Clinical trial NCT06334432: Safety and Efficacy Study of NUV-1511 in Adult Patients With Advanced Solid Tumors
Official title: A Phase 1/2, First-in-Human, Safety and Efficacy Study of NUV-1511 in Adult Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
HER2-negative Breast Cancer
Metastatic Castration-resistant Prostate Cancer (mCRPC)
Pancreatic Cancer
Platinum-resistant Ovarian Cancer (PROC)
Lead sponsor: Nuvation Bio Inc.
Sponsor class: INDUSTRY
First posted: 2024-03-28
Enrollment: 466
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: NUV-1511-01 is a first-in human, open- label, Phase 1/2 to evaluate the safety and efficacy of NUV-1511 in patients with advanced solid tumors. The Phase 1 portion include patients with advanced solid tumors and is designed to determine the safety and the tolerability of doses of NUV-1511. In Phase 2, NUV-1511 will be given to determine the efficacy of patients with advanced solid tumors.


Eligibility criteria: Inclusion Criteria:

* Phase 1 Dose Escalation cohorts, Phase 1 Backfill cohorts, and Phase 2 Tumor Type-Specific cohort(s): must meet one of the following criteria:
* HER2- metastatic breast cancer:

  1. Hormone refractory hormone receptor positive metastatic breast cancer with progression on or after treatment with CDK4/6 inhibitor plus at least one line of systemic chemotherapy in the advanced setting
  2. Triple negative metastatic breast cancer with progression after at one line of systemic chemotherapy in the advanced setting.
* Patients with advanced solid tumors that progressed on or following treatment with Enhertu and/or Trodelvy per label
* mCRPC: Histologically confirmed, metastatic castration resistant adenocarcinoma of the prostate

  1. May have received up to 2 prior chemotherapies in mCRPC setting
  2. Prior therapy with PARP (poly-ADP ribose polymerase) inhibitor, PLUVICTO, Radium-223, or Provenge is allowed
* Pancreatic cancer: PDAC (pancreatic ductal adenocarcinoma) with progression on or after treatment with at least one line of systemic chemotherapy in the advanced setting.
* PROC: Histologically or cytologically confirmed platinum-resistant high-grade serous ovarian, fallopian, or primary peritoneal cancer;
* Phase 1 Dose Escalation cohorts, Phase 1 Backfill cohorts, and Phase 2 Tumor Type-Specific cohorts (except mCRPC; see inclusion criterion 2 above): must have measurable disease per RECIST 1.1
* Phase 2 All Comers cohort: Patients with advanced solid tumors that have progressed during or after treatment with approved therapies or for whom there is no standard effective therapy available.
* Adequate bone marrow and organ function.
* Provide informed consent, which includes compliance with protocol-specified requirements and restrictions

Exclusion Criteria:

* Chemotherapy, hormonal therapy (with the exception of ongoing luteinizing hormone-releasing hormone analogs in male patients and premenopausal females), radiation therapy, or biological anticancer therapy within 14 days before the first dose of study treatment
* Treatment with an investigational agent for any indication within 14 days before the first dose of study treatment for non-myelosuppressive agent, or within 21 days or \<5 half-lives before the first dose of study treatment, whichever is longer, for a myelosuppressive agent
* Ongoing or active infection requiring systemic therapy, or an infection requiring hospitalization or intravenous therapy within 2 weeks before the first dose of study treatment
* Resting left ventricular ejection fraction (LVEF) of \<50% obtained by echocardiography or multigated acquisition scan (MUGA)
* History of significant cardiac disease, including myocardial infarction, New York Heart Association Class II/III/IV heart failure, unstable angina, unstable cardiac arrhythmias (eg, ventricular tachycardia, ventricular fibrillation), syncope of cardiovascular etiology, or cardiac arrest:
* Known immunosuppressive disease or active systemic autoimmune disease such as systemic lupus erythematosus, human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infections not currently controlled by current disease-specific therapy. The following exceptions apply:
* Major surgical procedure within 2 weeks before the first dose of study treatment, or an anticipated need for major surgery during the course of the study
* Other cancer within 2 years before the first dose of study treatment with metastatic or local recurrence potential that could negatively impact survival and/or potentially confound tumor response assessments. Patients with a history of other cancers in the past 2 years should be discussed with the Medical Monitor.
* Female patients who are pregnant or breastfeeding

Primary outcomes:
measure: Phase 1: Assess safety and tolerability of NUV-1511 in advanced solid tumors
timeFrame: First 28 days of dosing (DLT evaluation period)
measure: Phase 1: Identify recommended dosing schedule(s) and corresponding Phase 2 dose(s) (RP2D(s))
timeFrame: First 28 days of dosing (DLT evaluation period)
measure: Phase 2: Evaluate the efficacy of NUV-1511 in advanced solid tumors and selected tumor type(s)
timeFrame: From date of enrollment to date of disease progression, withdrawal of consent, or initiation of subsequent anticancer treatment or up to a period of 5 years, whichever occurs first
measure: Phase 2: Confirm the optimal NUV-1511 dose level/schedule for further development
timeFrame: Periodic efficacy assessments from date of enrollment to date of disease progression, withdrawal of consent, or initiation of subsequent anticancer treatment or up to a period of 5 years, whichever occurs first
measure: Phase 2: Confirm the optimal NUV-1511 target tumor types for further development
timeFrame: Periodic efficacy assessments from date of enrollment to date of disease progression, withdrawal of consent, or initiation of subsequent anticancer treatment or up to a period of 5 years, whichever occurs first
Secondary outcomes:
measure: Phase 1: Explore preliminary efficacy of NUV-1511
timeFrame: From date of enrollment to date of disease progression, withdrawal of consent, or initiation of subsequent anticancer treatment or up to a period of 5 years, whichever occurs first
measure: Phase 1: Explore preliminary efficacy of NUV-1511
timeFrame: From date of enrollment to date of disease progression, withdrawal of consent, or initiation of subsequent anticancer treatment or up to a period of 5 years, whichever occurs first
measure: Phase 1: Explore preliminary efficacy of NUV-1511
timeFrame: From date of enrollment to date of disease progression, withdrawal of consent, or initiation of subsequent anticancer treatment or up to a period of 5 years, whichever occurs first
measure: Characterize the PK profile of NUV-1511
timeFrame: Periodic PK sample collection from date of enrollment to date of disease progression, withdrawal of consent, or initiation of subsequent anticancer treatment or up to a period of 5 years, whichever occurs first.
measure: Characterize the PK profile of NUV-1511
timeFrame: Periodic PK sample collection from date of enrollment to date of disease progression, withdrawal of consent, or initiation of subsequent anticancer treatment or up to a period of 5 years, whichever occurs first.
measure: Phase 2: Further evaluate the safety and efficacy of NUV-1511
timeFrame: Ongoing monitoring of safety and efficacy from date of enrollment to date of disease progression, withdrawal of consent, or initiation of subsequent anticancer treatment or up to a period of 5 years, whichever occurs first
measure: Phase 2: Further evaluate the safety and efficacy of NUV-1511
timeFrame: Ongoing monitoring of safety and efficacy from date of enrollment to date of disease progression, withdrawal of consent, or initiation of subsequent anticancer treatment or up to a period of 5 years, whichever occurs first
measure: Phase 2: Further evaluate the safety and efficacy of NUV-1511
timeFrame: Ongoing monitoring of safety and efficacy from date of enrollment to date of disease progression, withdrawal of consent, or initiation of subsequent anticancer treatment or up to a period of 5 years, whichever occurs first
measure: Phase 2: Further evaluate the safety and efficacy of NUV-1511
timeFrame: Ongoing monitoring of safety and efficacy from date of enrollment to date of disease progression, withdrawal of consent, or initiation of subsequent anticancer treatment or up to a period of 5 years, whichever occurs first
measure: Phase 2: Further evaluate the safety and efficacy of NUV-1511
timeFrame: Ongoing monitoring of safety and efficacy from date of enrollment to date of disease progression, withdrawal of consent, or initiation of subsequent anticancer treatment or up to a period of 5 years, whichever occurs first
measure: Phase 2: Further evaluate the safety and efficacy of NUV-1511
timeFrame: Ongoing monitoring of safety and efficacy from date of enrollment to date of disease progression, withdrawal of consent, or initiation of subsequent anticancer treatment or up to a period of 5 years, whichever occurs first
measure: Phase 2: Further evaluate the safety and efficacy of NUV-1511
timeFrame: Ongoing monitoring of safety and efficacy from date of enrollment to date of disease progression, withdrawal of consent, or initiation of subsequent anticancer treatment or up to a period of 5 years, whichever occurs first
measure: Phase 2: Further evaluate the safety and efficacy of NUV-1511
timeFrame: Ongoing monitoring of safety and efficacy from date of enrollment to date of disease progression, withdrawal of consent, or initiation of subsequent anticancer treatment or up to a period of 5 years, whichever occurs first
measure: Phase 2: Further evaluate the safety and efficacy of NUV-1511
timeFrame: Ongoing monitoring of safety and efficacy from date of enrollment to date of disease progression, withdrawal of consent, or initiation of subsequent anticancer treatment or up to a period of 5 years, whichever occurs first
measure: Phase 2: Further evaluate the safety and efficacy of NUV-1511
timeFrame: Ongoing monitoring of safety and efficacy from date of enrollment to date of disease progression, withdrawal of consent, or initiation of subsequent anticancer treatment or up to a period of 5 years, whichever occurs first
Other outcomes:
measure: Phase 1 and Phase 2: Evaluate biomarkers potentially related to NUV-1511 anti-tumor activity via ctDNA and tumor tissue analysis
timeFrame: Ongoing monitoring of safety and efficacy from date of enrollment to date of disease progression, withdrawal of consent, or initiation of subsequent anticancer treatment or up to a period of 5 years, whichever occurs first
measure: Phase 1 and Phase 2: Evaluate biomarkers potentially related to NUV-1511 anti-tumor activity via ctDNA and tumor tissue analysis
timeFrame: Ongoing monitoring of safety and efficacy from date of enrollment to date of disease progression, withdrawal of consent, or initiation of subsequent anticancer treatment or up to a period of 5 years, whichever occurs first
measure: Phase 1 and Phase 2: Evaluate biomarkers potentially related to NUV-1511 anti-tumor activity
timeFrame: Ongoing monitoring of safety and efficacy from date of enrollment to date of disease progression, withdrawal of consent, or initiation of subsequent anticancer treatment or up to a period of 5 years, whichever occurs first
measure: Phase 1 and Phase 2: Evaluate biomarkers potentially related to NUV-1511 anti-tumor activity
timeFrame: Ongoing monitoring of safety and efficacy from date of enrollment to date of disease progression, withdrawal of consent, or initiation of subsequent anticancer treatment or up to a period of 5 years, whichever occurs first
measure: Phase 1 and Phase 2: Evaluate biomarkers potentially related to NUV-1511 anti-tumor activity
timeFrame: Ongoing monitoring of safety and efficacy from date of enrollment to date of disease progression, withdrawal of consent, or initiation of subsequent anticancer treatment or up to a period of 5 years, whichever occurs first
measure: Phase 1 and Phase 2: Explore pharmacogenetic profiling that may be potentially predictive of NUV-1511 antitumor activity or toxicity
timeFrame: Blood and tumor biopsy collection at the time of enrollment
measure: Phase 1 and Phase 2: Explore pharmacogenetic profiling that may be potentially predictive of NUV-1511 antitumor activity or toxicity
timeFrame: Blood and tumor biopsy collection at the time of enrollment
measure: Phase 1 and Phase 2: Explore pharmacogenetic profiling that may be potentially predictive of NUV-1511 antitumor activity or toxicity
timeFrame: Blood and tumor biopsy collection at the time of enrollment
measure: Evaluate drug exposure-response relationship
timeFrame: Periodic PK sample collection through disease progression, withdrawal of consent, or initiation of subsequent anticancer treatment or up to a period of 5 years, whichever occurs first
measure: Evaluate drug exposure-response relationship
timeFrame: Periodic PK sample collection through disease progression, withdrawal of consent, or initiation of subsequent anticancer treatment or up to a period of 5 years, whichever occurs first
Locations:
city: Detroit
country: United States
facility: Karmanos Cancer Center
state: Michigan
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Huntersville
country: United States
facility: Carolina BioOncology Institute
state: North Carolina
city: Irving
country: United States
facility: NEXT Oncology
state: Texas
city: Salt Lake City
country: United States
facility: START Mountain
state: Utah
city: Fairfax
country: United States
facility: NEXT Oncology
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson
state: Washington
Study officials:
References: