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 1 prior therapy for patients with WM) and for whom no
other therapies are known to provide clinical benefit. Phase 1b will investigate the efficacy
of NX-2127 at the dose 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 1 prior
therapy for patients with WM):
- Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) with no BTK C481
mutation
- BTK C481 mutation-positive CLL/SLL
- Mantle Cell Lymphoma (MCL), Marginal Zone Lymphoma (MZL) or Waldenstrom
Macroglobulinemia (WM)
- Follicular lymphoma (FL)
- Diffuse Large B-cell Lymphoma (DLBCL)
Inclusion Criteria:
- Patients must be ≥ 18 years of age
- Patients must have measurable disease per disease-specific response criteria
- Patients with indolent forms of NHL must meet the criteria requiring systemic
treatment (i.e., iwCLL, IWG, or Lugano Classification of Lymphoma response criteria)
- Patients with transformed lymphoma are eligible for the study with the exception of
those who have Richter's transformation, prolymphocytic leukemia, or blastoid lymphoma
prior to planned start of study drug
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Adequate organ and bone marrow function, in the absence of growth factors
- Patients of child-bearing potential must use adequate contraceptive measures to avoid
pregnancy for the duration of the study as defined in the protocol
Inclusion Criteria for Patients in Phase 1a:
- Have histologically confirmed R/R CLL, SLL, WM, MCL, and MZL, FL(grade 1 - 3b), and
DLBCL (High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements and
high-grade B-cell lymphoma NOS)
- Received at least 2 prior systemic therapies (or 1 prior therapy for patients with WM)
and have no other therapies known to provide clinical benefit
- Must require systemic therapy
Inclusion Criteria for Patients in Phase 1b:
- Must have one of the following histologically documented R/R B-cell malignancies:
- CLL/SLL with no BTK C481 mutation whose disease has failed treatment with a BTKi;
- BTK C481 mutation-positive CLL/SLL whose disease has failed treatment with a
BTKi;
- MCL or MZL whose disease has failed treatment with BTKi and an anti-CD20
mAb-based regimen or WM whose disease has failed treatment with BTKi
- FL (grade 1 - 3b) whose disease has failed treatment with anti-CD20 mAb-based
regimen;
- DLBCL whose disease has failed treatment with an anti-CD20 mAb-based regimen and
an anthracycline (either progressed post stem cell transplant or
transplant-ineligible)
- DLBCL histologies include high-grade B-cell lymphoma, with MYC and BCL2
and/or BCL6 rearrangements and high-grade B-cell lymphoma NOS
Exclusion Criteria:
- History of CNS lymphoma/leukemia in remission for less than 2 years
- Active, uncontrolled autoimmune hemolytic anemia or autoimmune thrombocytopenia
- History of known/suspected other autoimmune disease (exception(s): patients with
vitiligo, resolved childhood atopic dermatitis, hypothyroidism, or hyperthyroidism
that is clinically euthyroid at screening are allowed.)
- Unable to swallow capsules or have a condition that may interfere in the delivery,
absorption, or metabolism of the study drug
- Bleeding diathesis, or other known risk for acute blood loss
- Patients requiring ongoing treatment with chronic, therapeutic anticoagulation with
warfarin or patients treated with dual anti-platelet therapy and vitamin K antagonists
- Prior radiotherapy within 2 weeks of planned start of study drug (excluding limited
palliative radiation)
- Toxicities from previous anticancer therapies must have resolved to baseline levels or
to Grade 1 (except for alopecia, hypothyroidism with adequate replacement therapy,
hypopituitarism with adequate replacement therapy, peripheral neuropathy or
hematologic parameters meeting inclusion criteria).
- Active known second malignancy with the exception of any of the following:
- Adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or
in situ cervical cancer;
- Adequately treated Stage I cancer from which the patient is currently in
remission and has been in remission for ≥ 2 years;
- Low-risk prostate cancer with Gleason score < 7 and prostate-specific antigen <
10 ng/mL; or
- Any other cancer from which the patient has been disease-free for ≥ 2 years
- Patient has had major surgery (e.g. requiring general anesthesia) within 4 weeks
before the planned first dose of study drug
- Infection with human immunodeficiency virus (HIV)-1 or HIV-2. Exception: patients with
well-controlled HIV (e.g., CD4 > 350/mm3 and undetectable viral load) are eligible.
- Current active liver disease from any cause
- Active viral reactivation (e.g., CMV or EBV)
- Use of systemic corticosteroids (> 20 mg/day prednisone or equivalent)
- Clinically significant, uncontrolled cardiac, cardiovascular disease, or history of
myocardial infarction within 6 months of planned start of study drug
- Patient is taking strong or moderate cytochrome P450 3A (CYP3A) inducers or inhibitors
or inhibitors of P-glycoprotein
