A Study of RGX-104 in Patients With Advanced Lung & Endometrial Cancer

NCT02922764 | Completed Phase 1 DMC

• 1 other identifier: RGX-104-001
• Study Type: interventional
• Target: 146
• Locations: 1 country
• Sites: 21

Brief Summary

Study RGX-104-001 is a Phase 1, first-in-human, dose escalation and expansion study of RGX-104, an oral small molecule targeting the liver X receptor (LXR), as a single agent and in combination with nivolumab, ipilimumab, docetaxel, or pembrolizumab plus carboplatin/pemetrexed.

Conditions

Endometrial Cancer; Endometrial Cancer Recurrent; Lung Cancer Recurrent; Lung Cancer; Non-small Cell Lung Cancer Metastatic; Non-small Cell Carcinoma

Keywords

Solid malignancy; Solid tumor; Non-small cell lung cancer; NSCLC; LXR; ApoE; Small cell lung cancer; SCLC; Endometrial; Endometrial Cancer; Malignant Neoplasms

Outcome Measures

Primary Outcomes (4)

• Maximum tolerated dose (MTD), or the maximum tested dose at which multiple DLTs are not observed, of RGX-104 as a single agent, and separately, in combination with nivolumab, ipilimumab, docetaxel, or pembrolizumab plus carboplatin/pemetrexed.

  6 months

• Overall response rate associated with RGX-104 treatment as a single agent, and separately, in combination with docetaxel or pembrolizumab plus carboplatin/pemetrexed.

  24 months

• Progression-free survival associated with RGX-104 treatment as a single agent, and separately, in combination with docetaxel or pembrolizumab plus carboplatin/pemetrexed.

  24 months

• Number of participants with treatment-emergent adverse events associated with RGX-104 treatment as a single agent, and separately, in combination with nivolumab, ipilimumab, docetaxel, or pembrolizumab plus carboplatin/pemetrexed.

  24 months

Secondary Outcomes (2)

• Pharmacokinetics: Maximum Plasma Concentration (Cmax) of RGX-104.

  24 months

• Pharmacokinetics: Area Under the Curve (AUC) of RGX-104.

  24 months

Study Arms (4)

Recurrent NSCLC (2nd/3rd Line Lung Cancer). Expansion

EXPERIMENTAL

RGX-104 in combination docetaxel RGX104 120 mg BID (5day on/2days off)

Drug: RGX-104; Drug: Docetaxel

Newly dignosed NSCLC Cohort Expansion

EXPERIMENTAL

RGX104 + pembrolizumab + carboplatin/pemetrexed RGX104 120 mg BID (5day on/2days off)

Drug: RGX-104; Drug: Pembrolizumab; Drug: Carboplatin; Drug: Pemetrexed

Recurrent/Relapsed Small Cell Lung Cancer (SCLC) Expansion

EXPERIMENTAL

RGX-104 + docetaxel RGX104 120 mg BID (5day on/2days off)

Drug: Docetaxel

Recurrent/Relapsed Endometrial Cancer Expansion

EXPERIMENTAL

RGX-104 combined with ipilimumab RGX104 120 mg BID (5day on/2days off)

Drug: RGX-104; Drug: Ipilimumab

Interventions

RGX-104 DRUG

Newly dignosed NSCLC Cohort Expansion; Recurrent NSCLC (2nd/3rd Line Lung Cancer). Expansion; Recurrent/Relapsed Endometrial Cancer Expansion

Ipilimumab DRUG

Recurrent/Relapsed Endometrial Cancer Expansion

Docetaxel DRUG

Recurrent NSCLC (2nd/3rd Line Lung Cancer). Expansion; Recurrent/Relapsed Small Cell Lung Cancer (SCLC) Expansion

Pembrolizumab DRUG

Newly dignosed NSCLC Cohort Expansion

Carboplatin DRUG

Newly dignosed NSCLC Cohort Expansion

Pemetrexed DRUG

Newly dignosed NSCLC Cohort Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient must have histologic or cytologic evidence of a malignant solid tumor or lymphoma (any histology) and must have advanced disease, defined as cancer that is either metastatic or locally advanced and unresectable (and for which additional radiation therapy or other locoregional therapies are not considered feasible).
• With the exception of dose escalation with pembrolizumab plus carboplatin/pemetrexed, patients enrolled in the dose escalation stages must have disease that is resistant to or relapsed following available standard systemic therapy, or for which there is no standard systemic therapy or reasonable therapy in the physician's judgment likely to result in clinical benefit or if such therapy has been refused by the patient. Documentation of the reason must be provided for patients who have not received a standard therapy likely to result in clinical benefit.
• Patients enrolled in the expansion stages: Optional tumor biopsy may be obtained during the screening period and toward the beginning of Cycle 2 or at the time of PD, if earlier. If a biopsy is deemed by the investigator to not be in the patient's best interest, prior approval must be obtained from the Medical Monitor to waive this requirement.
• The patient must have disease that is measurable by standard imaging techniques per RECIST or immune-related response criteria (irRC; all tumor types except lymphoma) or International Working Group (IWG) revised response criteria for malignant lymphoma (lymphoma only). For patients with prior radiation therapy, measurable lesions must be outside of any prior radiation field(s), unless disease progression has been documented at that disease site subsequent to radiation.
• The patient is ≥18 years old.
• The patient has an ECOG PS of ≤1.
• The patient has adequate baseline organ function, as demonstrated by the following:
• Serum creatinine ≤1.5 × institutional upper limit of normal (ULN) or calculated creatinine clearance \>30 mL/min (\>45 ml/min for patients receiving carboplatin/pemetrexed).
• Serum albumin ≥2.5 g/dl;
• Bilirubin ≤1.5 × institutional ULN.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × institutional ULN. Patients enrolled in an expansion stage may have ALT and AST \< 5 × institutional ULN if the patient has hepatic metastases;
• For patients not taking warfarin or other oral anticoagulants: international normalized ratio (INR) ≤1.5 or prothrombin time (PT) ≤1.5 × ULN; and either partial thromboplastin time or activated partial thromboplastin time (PTT or aPTT) ≤1.5 × ULN. Patients taking warfarin should be on a stable dose that results in a stable INR \<3.5. Among patients receiving other oral anticoagulant therapy, PT or aPTT must be within the intended therapeutic range of the anticoagulant.
• The patient has adequate baseline hematologic function, as demonstrated by the following:
• Absolute neutrophil count (ANC) ≥1.5×109/L;
• Hemoglobin ≥8 g/dL and no red blood cell (RBC) transfusions during the prior 14 days;

You may not qualify if:

• If considered for combination therapy with nivolumab or ipilimumab, the patient has:
• Uncontrolled clinically significant pulmonary disease.
• A history of any grade immune-related ocular event.
• A history of Grade ≥3 immune-related adverse event regardless of offending agent.
• Active autoimmune disease that required systemic treatment in the past. Patients who have not required systemic treatment for at least two years may be enrolled if permission is provided after discussion with the Medical Monitor (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).
• Evidence of active noninfectious pneumonitis or history of interstitial lung disease.
• A risk of reactivation of hepatitis B or C.
• Previously received an immune therapy that was discontinued due to immune-related AEs, regardless of grade.
• Uncontrolled endocrine disorder. Patients who are on endocrine replacement therapy must be on a stable dose.
• The patient has received treatment with chemotherapy, external-beam radiation, or other systemic anticancer therapy within 14 days prior to study therapy administration (42 days for prior nitrosourea or mitomycin-C; patients with advanced prostate cancer who are receiving luteinizing hormone releasing hormone (LHRH) agonists are permitted onto the study and should continue use of these agents during study treatment).
• The patient has received treatment with an investigational systemic anticancer agent within 14 days prior to study therapy administration.
• The patient has previously received treatment with RGX-104 or another investigational agent that is a known LXR agonist.
• The patient has an additional active malignancy that may confound the assessment of the study endpoints. Patients with a past cancer history with substantial potential for recurrence must be discussed with the Medical Monitor before study entry. Patients with the following concomitant neoplastic diagnoses are eligible: non-melanoma skin cancer, carcinoma in situ (including transitional cell carcinoma, cervical intraepithelial neoplasia, and melanoma in situ), organ-confined prostate cancer with no evidence of progressive disease.
• The patient has clinically significant cardiovascular disease (e.g., uncontrolled or any New York Heart Association Class 3 or 4 heart failure (see Appendix 1), uncontrolled angina, history of myocardial infarction, unstable angina or stroke within 6 months prior to study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication).
• The patient has uncontrolled, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease, pulmonary hypertension) that in the opinion of the Investigator would put the patient at significant risk for pulmonary complications during the study.

Sponsors & Collaborators

• Inspirna, Inc.: lead

Study Sites (21)

Arizona Oncology

Tucson, Arizona, 85711, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Rocky Mountain Cancer Centers

Denver, Colorado, 80218, United States

Location

Sarah Cannon Research Institute

Denver, Colorado, 80218, United States

Location

Florida Cancer Specialist

Lake Mary, Florida, 32799, United States

Location

Comprehensive Hematology Oncology

St. Petersburg, Florida, 33709, United States

Location

James Graham Brown Cancer Center

Louisville, Kentucky, 40202, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

Maryland Oncology

Columbia, Maryland, 21044, United States

Location

Regions Hospital

Saint Paul, Minnesota, 55101, United States

Location

Dartmouth Hitchcock Medical

Lebanon, New Hampshire, 03756, United States

Location

CINJ

New Brunswick, New Jersey, 08901, United States

Location

Quantum Santa Fe

Santa Fe, New Mexico, 87505, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

OU Health Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Oregon Health Sciences University

Portland, Oregon, 97239, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

The Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

MeSH Terms

Conditions

Endometrial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Small Cell Lung Carcinoma; Neoplasms

Interventions

Ipilimumab; Docetaxel; pembrolizumab; Carboplatin; Pemetrexed

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic

Study Officials

• Robert Wasserman, MD

  Inspirna, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2016
• First Posted: October 4, 2016
• Study Start: November 1, 2016
• Primary Completion: January 22, 2025
• Study Completion: January 22, 2025
• Last Updated: March 26, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (21)