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Solid Tumor, AdultPhase 1NCT04053673

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

A Phase 1 study testing RBN-2397 in people with Solid Tumor, Adult, run by Ribon Therapeutics, Inc. at 15 sites in 2 countries.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Tumor, Adult
What is being tested?
RBN-2397
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
130 participants
Where
15 sitesin 2 countries
Study dates
1 Aug 2019to 31 Jul 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.

Trial locations and contacts

15 sites in 2 countries.

Clinical Operations Manager contact

617-475-7203

clinicaltrials@ribontx.com

15 sites in 2 countries

United States11 sites, 11 recruiting

  • University of Colorado Anschutz Medical Campus

    Aurora, Colorado, 80045

    Aaron Parsons, 720-848-4603, aaron.parsons@cuanschutz.edu

    Erin Schenk, MD

    Recruiting

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

    Alicia Bilsky, 617-643-5965, abilsky@mgh.harvard.edu

    Dejan Juric, MD

    Recruiting

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

    James McCoy, 617-632-5485, James_McCoy@DFCI.HARVARD.EDU

    Geoffrey Shapiro, MD

    Recruiting

  • SCRI-Denver/HealthOne

    Denver, Colorado, 80218

    Gerald Falchook, MD, 281-221-0693, Gerald.Falchook@SarahCannon.com

    Gerald Falchook, MD

    Recruiting

  • MD Anderson Cancer Center

    Houston, Texas, 77030-4009

    Timothy A Yap, MD, PhD, 713-563-1784, tyap@mdanderson.org

    Timothy A Yap, MD, PhD

    Recruiting

  • SCRI-Nashville/Tennessee Oncology

    Nashville, Tennessee, 37203

    Melissa Johnson, MD, 615-329-7274, mjohnson@tnonc.com

    Melissa L. Johnson, MD

    Recruiting

  • Yale Cancer Center, Yale University

    New Haven, Connecticut, 06520

    Kwasi Boateng, 203-785-6993, kwasi.boateng@yale.edu

    Barbara Burtness, MD

    Recruiting

  • Sarah Cannon Research Institute at Florida Cancer Specialists

    Orlando, Florida, 32827

    Cesar Augusto Perez Batista, MD, 689-216-8500, Cesar.PerezBatista@flcancer.com

    Cesar Augusto Perez Batista, MD

    Recruiting

  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15213

    Amy Rose, kennaj@UPMC.EDU

    Yana Najjar, MD

    Recruiting

  • SCRI-Sarasota/Florida Cancer Specialists

    Sarasota, Florida, 34232

    Manish Patel, MD, 941-377-9993, mpatel@flcancer.com

    Manish Patel, MD

    Recruiting

  • Washington University

    St Louis, Missouri, 63110

    Maximilian Stroyeck, 314-253-2027, stroyeck@wustl.edu

    Saima Waqar, MD

    Recruiting

Other trials in United States

Spain4 sites, 4 recruiting

  • Hospital Quironsalud Barcelona - NEXT Oncology

    Barcelona, 08023

    Abigail Huerta, MD, +34 932 381 661, ahuerta@nextoncology.eu

    Marina Coll, +34 932 381 661, mcoll@nextoncology.eu

    Recruiting

  • Vall d'Hebron

    Barcelona, 08035

    Elena Garralda, MD, +34 93 274 6085, egarralda@vhio.net

    Josep Tabernero, MD

    Recruiting

  • Hospital Quironsalud Madrid - NEXT Oncology

    Madrid, 28223

    Cristina Gonzalez de Pedro, +34 914 521 900, cpedro@nextoncology.eu

    Valentina Boni, MD

    Recruiting

  • Hospital Clinic Universitario Biomedical Research institute INCLIVA

    Valencia

    Cristina Jorda, cjorda@incliva.es

    Andres Cervantes, MD

    Recruiting

Other trials in Spain

About this study

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

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.

Read the 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.

Being tested
RBN-2397
Keywords
Phase 1, PARP7 inhibition, First in Human, Solid Tumors, Interferon

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RBN-2397Drug

    an oral PARP7 Inhibitor

Study groups in NCT04053673
Study groupRoleWhat they receive
RBN-2397ExperimentalDose Escalation: Multiple doses of RBN-2397 for oral administration Dose Expansion: Oral dose of RBN-2397 as determined during Dose Escalation
Receives: Drug: RBN-2397

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)

    Incidence of Dose limiting Toxicities (DLTs)

    Measured: through first treatment cycle (an average of 21 days)

Secondary outcomes (5)

  1. Safety and tolerability

    Grade and frequency of adverse events and serious adverse events

    Measured: through study completion (an average of one year)

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

    Area-under-the-curve (AUC inf)

    Measured: Through Study Day 22

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

    Cmax

    Measured: Through Study Day 22

  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

    Objective response rate (ORR)

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

  5. Antitumor activity that may be associated with RBN-2397 treatment

    Disease control rate (DCR)

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Aug 2019
  2. Study start1 Aug 2019
  3. Primary completion30 Jun 2023 (estimated)
  4. Study completion31 Jul 2023 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Model description
Dose Expansion
Masking
None (open label)
Enrolment
130 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04053673
Sponsor's protocol ID
RBN-2397-19-001
Status last verified
Jul 2022
First submitted
5 Aug 2019
Last updated
28 Mar 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 29443986

  • 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.

    PubMed 34375612

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing RBN-2397 in people with Solid Tumor, Adult, run by Ribon Therapeutics, Inc. at 15 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 28 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Clinical Operations Manager (617-475-7203, clinicaltrials@ribontx.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) (time frame: through first treatment cycle (an average of 21 days)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04053673, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Mar 2023.

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