Trial Title:
A Study of NX-1607 in Adults With Advanced Malignancies
NCT ID:
NCT05107674
Condition:
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
Conditions: Official terms:
Lymphoma
Carcinoma
Neoplasms
Lymphoma, Large B-Cell, Diffuse
Triple Negative Breast Neoplasms
Mesothelioma
Mesothelioma, Malignant
Squamous Cell Carcinoma of Head and Neck
Colorectal Neoplasms
Carcinoma, Ovarian Epithelial
Paclitaxel
Conditions: Keywords:
Ubiquitin Ligase Inhibitor
Advanced Malignancies
T-cell Activation
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
NX-1607
Description:
Oral NX-1607
Arm group label:
Phase 1a Dose Escalation of NX-1607 (monotherapy)
Arm group label:
Phase 1a Dose Escalation of NX-1607 in combination with Paclitaxel
Arm group label:
Phase 1a Food Effect
Arm group label:
Phase 1b Dose Expansion in DLBCL including DLBCL-RT
Arm group label:
Phase 1b Dose Expansion in HNSCC
Arm group label:
Phase 1b Dose Expansion in MSS CRC
Arm group label:
Phase 1b Dose Expansion in advanced NSCLC
Arm group label:
Phase 1b Dose Expansion in advanced gastric/GEJ cancer
Arm group label:
Phase 1b Dose Expansion in mCRPC
Arm group label:
Phase 1b Dose Expansion in mixed solid tumor cohort
Arm group label:
Phase 1b Dose Expansion in platinum-resistant EOC
Arm group label:
Phase 1b Dose Expansion in recurrent melanoma
Arm group label:
Phase 1b Dose Expansion of NX-1607 in combination with Paclitaxel
Other name:
Cbl-b Inhibitor
Intervention type:
Drug
Intervention name:
Paclitaxel
Description:
Paclitaxel IV
Arm group label:
Phase 1a Dose Escalation of NX-1607 in combination with Paclitaxel
Arm group label:
Phase 1b Dose Expansion of NX-1607 in combination with Paclitaxel
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.
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 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.
Criteria for eligibility:
Criteria:
Key Inclusion 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).
Key Exclusion Criteria:
- 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
City of Hope
Address:
City:
Duarte
Zip:
91010
Country:
United States
Status:
Recruiting
Contact:
Last name:
Dr. Villaflor
Email:
vvillaflor@coh.org
Facility:
Name:
University of Southern California
Address:
City:
Los Angeles
Zip:
90007
Country:
United States
Status:
Recruiting
Contact:
Last name:
Xiomara Menendez
Email:
Xiomara.Menendez@med.usc.edu
Contact backup:
Last name:
Lorraine Martinez
Email:
Lorraine.Martinez@med.usc.edu
Facility:
Name:
University of California, San Francisco
Address:
City:
San Francisco
Zip:
94158
Country:
United States
Status:
Recruiting
Contact:
Last name:
Early Phase Clinical Trials
Email:
earlyphaseclinicaltrials@ucsf.edu
Facility:
Name:
University of Colorado School of Medicine
Address:
City:
Aurora
Zip:
80045
Country:
United States
Status:
Recruiting
Contact:
Last name:
Brandi Asheim
Contact backup:
Email:
BRANDI.ASHEIM@CUANSCHUTZ.EDU
Investigator:
Last name:
Wells Messersmith, MD
Email:
Principal Investigator
Facility:
Name:
University of Chicago
Address:
City:
Chicago
Zip:
60637
Country:
United States
Status:
Recruiting
Contact:
Last name:
Clinical Trials Office
Email:
cancerclinicaltrials@bsd.uchicago.edu
Facility:
Name:
Memorial Sloan Kettering Cancer Center
Address:
City:
New York
Zip:
10021
Country:
United States
Status:
Recruiting
Facility:
Name:
University of North Carolina
Address:
City:
Chapel Hill
Zip:
27599
Country:
United States
Status:
Recruiting
Contact:
Last name:
Clinical Trials Office
Phone:
919-966-4432
Email:
cancerclinicaltrials@med.unc.edu
Facility:
Name:
University of Oklahoma
Address:
City:
Oklahoma City
Zip:
73104
Country:
United States
Status:
Recruiting
Contact:
Last name:
Christina Caldwell
Contact backup:
Email:
Christina-Caldwell@ouhsc.edu
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Rabia Khan
Email:
rkhan@mdanderson.org
Facility:
Name:
University of Virginia
Address:
City:
Charlottesville
Zip:
22908
Country:
United States
Status:
Recruiting
Contact:
Last name:
Magnifique Irakoze
Email:
RVE7XG@uvahealth.org
Facility:
Name:
Swedish Cancer Institute
Address:
City:
Seattle
Zip:
98104
Country:
United States
Status:
Recruiting
Contact:
Last name:
Swathi Namburi
Contact backup:
Email:
swathi.namburi@swedish.org
Investigator:
Last name:
Swathi Namburi, MD
Email:
Principal Investigator
Facility:
Name:
Fred Hutchinson Cancer Center
Address:
City:
Seattle
Zip:
98109
Country:
United States
Status:
Recruiting
Contact:
Last name:
Lia Pagtakhan
Email:
liapagta@fredhutch.org
Facility:
Name:
Royal Marsden Hospital NHS Foundation Trust
Address:
City:
Sutton
Zip:
SM2 5PT
Country:
United Kingdom
Status:
Recruiting
Facility:
Name:
University College London Hospitals NHS Foundation Trust
Address:
City:
Bloomsbury
Zip:
W1T 7HA
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
UCLH Research
Email:
uclh.research@nhs.net
Facility:
Name:
Addenbrookes Cambridge University Hospital
Address:
City:
Cambridge
Zip:
CB2 0QQ
Country:
United Kingdom
Status:
Recruiting
Facility:
Name:
Beatson West of Scotland Cancer Centre
Address:
City:
Glasgow
Zip:
G12 0YN
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Ruth Orr
Contact backup:
Email:
Ruth.Orr@ggc.scot.nhs.uk
Facility:
Name:
Sarah Cannon Research Institute
Address:
City:
London
Zip:
W1G 6AD
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Referrals
Email:
Referrals.SCRI@hcahealthcare.co.uk
Facility:
Name:
The Christie NHS Foundation Trust
Address:
City:
Manchester
Zip:
M20 4BX
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
The Christie Enquiries
Contact backup:
Email:
the-christie.ECMT.enquiries@nhs.net
Facility:
Name:
Northern Centre for Cancer Care
Address:
City:
Newcastle
Zip:
NE7 7DN
Country:
United Kingdom
Status:
Recruiting
Facility:
Name:
Churchill Hospital
Address:
City:
Oxford
Zip:
OX3 7LE
Country:
United Kingdom
Status:
Recruiting
Start date:
September 29, 2021
Completion date:
February 28, 2026
Lead sponsor:
Agency:
Nurix Therapeutics, Inc.
Agency class:
Industry
Source:
Nurix Therapeutics, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05107674
