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-1607 in patients 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 as monotherapy or in combination with paclitaxel at the dose(s) selected in Phase 1a in 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, MSS CRC, mixed solid tumor cohort indications consisting of patients with MPM, TNBC, locally advanced or metastatic urothelial cancer, cervical cancer, and DLBCL including patients with DLBCL-RT. In Arm 1 (NX-1607 monotherapy), more than 1 dose level of NX-1607 may be tested in individual indications, each of which will constitute a separate cohort in Phase 1b.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
345
Oral NX-1607
Paclitaxel IV
City of Hope
Duarte, California, United States
COMPLETEDUniversity of Southern California
Los Angeles, California, United States
RECRUITINGUniversity of California, San Francisco
San Francisco, California, United States
RECRUITINGUniversity of Colorado School of Medicine
Aurora, Colorado, United States
RECRUITINGUniversity of Chicago
Chicago, Illinois, United States
RECRUITINGUniversity of North Carolina
Chapel Hill, North Carolina, United States
RECRUITINGUniversity of Oklahoma
Oklahoma City, Oklahoma, United States
RECRUITINGMD Anderson Cancer Center
Houston, Texas, United States
RECRUITINGUniversity of Virginia
Charlottesville, Virginia, United States
RECRUITINGFred Hutchinson Cancer Center
Seattle, Washington, United States
RECRUITING...and 7 more locations
Incidence of treatment-emergent adverse events (TEAEs), including Grade ≥ 3 TEAEs, treatment-emergent serious adverse events (SAEs), TEAEs leading to study drug discontinuation, and deaths due to TEAEs
Phase 1a
Time frame: 16 months
Incidence of immune-related AEs (irAEs), all deaths, and dose-limiting toxicities (DLTs)
Phase 1a
Time frame: Up to 2 Years
Objective Response Rate (ORR) per disease-specific response criteria as assessed by the Investigator
Phase 1b
Time frame: Up to 3 Years
PK parameters of NX-1607: area under the curve (AUC)
Phase 1a/1b - Sampling following the first dose, pre and post-dose at selected cycles, and at the end of treatment
Time frame: Up to 3 Years
PK parameters of NX-1607: apparent clearance (CL/F)
Phase 1a/1b - Sampling following the first dose, pre and post-dose at selected cycles, and at the end of treatment
Time frame: Up to 3 Years
PK parameters of NX-1607: maximum plasma concentration (Cmax)
Phase 1a/1b - Sampling following the first dose, pre and post-dose at selected cycles, and at the end of treatment
Time frame: Up to 3 Years
PK parameters of NX-1607: volume of distribution
Phase 1a/1b - Sampling following the first dose, pre and post-dose at selected cycles, and at the end of treatment
Time frame: Up to 3 Years
PK parameters of NX-1607: half-life and time to maximum plasma concentration
Phase 1a/1b - Sampling following the first dose, pre and post-dose at selected cycles, and at the end of treatment
Time frame: Up to 3 Years
PK parameters of NX-1607: accumulation ratio (Racc)
Phase 1a/1b - Sampling following the first dose, pre and post-dose at selected cycles, and at the end of treatment
Time frame: Up to 3 Years
PD Biomarkers: Changes from baseline in inflammatory cytokine expression in the circulating immune cells
Phase 1a/1b - Sampling following the first dose, pre and post-dose at selected cycles, and at the end of treatment
Time frame: Up to 3 Years
Objective response rate (ORR) per disease-specific response criteria as assessed by the Investigator
Phase 1a
Time frame: Up to 3 Years
Duration of response (DOR) as assessed by the Investigator
Phase 1a/1b
Time frame: Up to 3 Years
Disease control rate (DCR) as assessed by the Investigator
Phase 1a/1b
Time frame: Up to 3 Years
Progression-free survival (PFS) as assessed by the Investigator
Phase 1a/1b
Time frame: Up to 3 Years
Overall survival (OS) as assessed by the Investigator
Phase 1a/1b
Time frame: Up to 3 Years
Incidence of TEAEs, including Grade ≥ 3 TEAEs, treatment emergent SAEs, TEAEs leading to study drug discontinuation, and deaths due to TEAEs
Phase 1b
Time frame: Up to 3 Years
Time to disease progression assessed by the Investigator (according to relevant disease histology)
Phase 1b
Time frame: Up to 3 Years
Incidence of IrAEs and all deaths
Phase 1b
Time frame: Up to 3 Years
Time from start of treatment to disease progression based on PCWG3 criteria
Phase 1b (mCRPC cohort only)
Time frame: Up to 3 Years
PD Biomarkers: Changes from baseline in tumor tissue biopsies of immune cell infiltration or other histological features
Phase 1b
Time frame: Up to 3 Years
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