A Study of NX-2127 in Adults With Relapsed/Refractory 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-5948 in Adults With Relapsed/Refractory 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 and for whom no other therapies are known to provide clinical benefit. Indications include: Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL), non-germinal center B-cell subtype (non-GCB) Diffuse Large B-cell Lymphoma (DLBCL), Mantle Cell Lymphoma (MCL), Waldenstrom Macroglobulinemia (WM), Marginal Zone Lymphoma (MZL), Follicular Lymphoma (FL) including those with secondary CNS involvement in any disease indication listed, 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 4 cohorts of patients with histologically confirmed R/R B-cell malignancy indications who have received at least 2 prior lines of therapy (or at least 1 prior line for patients with WM or PCNSL):

CLL or SLL including those with secondary CNS involvement of their disease
Non-GCB DLBCL or MCL including those with secondary CNS involvement of their disease
MZL, WM, or FL including those with secondary CNS involvement of their disease
PCNSL

A Study of NX-1607 in Adults With Advanced Malignancies

Phase 1a will consist of 2 study arms: Monotherapy and Paclitaxel combo. Phase 1a dose escalation will evaluate the safety and tolerability of NX-1607 in adult patients with advanced solid tumors for which standard therapy with proven clinical benefit does not exist, is no longer effective, or is not appropriate. Indications for monotherapy include platinum resistant epithelial ovarian cancer (EOC), gastric/gastroesophageal junction (GEJ) cancer, squamous cell carcinoma of the head and neck (HNSCC), recurrent and either metastatic or unresectable melanoma, non-small cell lung cancer (NSCLC), metastatic castration-resistant prostate cancer (mCRPC), malignant pleural mesothelioma (MPM), triple-negative breast cancer (TNBC), locally advanced or metastatic urothelial cancer, cervical cancer, and microsatellite stable colorectal cancer (MSS CRC), and diffuse large cell B-cell lymphoma (DLBCL) including patients with Richter transformation (DLBCL-RT). Indications for paclitaxel combo may include, but are not limited to, platinum-resistant EOC, gastric/GEJ cancer, HNSCC, NSCLC, TNBC, locally advanced or metastatic urothelial cancer, and cervical cancer at the Sponsor’s discretion.

Phase 1b will investigate the efficacy of NX-1607 monotherapy at the dose selected in Phase 1a in up to 8 cohorts of patients with select advanced malignancies for which standard therapy, including immunotherapy, with proven clinical benefit does not exist, is no longer effective, or is not appropriate. Indications include platinum-resistant EOC, including primary peritoneal and fallopian tube carcinoma, advanced gastric/GEJ cancer, HNSCC, recurrent and either metastatic or unresectable melanoma, advanced NSCLC, mCRPC, mixed solid tumor cohort indications consisting of patients with MPM, TNBC, locally advanced or metastatic urothelial cancer, cervical cancer, or MSS CRC, and DLBCL including patients with DLBCL-RT.