A Study of NX-1607 in Adults With Advanced Malignancies
A Phase 1a, Dose Escalation, Safety and Tolerability Study of NX-1607, a Casitas B-lineage Lymphoma Proto-oncogene (CBL-B) Inhibitor, in Adults With Advanced Malignancies, With Phase 1b Expansion in Select Tumor Types
1 other identifier
interventional
345
2 countries
17
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Sep 2021
Longer than P75 for phase_1
17 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 22, 2021
CompletedStudy Start
First participant enrolled
September 29, 2021
CompletedFirst Posted
Study publicly available on registry
November 4, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 31, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
February 28, 2028
September 9, 2025
September 1, 2025
4.9 years
September 22, 2021
September 5, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
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
16 months
Incidence of immune-related AEs (irAEs), all deaths, and dose-limiting toxicities (DLTs)
Phase 1a
Up to 2 Years
Objective Response Rate (ORR) per disease-specific response criteria as assessed by the Investigator
Phase 1b
Up to 3 Years
Secondary Outcomes (17)
PK parameters of NX-1607: area under the curve (AUC)
Up to 3 Years
PK parameters of NX-1607: apparent clearance (CL/F)
Up to 3 Years
PK parameters of NX-1607: maximum plasma concentration (Cmax)
Up to 3 Years
PK parameters of NX-1607: volume of distribution
Up to 3 Years
PK parameters of NX-1607: half-life and time to maximum plasma concentration
Up to 3 Years
- +12 more secondary outcomes
Study Arms (12)
Phase 1a Dose Escalation of NX-1607 (monotherapy)
EXPERIMENTALMultiple dose levels and dosing regimen of NX-1607 to be evaluated; determination of MTD/Phase 1b recommended dose.
Phase 1a Food Effect
EXPERIMENTALImpact of food on NX-1607 bioavailability and tolerability to be evaluated
Phase 1b Dose Expansion in platinum-resistant EOC
EXPERIMENTALPatients with platinum-resistant EOC, including primary peritoneal and fallopian tube carcinoma
Phase 1b Dose Expansion in advanced gastric/GEJ cancer
EXPERIMENTALPatients with recurrent, locally advanced, or metastatic gastric or GEJ adenocarcinoma
Phase 1b Dose Expansion in HNSCC
EXPERIMENTALPatients with recurrent, locally advanced, or metastatic HNSCC
Phase 1b Dose Expansion in recurrent melanoma
EXPERIMENTALPatients with recurrent and either metastatic or unresectable Melanoma
Phase 1b Dose Expansion in advanced NSCLC
EXPERIMENTALPatients with Stage IV NSCLC
Phase 1b Dose Expansion in mCRPC
EXPERIMENTALPatients with mCRPC who received a minimum of 2 prior lines of therapy in the advanced setting including androgen receptor-directed therapy and a taxane-based chemotherapy and has PSA or radiographic progression
Phase 1b Dose Expansion in mixed solid tumor cohort
EXPERIMENTALCohort of mixed solid tumor indications consisting of patients with MPM, TNBC, locally advanced or metastatic urothelial cancer, cervical cancer, or DLBCL/DLBCL-RT
Phase 1a Dose Escalation of NX-1607 in combination with Paclitaxel
EXPERIMENTALIndications may include but are not limited to, platinum resistant EOC, gastric/GEJ cancer. HSNCC, NSCLC, TNBC, locally advanced or metastatic urothelial cancer and cervical cancer.
Phase 1b Dose Expansion of NX-1607 in combination with Paclitaxel
EXPERIMENTALIndications may include but are not limited to, platinum resistant EOC, gastric/GEJ cancer, HSNCC, NSCLC, TNBC, and locally advanced or metastatic urothelial cancer and cervical cancer
Phase 1b Dose Expansion in MSS CRC
EXPERIMENTALPatients with histologically confirmed MSS CRC, known KRAS WT, and must have been previously treated with \> = 2 lines of systemic therapy including a fluoropyrimidine, irinotecan, and/or oxaliplatin (and EGFR inhibitor if known Ras wild type)
Interventions
Oral NX-1607
Paclitaxel IV
Eligibility Criteria
You may qualify if:
- Age ≥ 18 years.
- Measurable disease per disease-specific response criteria.
- Patients must have disease that is metastatic or unresectable and have received standard treatment options, are not candidates for standard treatment options, or will otherwise be prevented from receiving any standard treatment options.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Minimum of 3 weeks or 5 half-lives (whichever is shorter) since last dose of systemic cancer therapy (unless otherwise specified) or minimum of 2 weeks since last radiotherapy, or minimum of 6 weeks since last systemic therapy with nitrosoureas, antibody-drug conjugate, or radio immuno-conjugate therapy.
- Adequate organ and bone marrow function, in the absence of growth factors (with limited exception for DLBCL), as defined by laboratory parameters.
- Patients of child-bearing potential must use adequate contraceptive measures to avoid pregnancy for the duration of the study as defined in the protocol.
- Patient must be willing and able to adhere to the prohibitions and restrictions specified in the protocol.
- Each patient must sign an informed consent form (ICF).
- Histological or cytological diagnosis of platinum-resistant EOC, including primary peritoneal and fallopian tube carcinoma; gastric/GEJ cancer; HNSCC; recurrent and either metastatic or unresectable melanoma; NSCLC; mCRPC; MPM; TNBC; locally advanced or metastatic urothelial cancer; cervical cancer; MSS CRC; or DLBCL (including DLBCL-RT)
- Accessible tumor (for all cohorts) or lymph node (DLBCL only) for biopsy (Phase 1b only).
You may not qualify if:
- Active untreated brain metastases.
- Patient has any of the following:
- Uncontrolled intercurrent illness including, but not limited to, poorly controlled hypertension or diabetes, or ongoing active infection requiring systemic therapy.
- Patients with primary refractory EOC defined as patients who do not respond to their first platinum-containing regimen or who relapse less than 6 months after completion of that first platinum-containing regimen
- Psychiatric illness that would limit compliance with study requirements.
- Treatment with any of the following prior to the first dose of NX-1607: CPI (anti-PD-1, PD-L1, cytotoxic T-lymphocyte-associated protein 4, etc) within 3 weeks; autologous or allogeneic stem cell transplant within 100 days; prior systemic cancer therapy within 3 weeks or 5 half-lives (whichever is shorter) (unless otherwise specified) (including hormonal therapy except for hormonal prophylaxis for a prior malignancy); prior radiotherapy within 2 weeks; prior systemic therapy with nitrosoureas, antibody-drug conjugate, or radio-immuno-conjugate therapy within 6 weeks; use of strong or moderate CYP3A4 inducers or inhibitors within 14 days or 7 days, respectively, or 5 half-lives (whichever is longer)
- History of CAR-T therapy within 30 days prior to the first dose of NX-1607.
- Toxicities from previous anti-cancer therapies that have not resolved to baseline levels or to Grade 1 or less except for Grade 2 alopecia and Grade 2 peripheral neuropathy or patients receiving endocrine replacement therapy
- Patients who experienced Grade 3 or higher irAEs with prior immunotherapy.
- History of uveitis, or an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
- Unable to swallow capsules or has malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction likely to interfere with the delivery, absorption, or metabolism of NX-1607.
- Known allergies, hypersensitivity, or intolerance to components of NX-1607.
- Pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 6 months after the last dose of NX-1607.
- Patient is a man who plans to father a child while enrolled in this study or within 3 months after the last dose of NX-1607 and, as applicable, within 6 months after the last dose of paclitaxel.
- Patient has had major surgery (e.g., requiring general anesthesia) within 4 weeks before the planned first dose of NX-1607, or will not have fully recovered from surgery, or has surgery planned during the time the patient is expected to participate in the study or within 4 weeks after the last dose of NX-1607. Note: Patients with minor planned surgical procedures to be conducted under local anesthesia may participate.
- +19 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (17)
City of Hope
Duarte, California, 91010, United States
University of Southern California
Los Angeles, California, 90007, United States
University of California, San Francisco
San Francisco, California, 94158, United States
University of Colorado School of Medicine
Aurora, Colorado, 80045, United States
University of Chicago
Chicago, Illinois, 60637, United States
University of North Carolina
Chapel Hill, North Carolina, 27599, United States
University of Oklahoma
Oklahoma City, Oklahoma, 73104, United States
MD Anderson Cancer Center
Houston, Texas, 77030, United States
University of Virginia
Charlottesville, Virginia, 22908, United States
Fred Hutchinson Cancer Center
Seattle, Washington, 98109, United States
Royal Marsden Hospital NHS Foundation Trust
Sutton, Surrey, SM2 5PT, United Kingdom
Addenbrookes Cambridge University Hospital
Cambridge, CB2 0QQ, United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, G12 0YN, United Kingdom
Sarah Cannon Research Institute
London, W1G 6AD, United Kingdom
The Christie NHS Foundation Trust
Manchester, M20 4BX, United Kingdom
Northern Centre for Cancer Care
Newcastle, NE7 7DN, United Kingdom
Churchill Hospital
Oxford, OX3 7LE, United Kingdom
Related Publications (1)
Wolf D, Baier G. IFNgamma Helps CBLB-Deficient CD8+ T Cells to Put Up Resistance to Tregs. Cancer Immunol Res. 2022 Apr 1;10(4):370. doi: 10.1158/2326-6066.CIR-22-0080.
PMID: 35362047DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Linda Neuman, MD
Nurix Therapeutics, Inc.
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 22, 2021
First Posted
November 4, 2021
Study Start
September 29, 2021
Primary Completion (Estimated)
August 31, 2026
Study Completion (Estimated)
February 28, 2028
Last Updated
September 9, 2025
Record last verified: 2025-09
Data Sharing
- IPD Sharing
- Will not share