Phase 1 Study of RBN-2397, an Oral PARP7 Inhibitor, in Patients With Solid Tumors

NCT04053673 | Unknown Phase 1 FDA Drug

• 1 other identifier: RBN-2397-19-001
• Study Type: interventional
• Target: 130
• Locations: 2 countries
• Sites: 15

Brief Summary

RBN-2397 inhibits PARP7, an enzyme that is switched on by cancer stresses, such as the toxins in cigarette smoke. Cancer cells use PARP7 to hide from the immune system by stopping the cell from sending a signal (Type 1 interferon) that tells the immune system that something is wrong and to kill the cell. RBN-2397 has been shown in animal studies to inhibit tumor growth and also shuts down the "don't kill me" signal the tumor is sending to evade the immune system. As a PARP7 inhibitor RBN-2397 is different from drugs inhibiting PARP1, PARP2 and PARP3 enzymes which are approved for the treatment of certain ovarian and breast cancers. The primary purpose of this study is to determine the maximum tolerated dose (MTD) of orally administered RBN-2397 in patients with advanced or metastatic solid tumors. This study will also evaluate the safety and tolerability of RBN-2397, examine the pharmacokinetics (PK) (measure how the body absorbs, breaks down and eliminates RBN-2397) and investigate whether it has antitumor activity in solid tumor cancers.

Conditions

Solid Tumor, Adult

Keywords

Phase 1; PARP7 inhibition; First in Human; Solid Tumors; Interferon

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)

  Incidence of Dose limiting Toxicities (DLTs)

  through first treatment cycle (an average of 21 days)

Secondary Outcomes (5)

• Safety and tolerability

  through study completion (an average of one year)

• Area under the plasma concentration for tablet manufactured with micronized RBN-2397 relative to unmicronized RBN-2397 (standard tablet) (Relative Bioavailability Cohorts only)

  Through Study Day 22

• Peak plasma concentration for tablet manufactured with micronized RBN-2397 relative to unmicronized RBN-2397 (standard tablet) (Relative Bioavailability Cohorts only)

  Through Study Day 22

• Antitumor activity that may be associated with RBN-2397 treatment assessed by CT/MRI Response Evaluation Criteria for Solid Tumors (RECIST) Criteria v1.1

  Every 6-8 weeks; through study completion (an average of one year)

• Antitumor activity that may be associated with RBN-2397 treatment

  Every 6-8 weeks; through study completion (an average of one year)

Study Arms (1)

RBN-2397

EXPERIMENTAL

Dose Escalation: Multiple doses of RBN-2397 for oral administration Dose Expansion: Oral dose of RBN-2397 as determined during Dose Escalation

Drug: RBN-2397

Interventions

RBN-2397 DRUG

an oral PARP7 Inhibitor

RBN-2397

Eligibility Criteria

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

You may qualify if:

• Dose Escalation Phase only: Metastatic or advanced-stage solid malignant tumor (which may include "solid" lymphoma \[e.g., mantle cell\]) for whom no therapy exists that would be curative or might provide clinical benefit.
• Dose Expansion Phase Only: Patients with locally advanced or metastatic solid tumors, with at least one measurable lesion as determined by RECIST version 1.1, who have received standard therapy or are intolerant of standard therapy, have progressed following their last prior therapy, and have one of the following tumor types:
• SCCL: Histologically confirmed NSCLC of predominantly squamous cell histology and must have received no more than 3 lines of prior systemic therapy including chemotherapy regimens and/or immune checkpoint inhibitor therapy (combination allowed).
• HNSCC: Histologically confirmed squamous cell carcinoma of the head and neck (either HPV-positive or -negative) and must have received no more than 3 lines of prior systemic immunotherapy and/or chemotherapeutic treatments in the metastatic setting. Includes primary tumor location of the oral cavity, oropharynx, hypopharynx, larynx, and paranasal sinuses (nasopharyngeal carcinoma, skin squamous cell carcinoma, and salivary gland carcinomas are not eligible).
• HR+ breast cancer: Histologically confirmed diagnosis of estrogen receptor (ER) and/or progesterone receptor (PR) positive, HER2-negative adenocarcinoma of breast (as per local laboratory testing) whose disease has failed standard systemic therapy for locally advanced or metastatic disease and must have received no more than 1 prior chemotherapeutic for advanced/metastatic disease.
• PARP7 amplified: Tumor with documented PARP7 (or TIPARP) gene copy amplification as determined by a CLIA certified laboratory test (e.g., FoundationOne CDx) that has failed standard systemic therapy for locally advanced or metastatic disease.
• Must agree to undergo tumor biopsy Normal organ and bone marrow function Patient and his/her partner agree to use adequate contraception during and for 3 months after the last study drug dose

You may not qualify if:

• Unable to swallow oral medications
• Major surgery within 4 weeks of starting study
• Pregnant or breast-feeding.
• Receiving intravenous antibiotics for an active infection
• Known human immunodeficiency virus (HIV) or hepatitis B or C infection.
• History of a different malignancy unless disease-free for at least 5 years
• Some medications are not allowed while on study. Interested participants will need to inform study doctor of all the medications he/she is taking.
• Herbal medicines, and grapefruit, grapefruit juice, pomegranate juice, star fruit or orange marmalade (made with Seville oranges) are not allowed to be taken during study.

Sponsors & Collaborators

• Ribon Therapeutics, Inc.: lead

Study Sites (15)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

RECRUITING

SCRI-Denver/HealthOne

Denver, Colorado, 80218, United States

RECRUITING

Yale Cancer Center, Yale University

New Haven, Connecticut, 06520, United States

RECRUITING

Sarah Cannon Research Institute at Florida Cancer Specialists

Orlando, Florida, 32827, United States

RECRUITING

SCRI-Sarasota/Florida Cancer Specialists

Sarasota, Florida, 34232, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Washington University

St Louis, Missouri, 63110, United States

RECRUITING

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

SCRI-Nashville/Tennessee Oncology

Nashville, Tennessee, 37203, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030-4009, United States

RECRUITING

Hospital Quironsalud Barcelona - NEXT Oncology

Barcelona, 08023, Spain

RECRUITING

Vall d'Hebron

Barcelona, 08035, Spain

RECRUITING

Hospital Quironsalud Madrid - NEXT Oncology

Madrid, 28223, Spain

RECRUITING

Hospital Clinic Universitario Biomedical Research institute INCLIVA

Valencia, Spain

RECRUITING

Related Publications (2)

• Cohen MS, Chang P. Insights into the biogenesis, function, and regulation of ADP-ribosylation. Nat Chem Biol. 2018 Feb 14;14(3):236-243. doi: 10.1038/nchembio.2568.

  PMID: 29443986 BACKGROUND

• Gozgit JM, Vasbinder MM, Abo RP, Kunii K, Kuplast-Barr KG, Gui B, Lu AZ, Molina JR, Minissale E, Swinger KK, Wigle TJ, Blackwell DJ, Majer CR, Ren Y, Niepel M, Varsamis ZA, Nayak SP, Bamberg E, Mo JR, Church WD, Mady ASA, Song J, Utley L, Rao PE, Mitchison TJ, Kuntz KW, Richon VM, Keilhack H. PARP7 negatively regulates the type I interferon response in cancer cells and its inhibition triggers antitumor immunity. Cancer Cell. 2021 Sep 13;39(9):1214-1226.e10. doi: 10.1016/j.ccell.2021.06.018. Epub 2021 Jul 22.

  PMID: 34375612 BACKGROUND

Study Officials

• Melissa L Johnson, MD

  Tennessee Oncology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Operations Manager

CONTACT

617-475-7203; clinicaltrials@ribontx.com

Study Design

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

Model Details: Dose Expansion

Study Record Dates

• First Submitted: August 5, 2019
• First Posted: August 12, 2019
• Study Start: August 1, 2019
• Primary Completion: June 30, 2023
• Study Completion: July 31, 2023
• Last Updated: March 28, 2023

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

ES (4); US (11)