RECRUITING

NP-G2-044 as Monotherapy and Combination Therapy in Patients With Advanced or Metastatic Solid Tumor Malignancies

Conditions

Advanced or Metastatic Solid Tumor Malignancies

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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

Multicenter, open-label study in patients with advanced or metastatic solid tumor malignancies to evaluate the safety, tolerability, and preliminary anti-tumor efficacy, PK, and pharmacodynamics of continuously dosed NP-G2-044 monotherapy and NP-G2-044 in combination with anti-PD-1 therapy.

Official Title

NP-G2-044 as Monotherapy and Combination Therapy in Patients With Advanced or Metastatic Solid Tumor Malignancies

Quick Facts

Study Start:2021-12-07

Study Completion:2025-09

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05023486

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
1. Male or female ≥18 years of age; 2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1; 3. Life expectancy of \> 6 months; 4. Abilty to swallow capsules and tablets; 5. Adequate organ and bone marrow function, defined by the following: 6. Female patients of childbearing potential must have a negative serum or urine pregnancy test at Screening and within 24 hours (if urine test) or 72 hours (if serum test) before the first dose of NP-G2-044. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required and must be negative for the patient to be eligible; Note: A woman is considered to be childbearing potential unless she is postmenopausal (≥1 year without menses and confirmed with a follicle-stimulating hormone \[FSH\] test) or surgically sterilized via bilateral oophorectomy, hysterectomy, bilateral tubal ligation, or successful Essure® placement with a documented confirmation test at least 3 months after the procedure. 7. Male patients must be surgically sterile or willing to use a highly effective double-barrier contraception method (e.g., male condom with diaphragm or male condom with cervical cap) upon study entry, while on NP-G2-044, and for a period of at least 4 months following the last dose of NP-G2-044; and 8. Able to understand and voluntarily sign a written informed consent form (ICF) and willing and able to comply with protocol requirements. 1. Have a histopathologically confirmed advanced or metastatic solid tumor malignancy for which standard therapies are no longer effective, not tolerated or ineligible for the patient to receive; 2. Have measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1); 3. For monotherapy expansion cohort A (after the Mono-RP2D has been identified), patients must have: 1. Gynecologic malignancies including ovarian, endometrial/uterine, fallopian tube, cervical, vulvar, and vaginal cancers; or 2. Epidermal growth factor receptor (EGFR)-high (2+ or 3+ staining per DAKO criteria or genomic sequencing data showing 3 or more copies of the EGFR gene) triple-negative breast cancer (TNBC). 4. For Monotherapy Expansion Cohort B, patient must have advanced or metastatic solid tumors malignancy 1. Have measurable disease per RECIST 1.1; 2. Patients must meet 1 of the following criteria to enroll in Combination Therapy Expansion Cohort A: 1. Have initiated anti-PD-(L)1 therapy in accordance with the package insert and have been receiving the anti-PD-(L)1 therapy for ≥3 months (with therapy currently ongoing) and have stable disease (defined either by post-treatment onset radiographic scan or ≥3 months without radiographic or clinical evidence of progression), or had an initial period of stable disease and now have an initial scan demonstrating progressive disease per RECIST 1.1. or 2. Have discontinued prior anti-PD-(L)1 therapy and are now eligible for de novo NP-G2-044 plus standard of care anti-PD-1 therapy. 3. Patients must meet 1 of the following criteria to enroll in Combination Therapy Expansion Cohorts B through E: 1. Have initiated anti-PD-(L)1 therapy. in accordance with the package insert and have been receiving the anti-PD-(L)1 therapy for \>3 months (with therapy currently ongoing) and have stable disease (as defined above), or had an initial period of stable disease or response and now have an initial scan demonstrating progressive disease per RECIST 1.1; or 2. Have confirmed progressive disease and discontinued prior anti-PD-(L)1 therapy and are now eligible for de novo NP-G2-044 plus standard of care anti-PD-1 therapy. 4. For Combination Therapy Expansion Cohort B, patients must have cutaneous squamous cell carcinoma (CSCC) (human papilloma virus \[HPV\]-positive or -negative; documentation of HPV status is required); 5. For Combination Therapy Expansion Cohort C, patients must have either: 1. Esophageal squamous cell carcinoma (ESCC) (HPV-positive or -negative; documentation of HPV status is required); or 2. Oropharyngeal squamous cell carcinoma (OPSCC) (HPV-positive or -negative; documentation of HPV status is required). 6. For Combination Therapy Expansion Cohort D, patients must have non muscle invasive bladder cancer (NMIBC) meeting Bacillus Calmette-Guérin (BCG)-unresponsive criteria; 7. For Combination Therapy Expansion Cohort E, patients must have microsatellite instability high (MSI-H) cancer; 8. For Combination Therapy Expansion Cohort F, patients must be immunotherapy naïve (I O naïve), have pancreatic ductal adenocarcinoma (PDAC), and meet the following criteria: 1. Have had stable disease or response with at least 4 months of standard of care chemotherapy; 2. Have no liver metastasis; and 3. Have albumin within the normal range at Screening and \>3.5 g/dL (±10%) 3 days before Cycle 1 Day 1. 9. For Combination Therapy Expansion Cohort G, patients must be I O naïve, have platinum resistant ovarian cancer (PROC), and meet the following criteria: 1. Had disease recurrence during or within 6 months after last administration of platinum-based chemotherapy; and 2. Received no more than 2 prior regimens of systemic therapy after development of platinum resistance.	1. Received chemotherapy or radiotherapy within 4 weeks or 5 half-lives, whichever is shorter, of the first dose of NP-G2-044; Note: Prior immunotherapy is allowed for patients receiving NP-G2-044 monotherapy. For PDAC patients in Combination Therapy Expansion Cohort F: received systemic therapy within 2 weeks of the first dose of NP-G2-044. 2. Unresolved toxicities from previous anti-cancer therapy, defined as toxicities (other than NCI CTCAE v5.0 Grade ≤2 alopecia or neuropathy) not yet resolved to NCI CTCAE v5.0 Grade ≤1; Note: Patients who experienced a Grade ≥3 anti-PD-1-related AE per NCI CTCAE v5.0 are excluded unless recovered and approved by the Novita Medical Monitor or designee. 3. Receiving any other investigational agent(s) or have received an investigational agent within 4 weeks of the first dose of NP-G2-044; Note: Patients who have progressed on NP-G2-044 treatment prior to this study are not eligible 4. Known untreated brain metastases or treated brain metastases that have not been radiographically and clinically stable (i.e., not requiring steroids) ≥4 weeks prior to study enrollment; 5. QTc by Fridericia method \>470 msec or electrocardiogram (ECG) with evidence of clinically meaningful conduction abnormalities or active ischemia as determined by the Investigator; 6. Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, hypertension, unstable angina pectoris, cardiac arrhythmia, autoimmune or inflammatory diseases, or psychiatric illness/social situations that would limit compliance with study requirements; 7. Pregnant, lactating, or is planning to attempt to become pregnant or impregnate someone during the study or within 90 days after dosing of NP-G2-044; 8. Received prior allogenic hematopoietic stem cell transplantation or allogenic bone marrow transplantation; 9. Received prior solid organ transplantation; 10. Ongoing immunosuppressive therapy (≥10 mg/day of prednisone or its equivalent); 11. Requires the use of a strong inhibitor or inducer of cytochrome P450 (CYP)3A4, CYP1A2, or CYP2D6 during the study; 12. History of clinically meaningful gastrointestinal bleeding, intestinal obstruction, or gastrointestinal perforation within 6 months of study enrollment; 13. Excluded by the Sponsor due to medical history, physical examination findings, clinical laboratory results, prior medications, or other entrance criteria; or 14. For PDAC patients in Combination Therapy Expansion Cohort F only: have a documented rise in tumor markers within the last 4 months.

Inclusion Criteria

Exclusion Criteria

1. Male or female ≥18 years of age;
2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;
3. Life expectancy of \> 6 months;
4. Abilty to swallow capsules and tablets;
5. Adequate organ and bone marrow function, defined by the following:
6. Female patients of childbearing potential must have a negative serum or urine pregnancy test at Screening and within 24 hours (if urine test) or 72 hours (if serum test) before the first dose of NP-G2-044. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required and must be negative for the patient to be eligible; Note: A woman is considered to be childbearing potential unless she is postmenopausal (≥1 year without menses and confirmed with a follicle-stimulating hormone \[FSH\] test) or surgically sterilized via bilateral oophorectomy, hysterectomy, bilateral tubal ligation, or successful Essure® placement with a documented confirmation test at least 3 months after the procedure.
7. Male patients must be surgically sterile or willing to use a highly effective double-barrier contraception method (e.g., male condom with diaphragm or male condom with cervical cap) upon study entry, while on NP-G2-044, and for a period of at least 4 months following the last dose of NP-G2-044; and
8. Able to understand and voluntarily sign a written informed consent form (ICF) and willing and able to comply with protocol requirements.
1. Have a histopathologically confirmed advanced or metastatic solid tumor malignancy for which standard therapies are no longer effective, not tolerated or ineligible for the patient to receive;
2. Have measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1);
3. For monotherapy expansion cohort A (after the Mono-RP2D has been identified), patients must have:
1. Gynecologic malignancies including ovarian, endometrial/uterine, fallopian tube, cervical, vulvar, and vaginal cancers; or
2. Epidermal growth factor receptor (EGFR)-high (2+ or 3+ staining per DAKO criteria or genomic sequencing data showing 3 or more copies of the EGFR gene) triple-negative breast cancer (TNBC).
4. For Monotherapy Expansion Cohort B, patient must have advanced or metastatic solid tumors malignancy
1. Have measurable disease per RECIST 1.1;
2. Patients must meet 1 of the following criteria to enroll in Combination Therapy Expansion Cohort A:
1. Have initiated anti-PD-(L)1 therapy in accordance with the package insert and have been receiving the anti-PD-(L)1 therapy for ≥3 months (with therapy currently ongoing) and have stable disease (defined either by post-treatment onset radiographic scan or ≥3 months without radiographic or clinical evidence of progression), or had an initial period of stable disease and now have an initial scan demonstrating progressive disease per RECIST 1.1. or
2. Have discontinued prior anti-PD-(L)1 therapy and are now eligible for de novo NP-G2-044 plus standard of care anti-PD-1 therapy.
3. Patients must meet 1 of the following criteria to enroll in Combination Therapy Expansion Cohorts B through E:
1. Have initiated anti-PD-(L)1 therapy. in accordance with the package insert and have been receiving the anti-PD-(L)1 therapy for \>3 months (with therapy currently ongoing) and have stable disease (as defined above), or had an initial period of stable disease or response and now have an initial scan demonstrating progressive disease per RECIST 1.1; or
2. Have confirmed progressive disease and discontinued prior anti-PD-(L)1 therapy and are now eligible for de novo NP-G2-044 plus standard of care anti-PD-1 therapy.
4. For Combination Therapy Expansion Cohort B, patients must have cutaneous squamous cell carcinoma (CSCC) (human papilloma virus \[HPV\]-positive or -negative; documentation of HPV status is required);
5. For Combination Therapy Expansion Cohort C, patients must have either:
1. Esophageal squamous cell carcinoma (ESCC) (HPV-positive or -negative; documentation of HPV status is required); or
2. Oropharyngeal squamous cell carcinoma (OPSCC) (HPV-positive or -negative; documentation of HPV status is required).
6. For Combination Therapy Expansion Cohort D, patients must have non muscle invasive bladder cancer (NMIBC) meeting Bacillus Calmette-Guérin (BCG)-unresponsive criteria;
7. For Combination Therapy Expansion Cohort E, patients must have microsatellite instability high (MSI-H) cancer;
8. For Combination Therapy Expansion Cohort F, patients must be immunotherapy naïve (I O naïve), have pancreatic ductal adenocarcinoma (PDAC), and meet the following criteria:
1. Have had stable disease or response with at least 4 months of standard of care chemotherapy;
2. Have no liver metastasis; and
3. Have albumin within the normal range at Screening and \>3.5 g/dL (±10%) 3 days before Cycle 1 Day 1.
9. For Combination Therapy Expansion Cohort G, patients must be I O naïve, have platinum resistant ovarian cancer (PROC), and meet the following criteria:
1. Had disease recurrence during or within 6 months after last administration of platinum-based chemotherapy; and
2. Received no more than 2 prior regimens of systemic therapy after development of platinum resistance.

1. Received chemotherapy or radiotherapy within 4 weeks or 5 half-lives, whichever is shorter, of the first dose of NP-G2-044; Note: Prior immunotherapy is allowed for patients receiving NP-G2-044 monotherapy. For PDAC patients in Combination Therapy Expansion Cohort F: received systemic therapy within 2 weeks of the first dose of NP-G2-044.
2. Unresolved toxicities from previous anti-cancer therapy, defined as toxicities (other than NCI CTCAE v5.0 Grade ≤2 alopecia or neuropathy) not yet resolved to NCI CTCAE v5.0 Grade ≤1; Note: Patients who experienced a Grade ≥3 anti-PD-1-related AE per NCI CTCAE v5.0 are excluded unless recovered and approved by the Novita Medical Monitor or designee.
3. Receiving any other investigational agent(s) or have received an investigational agent within 4 weeks of the first dose of NP-G2-044; Note: Patients who have progressed on NP-G2-044 treatment prior to this study are not eligible
4. Known untreated brain metastases or treated brain metastases that have not been radiographically and clinically stable (i.e., not requiring steroids) ≥4 weeks prior to study enrollment;
5. QTc by Fridericia method \>470 msec or electrocardiogram (ECG) with evidence of clinically meaningful conduction abnormalities or active ischemia as determined by the Investigator;
6. Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, hypertension, unstable angina pectoris, cardiac arrhythmia, autoimmune or inflammatory diseases, or psychiatric illness/social situations that would limit compliance with study requirements;
7. Pregnant, lactating, or is planning to attempt to become pregnant or impregnate someone during the study or within 90 days after dosing of NP-G2-044;
8. Received prior allogenic hematopoietic stem cell transplantation or allogenic bone marrow transplantation;
9. Received prior solid organ transplantation;
10. Ongoing immunosuppressive therapy (≥10 mg/day of prednisone or its equivalent);
11. Requires the use of a strong inhibitor or inducer of cytochrome P450 (CYP)3A4, CYP1A2, or CYP2D6 during the study;
12. History of clinically meaningful gastrointestinal bleeding, intestinal obstruction, or gastrointestinal perforation within 6 months of study enrollment;
13. Excluded by the Sponsor due to medical history, physical examination findings, clinical laboratory results, prior medications, or other entrance criteria; or
14. For PDAC patients in Combination Therapy Expansion Cohort F only: have a documented rise in tumor markers within the last 4 months.

Contacts and Locations

Study Contact

Sarah Cantwell

CONTACT

+1 5135799911

S.Cantwell@Medpace.com

Principal Investigator

Jillian Zhang, Ph.D.

STUDY_DIRECTOR

Novita Pharmaceuticals, Inc.

Study Locations (Sites)

Honor Health Research Institute

Scottsdale, Arizona, 85258

United States

University of Arizona - Cancer Center

Tucson, Arizona, 85719

United States

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205

United States

City of Hope

Duarte, California, 91010

United States

City of Hope Irvine Lennar

Irvine, California, 92618

United States

Hoag Memorial Hospital Presbyterian - Gynecologic Oncology Associates

Newport Beach, California, 92663

United States

Nuvance Health

Norwalk, Connecticut, 06856

United States

University of Florida (UF) - Shands Cancer Center

Gainesville, Florida, 32610

United States

Indiana University (IU) Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202

United States

University of Kansas Cancer Center

Fairway, Kansas, 66205

United States

Henry Ford Health System

Detroit, Michigan, 48202

United States

Atlantic Health System - Morristown Medical Center

Morristown, New Jersey, 07962

United States

University of Cincinnati (UC) - Cancer Institute

Cincinnati, Ohio, 45219

United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106

United States

University of Pennsylvania

Philadelphia, Pennsylvania, 19104

United States

University of Texas Southwestern

Dallas, Texas, 75390

United States

Virginia Cancer Specialists

Fairfax, Virginia, 22031

United States

Virginia Commonwealth University - Massey Cancer Center

Richmond, Virginia, 23298

United States

Collaborators and Investigators

Sponsor: Novita Pharmaceuticals, Inc.

Jillian Zhang, Ph.D., STUDY_DIRECTOR, Novita Pharmaceuticals, 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 Date2021-12-07

Study Completion Date2025-09

Study Record Updates

Study Start Date2021-12-07

Study Completion Date2025-09

Terms related to this study

Keywords Provided by Researchers

Advanced or Metastatic Solid Tumor Malignancies

Additional Relevant MeSH Terms

Advanced or Metastatic Solid Tumor Malignancies