with conditions like chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) handled the treatment. Some side effects were reported, but these are common in cancer treatments and were considered manageable. Evidence suggests that NX-2127 is generally well-tolerated, though it remains in an early testing stage. Participants should discuss any concerns and potential risks with their healthcare providers before deciding to join a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about NX-2127 because it offers a novel approach for treating B-cell malignancies, specifically for patients whose disease has not responded to existing therapies like BTK inhibitors and anti-CD20 monoclonal antibodies. Unlike traditional therapies, NX-2127 is designed to target and degrade specific proteins crucial to cancer cell survival, potentially leading to more effective treatment outcomes. This targeted protein degradation mechanism is a cutting-edge strategy that could overcome resistance seen in standard treatments, making it a promising option for patients with limited alternative therapies.

What evidence suggests that NX-2127 might be an effective treatment for B-cell malignancies?

Research shows that NX-2127, the investigational treatment in this trial, may help treat B-cell cancers. Studies have found that it targets a specific pathway effective for conditions like chronic lymphocytic leukemia (CLL). NX-2127 might surpass traditional treatments by overcoming resistance caused by genetic changes. Early results suggest it is safe and has anti-cancer effects in patients whose B-cell cancers have returned or are difficult to treat. While more information is needed, the initial findings are promising for those with these challenging cancers. Participants in this trial will receive NX-2127 in various treatment arms, each tailored to specific B-cell malignancies and stages of dose optimization. ^{2 6 7 8 9}

Who Is on the Research Team?

Paula O'Connor, MD

Principal Investigator

Nurix Therapeutics, Inc.

Are You a Good Fit for This Trial?

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

I have an active autoimmune condition affecting my blood.

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. ashpublications.org ashpublications.org/blood/article/140/Supplement%201/2329/491381/NX-2127-001-a-First-in-Human-Trial-of-NX-2127-a

NX-2127-001, a First-in-Human Trial of NX-2127, a Bruton's ... Targeting this pathway has proven highly effective in patients with chronic lymphocytic leukemia (CLL) and other B-cell malignancies. However, ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04830137

A Study of NX-2127 in Adults With Relapsed/Refractory B- ... 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 ...

3. cllsociety.org cllsociety.org/2023/03/ash-2022-nx-2127-001-a-first-in-human-trial-of-nx-2127/

ASH 2022: NX-2127-001, a First-in-Human Trial of ... This study is designed to evaluate the safety, tolerability, and preliminary efficacy of patients with relapsed or refractory CLL / SLL and ...

4. nurixtx.com nurixtx.com/wp-content/uploads/2024/12/NX-2127-ASH-2023-poster-14-Nov-2023-FINAL.pdf

A First-in-Human Phase 1 Trial of NX-2127, a ... NX-2127 may exert superior anti-tumor activity compared with classical BTKi by overcoming BTK mutation-driven resistance to BTKi, eliminating ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497123110640

A First-in-Human Phase 1 Trial of NX-2127, ... Preliminary safety of NX-2127 in patients across B cell malignancies and efficacy in patients with CLL have been presented previously [Mato et al. 2022 ...

6. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/4463/501752/A-First-in-Human-Phase-1-Trial-of-NX-2127-a-First

A First-in-Human Phase 1 Trial of NX-2127, a First-in-Class ... Preliminary safety of NX-2127 in patients across B cell malignancies and efficacy in patients with CLL have been presented previously [Mato et ...

7. nurixtx.com nurixtx.com/wp-content/uploads/2024/02/NX-2127-ICHM-2024-poster-27-Feb-2024-FINAL.pdf

A First-in-Human Phase 1 Trial of NX-2127, a ... B-cell malignancies (NX-2127-001). Preliminary safety data across B-cell malignancies and efficacy in patients with CLL have been presented previously.3,4. • ...

8. cllsociety.org cllsociety.org/2024/02/safety-of-btk-degrader-nx-2127-for-b-cell-malignancies/

Safety of BTK Degrader NX-2127 for B Cell Malignancies NX-2127 is a new type of drug that degrades BTK. Phase 1 clinical trial data shows that it has a manageable safety profile in patients with CLL / SLL.

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.TPS7581

A first-in-human phase 1 trial of NX-2127, a first-in-class ... NX-2127 is an oral small molecule that induces BTK degradation via recruitment of cereblon, an adaptor protein of the E3 ubiquitin ligase complex.