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Chronic Lymphocytic Leukemia

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Vaccines

Immunologic Factors

On day one, patients will receive the first of two doses of the Shingrix vaccine administered as an injection into the muscle in their upper arm. The second dose of vaccine will be administered as an injection to their upper arm approximately 2 months after the first dose.

Shingrix vaccine

Jonathan Friedberg, MD

The primary objective of the study is to assess the capability of a patient with Chronic Lymphocytic Leukemia (CLL) or Waldenström Macroglobulinemia (WM) to generate an immune response to the Shingrix vaccine under first-line BTK inhibitors.

Chronic lymphocytic leukemia (CLL) and Waldenstrom's macroglobulinemia (WM) are known risk factors for zoster reactivation, commonly called shingles. Although a recently FDA-approved recombinant, adjuvanted herpes zoster vaccine (Shingrix) is currently being offered to these populations, no study has specifically evaluated them.

The purpose of the study is to complete a single-arm trial evaluating if patients with CLL or WM, while on treatment with first-line BTK inhibitors, can achieve immunologic response to Shingrix. If effective, this will result in a new, well-tolerated shingles prevention strategy for these patients.

The primary objective is to assess the capability to mount a humoral immune response to Shingrix in patients with CLL or WM under first-line BTK inhibitors.

Serologic Response to SHINGRIX Vaccine in Patients With CLL and WM Treated With BTK Inhibitors

Serologic Response to a New Recombinant, Adjuvanted Herpes Zoster Vaccine in Patients With Chronic Lymphocytic Leukemia and Waldenström Macroglobulinemia Treated With First-Line BTK Inhibitors - A Pilot Study

Vaccine response, as determined by blood antibody levels to the varicella virus glycoprotein E subunit (anti-gE); Baseline is defined as pre-vaccination anti-gE titer in seropositive subjects, and the lower limit of detection in seronegative subjects

Cellular response, as determined by measuring VZgE-specific T-cell responses in blood, 2 years after the second vaccine administration.

Cellular response, as determined by measuring VZgE-specific T-cell responses in blood, 4 weeks after the second vaccine administration.

GlaxoSmithKline

University of Rochester

Director of the Wilmot Cancer Institute

Only adverse events grade 3 and greater will be collected. Adverse events were obtained through medical chart review and self-reporting by participants.

On day one, patients will receive the first of two doses of the Shingrix vaccine administered as an injection into the muscle in their upper arm. The second dose of vaccine will be administered as an injection to their upper arm approximately 2 months after the first dose. Antibody and cellular response to vaccination will be assessed at 4 weeks and 24 months after the second dose.

Shingrix Vaccine

50 to 65 years

> 65 years

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Michael Brady

On day one, patients will receive the first of two doses of the Shingrix vaccine administered as an injection into the muscle in their upper arm. The second dose of vaccine will be administered as an injection to their upper arm approximately 2 months after the first dose. Antibody and cellular response to vaccination will be assessed at 4 weeks after the second dose.

Number of Participants With Humoral Response to Vaccination 4 Weeks After the Second Vaccine Administration

Number of Participants With Cellular Response to Vaccination 4 Weeks After the Second Vaccine Administration

On day one, patients will receive the first of two doses of the Shingrix vaccine administered as an injection into the muscle in their upper arm. The second dose of vaccine will be administered as an injection to their upper arm approximately 2 months after the first dose. Antibody and cellular response to vaccination will be assessed at 24 months after the second dose.

Number of Participants With Humoral Response to Vaccination 2 Years After the Second Vaccine Administration

Number of Participants With Cellular Response to Vaccination 2 Years After the Second Vaccine Administration

On day one, patients will receive the first of two doses of the Shingrix vaccine administered as an injection into the muscle in their upper arm. The second dose of vaccine will be administered as an injection to their upper arm approximately 2 months after the first dose.

Shingrix vaccine: On day one, patients will receive the first of two doses of the Shingrix vaccine administered as an injection into the muscle in their upper arm. The second dose of vaccine will be administered as an injection to their upper arm approximately 2 months after the first dose.

Overall Study

Lymphoma

Lymphoma, Mantle-Cell

Lymphoma, Follicular

Lymphoma, B-Cell, Marginal Zone

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Lymphoma, Non-Hodgkin

Lymphosarcoma

Mantle Cell Lymphoma

Follicular Lymphoma

B-cell Lymphoma

Marginal Zone Lymphoma

Diffuse Large B-Cell Lymphoma

Primary Central Nervous System Lymphoma

Amino Acids

Antibodies

Antibodies, Monoclonal

Immunomodulating Agents

Immunoglobulins

Tyrosine Kinase Inhibitors

Tyrosine

Multiple dose levels of NX-5948 to be evaluated; determination of Maximum Tolerated Dose/Phase 1b recommended dose(s)

CLL or SLL with prior exposure to both a Bruton's tyrosine kinase inhibitor (BTKi) and BCL-2 inhibitor, unless previously deemed ineligible for those therapies. Patients enrolled in CLL/SLL arm will be randomized to one of two dose levels. This is the only randomization component in the trial.

MCL with prior exposure to a BTKi and an anti-CD20 monoclonal antibody (mAb)-based chemo-immunotherapy regimen

MZL (EMZL, MALT, NMZL, SMZL) with prior exposure to an anti-CD20 mAb-based chemo-immunotherapy regimen and an additional line of therapy

PCNSL patients who have progressed or had no response to at least 2 prior lines of therapy, or SCNSL patients meeting criteria for non-CLL/SLL arms above with secondary CNS involvement of lymphoma

WM with prior exposure to a BTKi and an additional line of therapy

DLBCL with prior exposure to an anthracycline (unless previously deemed ineligible to receive), an anti-CD20 mAb-based chemoimmunotherapy regimen, and an additional line of therapy

FL (grade 1-3a) with prior exposure to an anti-CD20 mAb-based chemoimmunotherapy regimen and an additional line of therapy

NX-5948

Patient Outreach

Ana Ayala

Paula O'Connor, MD

This is a first-in-human Phase 1a/1b multicenter, open-label study designed to evaluate the safety and anti-cancer activity of NX-5948 in patients with advanced B-cell malignancies.

Phase 1a is a dose escalation to evaluate the safety and tolerability of NX-5948 in adult patients with relapsed/refractory (R/R) B cell malignancies who have received at least 2 prior lines of therapy, or at least 1 prior line of therapy for Primary Central Nervous System Lymphoma (PCNSL), and for whom no other therapies are known to provide clinical benefit. Indications include: Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL), Diffuse Large B-cell Lymphoma (DLBCL), Mantle Cell Lymphoma (MCL), Waldenstrom Macroglobulinemia (WM), Marginal Zone Lymphoma (MZL), Follicular Lymphoma (FL), or Primary Central Nervous System Lymphoma (PCNSL).

Phase 1b will investigate the efficacy of NX-5948 at the dose(s) selected in Phase 1a in up to 7 expansion arms of patients with histologically confirmed R/R B-cell malignancy indications who have received the specified prior therapies based on indication:

* CLL or SLL (two dose levels will be investigated for CLL/SLL)
* MCL
* MZL
* WM
* DLBCL
* FL
* PCNSL/SCNSL

A Study of NX-5948 in Adults With Relapsed/Refractory B-cell Malignancies

A Phase 1, Dose Escalation, and Cohort Expansion Study Evaluating NX-5948, a Bruton's Tyrosine Kinase (BTK) Degrader, in Adults With Relapsed/Refractory B-cell Malignancies

Phase 1a/1b - Sampling following the first dose, pre- and post-dose at selected cycles and at the end of treatment

Phase 1a/1b - Sampling at screening, following the first dose, pre and post-dose at selected cycles and at the end of treatment

Nurix Therapeutics, Inc.

Antineoplastic Agents

Lenalidomide

Pomalidomide

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

CLL/SLL patients with no BTK C481 mutation whose disease has failed treatment with a BTK inhibitor

BTK C481 mutation-positive CLL/SLL patients whose disease has failed treatment with a BTK inhibitor

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

FL or MZL patients whose disease has failed treatment with an anti-CD20 mAb-based regimen; or PCNSL whose disease has failed at least 1 prior line of treatment

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

NX-2127

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.

Phase 1a is a dose escalation to evaluate the safety and tolerability of NX-2127 in adult patients with relapsed/refractory (R/R) B-cell malignancies, who have required and received at least 2 prior systemic therapies (or at least 1 prior therapy for patients with WM or PCNSL) and for whom no other therapies are known to provide clinical benefit. Phase 1b will investigate the efficacy of NX-2127 at the dosage(s) selected in Phase 1a in up to 5 cohorts of patients with R/R B-cell malignancy indications who have received at least 2 prior systemic therapies (or at least 1 prior therapy for patients with WM or PCNSL):

* Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) with no BTK C481 mutation
* BTK C481 mutation-positive CLL/SLL
* Mantle Cell Lymphoma (MCL)
* Follicular lymphoma (FL) or Marginal Zone Lymphoma (MZL); or Primary Central Nervous System Lymphoma (PCNSL)
* Diffuse Large B-cell Lymphoma (DLBCL) or Waldenstrom Macroglobulinemia (WM)

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

A Phase 1, Dose Escalation, Safety and Tolerability Study of NX-2127, a Bruton's Tyrosine Kinase (BTK) Degrader, in Adults With Relapsed/Refractory B-cell Malignancies

Phase 1a/1b - Sampling following the first dose, pre and post-dose at selected cycles, and at the end of treatment

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Serologic Response to SHINGRIX Vaccine in Patients With CLL and WM Treated With BTK Inhibitors	NCT03771157	Chronic Lymphoc... Waldenstrom Mac...	Shingrix vaccin...	50 Years -	University of Rochester
A Study of NX-5948 in Adults With Relapsed/Refractory B-cell Malignancies	NCT05131022	Chronic Lymphoc... Small Lymphocyt... Diffuse Large B... Follicular Lymp... Mantle Cell Lym... Marginal Zone L... Waldenstrom Mac... Primary Central...	NX-5948	18 Years -	Nurix Therapeutics, Inc.
A Study of NX-2127 in Adults With Relapsed/Refractory B-cell Malignancies	NCT04830137	Chronic Lymphoc... Small Lymphocyt... Waldenstrom Mac... Mantle Cell Lym... Marginal Zone L... Follicular Lymp... Diffuse Large B... Primary Central...	NX-2127	18 Years -	Nurix Therapeutics, Inc.

Spots Global Cancer Trial Database for waldenstrom macroglobulinemia (wm)