Ovarian Cancer, EpithelialPhase 1NCT05107674
A Study of NX-1607 in Adults With Advanced Malignancies
A Phase 1 study testing NX-1607 and Paclitaxel in people with Ovarian Cancer, Epithelial and Gastric Cancer, run by Nurix Therapeutics, Inc. at 17 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ovarian Cancer, Epithelial, Gastric Cancer, GastroEsophageal Junction (GEJ) Cancer
- What is being tested?
- NX-1607 and Paclitaxel
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 345 participants
- Where
- 17 sitesin 2 countries
- Study dates
- 29 Sep 2021to 28 Feb 2028
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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).
Who cannot join
- 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)
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- 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.
Trial locations and contacts
17 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
17 sites in 2 countries
United States10 sites, 9 recruiting
- Recruiting
University of Colorado School of Medicine
Aurora, Colorado, 80045
Brandi Asheim
BRANDI.ASHEIM@CUANSCHUTZ.EDU
- Recruiting
University of North Carolina
Chapel Hill, North Carolina, 27599
Clinical Trials Office, 919-966-4432, cancerclinicaltrials@med.unc.edu
- Recruiting
University of Virginia
Charlottesville, Virginia, 22908
Chrystal Axford, CGP9E@uvahealth.org
- Recruiting
University of Chicago
Chicago, Illinois, 60637
Clinical Trials Office, cancerclinicaltrials@bsd.uchicago.edu
- Completed
City of Hope
Duarte, California, 91010
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
Rabia Khan, rkhan@mdanderson.org
- Recruiting
University of Southern California
Los Angeles, California, 90007
Xiomara Menendez, Xiomara.Menendez@med.usc.edu
Lorraine Martinez, Lorraine.Martinez@med.usc.edu
- Recruiting
University of Oklahoma
Oklahoma City, Oklahoma, 73104
Christina Caldwell
Christina-Caldwell@ouhsc.edu
- Recruiting
University of California, San Francisco
San Francisco, California, 94158
Early Phase Clinical Trials, earlyphaseclinicaltrials@ucsf.edu
- Recruiting
Fred Hutchinson Cancer Center
Seattle, Washington, 98109
Phase 1 Research Program, phase1clinicaltrial@fredhutch.org
United Kingdom7 sites, 6 recruiting
- Recruiting
Addenbrookes Cambridge University Hospital
Cambridge, CB2 0QQ
- Recruiting
Beatson West of Scotland Cancer Centre
Glasgow, G12 0YN
Ruth Orr
Ruth.Orr@ggc.scot.nhs.uk
- Recruiting
Sarah Cannon Research Institute
London, W1G 6AD
Referrals, Referrals.SCRI@hcahealthcare.co.uk
- Recruiting
The Christie NHS Foundation Trust
Manchester, M20 4BX
The Christie Enquiries
the-christie.ECMT.enquiries@nhs.net
- Recruiting
Northern Centre for Cancer Care
Newcastle, NE7 7DN
- Completed
Churchill Hospital
Oxford, OX3 7LE
- Recruiting
Royal Marsden Hospital NHS Foundation Trust
Sutton, Surrey, SM2 5PT
About this study
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
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.
Read the detailed description
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.
- 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)
- Being tested
- NX-1607, Paclitaxel
- Keywords
- Ubiquitin Ligase Inhibitor, Advanced Malignancies, T-cell Activation
- Medical subject headings
- Carcinoma, Ovarian Epithelial, Stomach Neoplasms, Neoplasms, Squamous Cell Carcinoma of Head and Neck, Neoplasm Metastasis, Carcinoma, Non-Small-Cell Lung, Mesothelioma, Malignant, Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NX-1607Drug
Also called Cbl-b Inhibitor
Oral NX-1607
PaclitaxelDrug
Paclitaxel IV
| Study group | Role | What they receive |
|---|---|---|
| Phase 1a Dose Escalation of NX-1607 (monotherapy) | Experimental | Multiple dose levels and dosing regimen of NX-1607 to be evaluated; determination of MTD/Phase 1b recommended dose. Receives: Drug: NX-1607 |
| Phase 1a Food Effect | Experimental | Impact of food on NX-1607 bioavailability and tolerability to be evaluated Receives: Drug: NX-1607 |
| Phase 1b Dose Expansion in platinum-resistant EOC | Experimental | Patients with platinum-resistant EOC, including primary peritoneal and fallopian tube carcinoma Receives: Drug: NX-1607 |
| Phase 1b Dose Expansion in advanced gastric/GEJ cancer | Experimental | Patients with recurrent, locally advanced, or metastatic gastric or GEJ adenocarcinoma Receives: Drug: NX-1607 |
| Phase 1b Dose Expansion in HNSCC | Experimental | Patients with recurrent, locally advanced, or metastatic HNSCC Receives: Drug: NX-1607 |
| Phase 1b Dose Expansion in recurrent melanoma | Experimental | Patients with recurrent and either metastatic or unresectable Melanoma Receives: Drug: NX-1607 |
| Phase 1b Dose Expansion in advanced NSCLC | Experimental | Patients with Stage IV NSCLC Receives: Drug: NX-1607 |
| Phase 1b Dose Expansion in mCRPC | Experimental | Patients 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 Receives: Drug: NX-1607 |
| Phase 1b Dose Expansion in mixed solid tumor cohort | Experimental | Cohort of mixed solid tumor indications consisting of patients with MPM, TNBC, locally advanced or metastatic urothelial cancer, cervical cancer, or DLBCL/DLBCL-RT Receives: Drug: NX-1607 |
| Phase 1a Dose Escalation of NX-1607 in combination with Paclitaxel | Experimental | Indications 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. Receives: Drug: NX-1607; Drug: Paclitaxel |
| Phase 1b Dose Expansion of NX-1607 in combination with Paclitaxel | Experimental | Indications 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 Receives: Drug: NX-1607; Drug: Paclitaxel |
| Phase 1b Dose Expansion in MSS CRC | Experimental | Patients 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) Receives: Drug: NX-1607 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 16 months
Incidence of immune-related AEs (irAEs), all deaths, and dose-limiting toxicities (DLTs)
Phase 1a
Measured: Up to 2 Years
Objective Response Rate (ORR) per disease-specific response criteria as assessed by the Investigator
Phase 1b
Measured: Up to 3 Years
Secondary outcomes (17)
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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Up to 3 Years
Objective response rate (ORR) per disease-specific response criteria as assessed by the Investigator
Phase 1a
Measured: Up to 3 Years
Duration of response (DOR) as assessed by the Investigator
Phase 1a/1b
Measured: Up to 3 Years
Disease control rate (DCR) as assessed by the Investigator
Phase 1a/1b
Measured: Up to 3 Years
Progression-free survival (PFS) as assessed by the Investigator
Phase 1a/1b
Measured: Up to 3 Years
Overall survival (OS) as assessed by the Investigator
Phase 1a/1b
Measured: 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
Measured: Up to 3 Years
Time to disease progression assessed by the Investigator (according to relevant disease histology)
Phase 1b
Measured: Up to 3 Years
Incidence of IrAEs and all deaths
Phase 1b
Measured: Up to 3 Years
Time from start of treatment to disease progression based on PCWG3 criteria
Phase 1b (mCRPC cohort only)
Measured: Up to 3 Years
PD Biomarkers: Changes from baseline in tumor tissue biopsies of immune cell infiltration or other histological features
Phase 1b
Measured: Up to 3 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2021
- Study start29 Sep 2021
- Primary completion31 Aug 2026 (estimated)
- Study completion28 Feb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ovarian Cancer, EpithelialStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 345 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nurix Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Linda Neuman, MD, Study director, Nurix Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05107674
- Sponsor's protocol ID
- NX-1607-101
- Status last verified
- Sep 2025
- First submitted
- 22 Sep 2021
- Last updated
- 9 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 35362047