RECRUITING

A Study of NX-1607 in Adults With Advanced Malignancies

Conditions

Ovarian Cancer, Epithelial Gastric Cancer GastroEsophageal Junction (GEJ) Cancer Head and Neck Squamous Cell Carcinoma 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)Metastatic Urothelial Carcinoma Cervical Cancer Diffuse Large B Cell Lymphoma (DLBCL)Richter Transformation Microsatellite Stable Colorectal Carcinoma Ubiquitin Ligase Inhibitor Advanced Malignancies T-cell Activation

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2021-09-29

Study Completion:2026-02-28

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05107674

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* 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).	* 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. * Vaccinated with a live vaccine within 28 days (with the exception of the annual inactivated influenza vaccine) or COVID-19 vaccination within 14 days prior to the first dose of NX-1607. * 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 PSA \< 10 ng/mL. * Any other cancer from which the patient has been disease-free for ≥ 2 years. * 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 hepatitis, including hepatitis A (hepatitis A virus immunoglobulin M \[IgM\] positive), hepatitis B (hepatitis B virus \[HBV\] surface antigen positive), or hepatitis C (hepatitis C virus \[HCV\] antibody positive, confirmed by HCV RNA). Patients with HCV with undetectable virus after treatment are eligible. Patients with prior exposure to HBV may be entered if quantitative PCR is negative. * Use of systemic corticosteroids (\> 20 mg prednisone or equivalent) within 15 days (except for prophylaxis for radio diagnostic contrast reactions and/or prophylaxis for patients receiving paclitaxel), or other immunosuppressive drugs within 30 days, prior to the first dose of NX-1607. * Use of biotin (i.e., Vitamin B7) or supplements containing biotin higher than the daily adequate intake of 30 µg \[NIH 2020\] (Note: Patients who switch from a high dose to a dose of 30 µg/day or less at least 1 day prior to Screening assessments are eligible for study entry). * Receipt of an IP or has been treated with an investigational device within 3 weeks or 5 half-lives (whichever is shorter) prior to the first dose of NX-1607. * Any of the following within 6 months prior to the first dose of NX-1607 or ongoing: * Myocardial infarction * Unstable angina * Unstable symptomatic ischemic heart disease * New York Heart Association Class III or IV heart failure * Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events) * Any other significant cardiac condition (e.g., pericardial effusion, restrictive cardiomyopathy, severe untreated valvular stenosis, or severe congenital heart disease) * Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating Investigator in consultation with the Medical Monitor.

Inclusion Criteria

Exclusion Criteria

* 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).

* 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.
* Vaccinated with a live vaccine within 28 days (with the exception of the annual inactivated influenza vaccine) or COVID-19 vaccination within 14 days prior to the first dose of NX-1607.
* 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 PSA \< 10 ng/mL.
* Any other cancer from which the patient has been disease-free for ≥ 2 years.
* 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 hepatitis, including hepatitis A (hepatitis A virus immunoglobulin M \[IgM\] positive), hepatitis B (hepatitis B virus \[HBV\] surface antigen positive), or hepatitis C (hepatitis C virus \[HCV\] antibody positive, confirmed by HCV RNA). Patients with HCV with undetectable virus after treatment are eligible. Patients with prior exposure to HBV may be entered if quantitative PCR is negative.
* Use of systemic corticosteroids (\> 20 mg prednisone or equivalent) within 15 days (except for prophylaxis for radio diagnostic contrast reactions and/or prophylaxis for patients receiving paclitaxel), or other immunosuppressive drugs within 30 days, prior to the first dose of NX-1607.
* Use of biotin (i.e., Vitamin B7) or supplements containing biotin higher than the daily adequate intake of 30 µg \[NIH 2020\] (Note: Patients who switch from a high dose to a dose of 30 µg/day or less at least 1 day prior to Screening assessments are eligible for study entry).
* Receipt of an IP or has been treated with an investigational device within 3 weeks or 5 half-lives (whichever is shorter) prior to the first dose of NX-1607.
* Any of the following within 6 months prior to the first dose of NX-1607 or ongoing:
* Myocardial infarction
* Unstable angina
* Unstable symptomatic ischemic heart disease
* New York Heart Association Class III or IV heart failure
* Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events)
* Any other significant cardiac condition (e.g., pericardial effusion, restrictive cardiomyopathy, severe untreated valvular stenosis, or severe congenital heart disease)
* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating Investigator in consultation with the Medical Monitor.

Contacts and Locations

Study Contact

Nurix Therapeutics Patient Outreach

CONTACT

4152307815

nx1607101@nurixtx.com

Principal Investigator

Paula O'Connor, MD

STUDY_DIRECTOR

Nurix Therapeutics, Inc.

Study Locations (Sites)

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

Memorial Sloan Kettering Cancer Center

New York, New York, 10021

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

Swedish Cancer Institute

Seattle, Washington, 98104

United States

Fred Hutchinson Cancer Center

Seattle, Washington, 98109

United States

Collaborators and Investigators

Sponsor: Nurix Therapeutics, Inc.

Paula O'Connor, MD, STUDY_DIRECTOR, Nurix Therapeutics, Inc.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-09-29

Study Completion Date2026-02-28

Study Record Updates

Study Start Date2021-09-29

Study Completion Date2026-02-28

Terms related to this study

Keywords Provided by Researchers

Ubiquitin Ligase Inhibitor
Advanced Malignancies
T-cell Activation

Additional Relevant MeSH Terms

Ovarian Cancer, Epithelial
Gastric Cancer
GastroEsophageal Junction (GEJ) Cancer
Head and Neck Squamous Cell Carcinoma
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)
Metastatic Urothelial Carcinoma
Cervical Cancer
Diffuse Large B Cell Lymphoma (DLBCL)
Richter Transformation
Microsatellite Stable Colorectal Carcinoma