Description:
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.
Title
- Brief Title: RBN-2397, an Oral PARP7 Inhibitor, in Patients With Solid Tumors , FIH, MAD 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
Clinical Trial IDs
- ORG STUDY ID:
RBN-2397-19-001
- NCT ID:
NCT04053673
Conditions
Interventions
Drug | Synonyms | Arms |
---|
RBN-2397 | | RBN-2397 |
Purpose
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
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.
After the MTD is determined, Expansion Cohort(s) of approximately 20 participants each will
be enrolled to further examine the safety, PK, pharmacodynamics, and antitumor activity of
RBN-2397 at the MTD or other dose recommended for further investigation. Based on nonclinical
data as well as clinical data obtained from the dose-escalation portion of this study,
enrollment in the Expansion Cohort(s) may be limited to specific tumor type(s), as warranted
by the data.
Trial Arms
Name | Type | Description | Interventions |
---|
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 | |
Eligibility Criteria
Inclusion Criteria:
- 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.
- Male or female aged ≥18 years.
- 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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) |
Time Frame: | through study completion (an average of one year) |
Safety Issue: | |
Description: | Frequency of Dose limiting Toxicities (DLTs) |
Secondary Outcome Measures
Measure: | Area under the plasma concentration |
Time Frame: | Through Study Day 22 |
Safety Issue: | |
Description: | Area-under-the-curve (AUC inf) |
Measure: | Peak plasma concentration |
Time Frame: | Through Study Day 22 |
Safety Issue: | |
Description: | Cmax |
Measure: | 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) |
Safety Issue: | |
Description: | Objective response rate (ORR) |
Measure: | Antitumor activity that may be associated with RBN-2397 treatment |
Time Frame: | Every 6-8 weeks; through study completion (an average of one year) |
Safety Issue: | |
Description: | Disease control rate (DCR) |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Ribon Therapeutics, Inc. |
Trial Keywords
- Phase 1
- PARP7 inhibition
- First in Human
- Solid Tumors
- Interferon
Last Updated
August 26, 2021