Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04053673
Recruitment Status : Recruiting
First Posted : August 12, 2019
Last Update Posted : November 24, 2021
Sponsor:
Information provided by (Responsible Party):
Ribon Therapeutics, Inc.

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.


Condition or disease Intervention/treatment Phase
Solid Tumor, Adult Drug: RBN-2397 Phase 1

Detailed Description:

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description: Dose Expansion
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, First-in-human Study of the Safety, Single- and Multiple-Dose Pharmacokinetics, and Preliminary Activity of Escalating Doses of RBN-2397, an Oral PARP7 Inhibitor, in Patients With Solid Tumors
Actual Study Start Date : August 1, 2019
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : January 31, 2023

Arm Intervention/treatment
Experimental: RBN-2397
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
an oral PARP7 Inhibitor




Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) [ Time Frame: through first treatment cycle (an average of 21 days) ]
    Incidence of Dose limiting Toxicities (DLTs)


Secondary Outcome Measures :
  1. Safety and tolerability [ Time Frame: through study completion (an average of one year) ]
    Grade and frequency of adverse events and serious adverse events

  2. Area under the plasma concentration for tablet manufactured with micronized RBN-2397 relative to unmicronized RBN-2397 (standard tablet) (Relative Bioavailability Cohorts only) [ Time Frame: Through Study Day 22 ]
    Area-under-the-curve (AUC inf)

  3. Peak plasma concentration for tablet manufactured with micronized RBN-2397 relative to unmicronized RBN-2397 (standard tablet) (Relative Bioavailability Cohorts only) [ Time Frame: Through Study Day 22 ]
    Cmax

  4. Antitumor activity that may be associated with RBN-2397 treatment assessed by CT/MRI Response Evaluation Criteria for Solid Tumors (RECIST) Criteria v1.1 [ Time Frame: Every 6-8 weeks; through study completion (an average of one year) ]
    Objective response rate (ORR)

  5. Antitumor activity that may be associated with RBN-2397 treatment [ Time Frame: Every 6-8 weeks; through study completion (an average of one year) ]
    Disease control rate (DCR)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04053673


Contacts
Layout table for location contacts
Contact: Clinical Operations Manager 617-475-7203 clinicaltrials@ribontx.com

Locations
Layout table for location information
United States, Colorado
University of Colorado Anschutz Medical Campus Recruiting
Aurora, Colorado, United States, 80045
Contact: Aaron Parsons    720-848-4603    aaron.parsons@cuanschutz.edu   
Principal Investigator: Erin Schenk, MD         
SCRI-Denver/HealthOne Recruiting
Denver, Colorado, United States, 80218
Contact: Gerald Falchook, MD    281-221-0693    Gerald.Falchook@SarahCannon.com   
Principal Investigator: Gerald Falchook, MD         
United States, Connecticut
Yale Cancer Center, Yale University Recruiting
New Haven, Connecticut, United States, 06520
Contact: Haley Dunning    203-785-4267    Haley.dunning@yale.edu   
Principal Investigator: Patricia LoRusso, DO, PhD         
United States, Florida
SCRI-Sarasota/Florida Cancer Specialists Recruiting
Sarasota, Florida, United States, 34232
Contact: Manish Patel, MD    941-377-9993    mpatel@flcancer.com   
Principal Investigator: Manish Patel, MD         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Shannon Smith    617-643-5965    ssmith164@mgh.harvard.edu   
Principal Investigator: Dejan Juric, MD         
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Amanda Fiorentino    617-632-5485    amandam_fiorentino@dcfi.harvard.edu   
Principal Investigator: Geoffrey Shapiro, MD         
United States, Tennessee
SCRI-Nashville/Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37203
Contact: Melissa Johnson, MD    615-329-7274    mjohnson@tnonc.com   
Principal Investigator: Melissa L. Johnson, MD         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030-4009
Contact: Timothy A Yap, MD, PhD    713-563-1784    tyap@mdanderson.org   
Principal Investigator: Timothy A Yap, MD, PhD         
Sponsors and Collaborators
Ribon Therapeutics, Inc.
Investigators
Layout table for investigator information
Principal Investigator: Melissa L Johnson, MD Tennessee Oncology, PLLC
Publications:
Layout table for additonal information
Responsible Party: Ribon Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT04053673    
Other Study ID Numbers: RBN-2397-19-001
First Posted: August 12, 2019    Key Record Dates
Last Update Posted: November 24, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ribon Therapeutics, Inc.:
Phase 1
PARP7 inhibition
First in Human
Solid Tumors
Interferon
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms