Safety and Efficacy Study of NUV-1511 in Adult Patients With Advanced Solid Tumors

A Phase 1/2, First-in-Human, Safety and Efficacy Study of NUV-1511 in Adult Patients With Advanced Solid Tumors

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.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Cancer; Advanced Solid Tumor; HER2-negative Breast Cancer; Metastatic Castration-resistant Prostate Cancer (mCRPC); Platinum-resistant Ovarian Cancer (PROC)
• Intervention / Treatment: Drug: NUV-1511

• Study Type: Interventional
• Enrollment (Estimated): 466
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Nuvation Bio; Phone Number: 332-208-6102; Email: clinicaltrials@nuvationbio.com

Study Locations

• United States
  • Texas
    • Irving, Texas, United States, 75038
      • Recruiting
      • NEXT Oncology
      • Contact: Naga Koteswari Cheedella; Phone Number: 214-645-4673; Email: ncheedella@nextoncology.com
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • Recruiting
      • START Mountain
      • Contact: William McKean; Phone Number: 801-581-2121; Email: William.McKean@hci.utah.edu
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • NEXT Oncology
      • Contact: Alex Spira; Phone Number: 210-580-9500; Email: aspira@nextoncology.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Phase 1: Schedule A; Schedule A evaluating escalating dose levels of NUV-1511	Drug: NUV-1511; Novel small molecule
Other: Phase 1: Schedule B; Schedule B evaluating escalating dose levels of NUV-1511	Drug: NUV-1511; Novel small molecule
Experimental: Phase 2: Tumor Type 1; Tumor type to be selected after Phase 1. Dose Schedules A and B to be further evaluated.	Drug: NUV-1511; Novel small molecule
Experimental: Phase 2: Tumor Type 2; Tumor type to be selected after Phase 1. Dose level and schedule to be selected after identification of the recommended phase 2 dose (RP2D) in Phase 1.	Drug: NUV-1511; Novel small molecule
Experimental: Phase 2: All comers; All tumor types allowed per protocol. Dose level and schedule to be selected after identification of the recommended phase 2 dose (RP2D) in Phase 1.	Drug: NUV-1511; Novel small molecule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Assess safety and tolerability of NUV-1511 in advanced solid tumors	Number of patients with dose limiting toxicities, treatment emergent adverse events (TEAE) and serious adverse events (SAE) and laboratory abnormalities	First 28 days of dosing (DLT evaluation period)
Phase 1: Identify recommended dosing schedule(s) and corresponding Phase 2 dose(s) (RP2D(s))	Number of patients with DLTs, TEAEs and SAEs and laboratory abnormalities	First 28 days of dosing (DLT evaluation period)
Phase 2: Evaluate the efficacy of NUV-1511 in advanced solid tumors and selected tumor type(s)	Efficacy measures may include tumor assessments, as assessed by CT scans, PET/CT, whole body bone scan and MRI	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
Phase 2: Confirm the optimal NUV-1511 dose level/schedule for further development	Overall response rate per RECIST 1.1 (Composite response rate for mCRPC patients only, if enrolled in Phase 2)	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
Phase 2: Confirm the optimal NUV-1511 target tumor types for further development	Overall response rate per RECIST 1.1 (Composite response rate for mCRPC patients only, if enrolled in Phase 2)	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Explore preliminary efficacy of NUV-1511	Overall response rate and duration of response per RECIST 1.1. Efficacy measures may include tumor assessments, as assessed by CT scans, PET/CT, whole body bone scan and MRI.	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
Phase 1: Explore preliminary efficacy of NUV-1511	Overall response rate and duration of response per composite response rate (for mCRPC). Efficacy measures may include tumor assessments, as assessed by CT scans, PET/CT, whole body bone scan and MRI.	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
Phase 1: Explore preliminary efficacy of NUV-1511	Overall response rate and duration of response per response rates in specific disease markers. Efficacy measures may include tumor assessments, as assessed by CT scans, PET/CT, whole body bone scan and MRI.	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
Characterize the PK profile of NUV-1511	Parameters include, but not limited to, maximum observed plasma concentration (Cmax)	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.
Characterize the PK profile of NUV-1511	Parameters include, but not limited to, area under the plasma concentration-time curve (AUC)	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.
Phase 2: Further evaluate the safety and efficacy of NUV-1511	Incidence of TEAEs and SAEs	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
Phase 2: Further evaluate the safety and efficacy of NUV-1511	Laboratory abnormalities	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
Phase 2: Further evaluate the safety and efficacy of NUV-1511	Duration of response	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
Phase 2: Further evaluate the safety and efficacy of NUV-1511	Clinical best response	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
Phase 2: Further evaluate the safety and efficacy of NUV-1511	Progression free survival	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
Phase 2: Further evaluate the safety and efficacy of NUV-1511	Overall survival	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
Phase 2: Further evaluate the safety and efficacy of NUV-1511	PK exposure-response modeling, which includes measuring plasma concentration versus overall response rate	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
Phase 2: Further evaluate the safety and efficacy of NUV-1511	PK exposure-response modeling, which includes measuring plasma concentration versus progression free survival	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
Phase 2: Further evaluate the safety and efficacy of NUV-1511	PK exposure-response modeling, which includes measuring plasma concentration versus treatment emergent adverse events and serious adverse events.	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
Phase 2: Further evaluate the safety and efficacy of NUV-1511	Response rates in disease-specific markers	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1 and Phase 2: Evaluate biomarkers potentially related to NUV-1511 anti-tumor activity via ctDNA and tumor tissue analysis	Blood sample for exploratory analysis of circulating DNA	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
Phase 1 and Phase 2: Evaluate biomarkers potentially related to NUV-1511 anti-tumor activity via ctDNA and tumor tissue analysis	Blood sample for exploratory analysis of gene expression (including that of hormone receptors and efflux transporters)	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
Phase 1 and Phase 2: Evaluate biomarkers potentially related to NUV-1511 anti-tumor activity	Tumor biopsy for exploratory analysis of tumor genome	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
Phase 1 and Phase 2: Evaluate biomarkers potentially related to NUV-1511 anti-tumor activity	Tumor biopsy for exploratory analysis of epigenome	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
Phase 1 and Phase 2: Evaluate biomarkers potentially related to NUV-1511 anti-tumor activity	Tumor biopsy for exploratory analysis of gene expression	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
Phase 1 and Phase 2: Explore pharmacogenetic profiling that may be potentially predictive of NUV-1511 antitumor activity or toxicity	Identification of genetic factors that predict toxicity	Blood and tumor biopsy collection at the time of enrollment
Phase 1 and Phase 2: Explore pharmacogenetic profiling that may be potentially predictive of NUV-1511 antitumor activity or toxicity	Identification of genetic factors that predict anti-tumor activity	Blood and tumor biopsy collection at the time of enrollment
Phase 1 and Phase 2: Explore pharmacogenetic profiling that may be potentially predictive of NUV-1511 antitumor activity or toxicity	Identification of genetic factors that predict metabolism of NUV-1511	Blood and tumor biopsy collection at the time of enrollment
Evaluate drug exposure-response relationship	PK exposure response modeling which includes measuring PK exposure versus efficacy	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
Evaluate drug exposure-response relationship	PK exposure response modeling which includes measuring PK exposure versus safety	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

Collaborators and Investigators

• Sponsor: Nuvation Bio Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: February 12, 2024
• First Submitted That Met QC Criteria: March 20, 2024
• First Posted (Actual): March 28, 2024

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: NUV-1511-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No