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

NCT ID: NCT04053673

Last Updated: 2023-03-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1

Total Enrollment

130 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-08-01

Study Completion Date

2023-07-31

Brief Summary

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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.

Detailed Description

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This is a first-in-human, Phase 1, multi-center, open-label, dose-escalation study to:

* Evaluate the safety profile and MTD of RBN-2397 administered orally and establish the RBN-2397 dose(s) and schedule(s) recommended for further investigation in Phase 2
* Characterize the PK profile of RBN-2397
* Identify preliminary antitumor activity.
* Biomarkers and their correlation with response to RBN-2397 and other outcomes will be examined.

Cohorts will follow a traditional 3 + 3 design. After enrollment of the first participant within a cohort, there must be a wait period of at least 1 week before enrollment of additional participants in that cohort. This dose escalation phase of the study is complete.

The study is currently in the Relative Bioavailability and Expansion Cohort(s) phase where approximately 20 participants each will be enrolled to further examine the safety, PK, pharmacodynamics, and antitumor activity of RBN-2397 at the recommended phase 2 dose.

Relative Bioavailability Assessment:

An evaluation of relative bioavailability of a micronized RBN-2397 tablet versus the standard RBN-2397 tablet (manufactured with unmicronized RBN-2397 and used in the dose escalation phase of the study) will be performed as part of the dose escalation phase. Micronized tablets will be used in the Dose Expansion Phase of the study after the relative bioavailability assessment has been completed.

Dose Expansion Phase The recommended phase 2 dose will be investigated in the following cancer types: squamous cell carcinoma of the lung (SCCL), head and neck squamous cell carcinoma (HNSCC), hormone receptor positive (HR+) breast cancer, and PARP7 amplified cancer.

Duration of treatment:

It is anticipated that the minimum study involvement will be one cycle. Participants are eligible to have an indefinite number of additional cycles of treatment if their disease does not progress and they do not have unacceptable side effects.

Conditions

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Solid Tumor, Adult

Study Design

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Allocation Method

NA

Intervention Model

SEQUENTIAL

Dose Expansion
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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RBN-2397

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

Group Type EXPERIMENTAL

RBN-2397

Intervention Type DRUG

an oral PARP7 Inhibitor

Interventions

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RBN-2397

an oral PARP7 Inhibitor

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ribon Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Melissa L Johnson, MD

Role: PRINCIPAL_INVESTIGATOR

Tennessee Oncology

Locations

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University of Colorado Anschutz Medical Campus

Aurora, Colorado, United States

Site Status RECRUITING

SCRI-Denver/HealthOne

Denver, Colorado, United States

Site Status RECRUITING

Yale Cancer Center, Yale University

New Haven, Connecticut, United States

Site Status RECRUITING

Sarah Cannon Research Institute at Florida Cancer Specialists

Orlando, Florida, United States

Site Status RECRUITING

SCRI-Sarasota/Florida Cancer Specialists

Sarasota, Florida, United States

Site Status RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status RECRUITING

Washington University

St Louis, Missouri, United States

Site Status RECRUITING

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

SCRI-Nashville/Tennessee Oncology

Nashville, Tennessee, United States

Site Status RECRUITING

MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

Hospital Quironsalud Barcelona - NEXT Oncology

Barcelona, , Spain

Site Status RECRUITING

Vall d'Hebron

Barcelona, , Spain

Site Status RECRUITING

Hospital Quironsalud Madrid - NEXT Oncology

Madrid, , Spain

Site Status RECRUITING

Hospital Clinic Universitario Biomedical Research institute INCLIVA

Valencia, , Spain

Site Status RECRUITING

Countries

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United States Spain

Central Contacts

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Clinical Operations Manager

Role: CONTACT

617-475-7203

Facility Contacts

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Aaron Parsons

Role: primary

720-848-4603

Gerald Falchook, MD

Role: primary

281-221-0693

Kwasi Boateng

Role: primary

203-785-6993

Cesar Augusto Perez Batista, MD

Role: primary

689-216-8500

Manish Patel, MD

Role: primary

941-377-9993

Alicia Bilsky

Role: primary

617-643-5965

James McCoy

Role: primary

617-632-5485

Maximilian Stroyeck

Role: primary

314-253-2027

Amy Rose

Role: primary

Melissa Johnson, MD

Role: primary

615-329-7274

Timothy A Yap, MD, PhD

Role: primary

713-563-1784

Abigail Huerta, MD

Role: primary

+34 932 381 661

Marina Coll

Role: backup

+34 932 381 661

Elena Garralda, MD

Role: primary

+34 93 274 6085

Cristina Gonzalez de Pedro

Role: primary

+34 914 521 900

Cristina Jorda

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 29443986 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 34375612 (View on PubMed)

Other Identifiers

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RBN-2397-19-001

Identifier Type: -

Identifier Source: org_study_id

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