RBN-2397, an Oral PARP7 Inhibitor, in Patients With Solid Tumors , FIH, MAD Study
|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 : August 12, 2019
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|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||120 participants|
|Intervention Model:||Sequential Assignment|
|Intervention Model Description:||Dose Escalation|
|Masking:||None (Open Label)|
|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, 2020|
|Estimated Study Completion Date :||January 31, 2021|
Dose Escalation: Multiple doses of RBN-2397 for oral administration Dose Expansion: Oral dose of RBN-2397 as determined during Dose Escalation
an oral PARP7 Inhibitor
- Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) [ Time Frame: through study completion (an average of one year) ]Frequency of Dose limiting Toxicities (DLTs)
- Safety and tolerability [ Time Frame: through study completion (an average of one year) ]Grade and frequency of adverse events and serious adverse events
- Area under the plasma concentration [ Time Frame: Through Study Day 22 ]Area-under-the-curve (AUC inf)
- Peak plasma concentration [ Time Frame: Through Study Day 22 ]Cmax
- 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)
- 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)
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
|Contact: Sudha Parasuraman, MDfirstname.lastname@example.org|
|Contact: Kristy Kuplast-Barr, BS||617 914 email@example.com|
|United States, Colorado|
|Denver, Colorado, United States, 80218|
|Contact: Gerald Falchook, MD 281-221-0693 Gerald.Falchook@SarahCannon.com|
|Principal Investigator: Gerald Falchook, MD|
|United States, Florida|
|SCRI-Sarasota/Florida Cancer Specialists||Recruiting|
|Sarasota, Florida, United States, 34232|
|Contact: Manish Patel, MD 941-377-9993 firstname.lastname@example.org|
|Principal Investigator: Manish Patel, MD|
|United States, Tennessee|
|Nashville, Tennessee, United States, 37203|
|Contact: Melissa Johnson, MD 615-329-7274 email@example.com|
|Principal Investigator: Melissa L. Johnson, MD|
|Principal Investigator:||Melissa L Johnson, MD||Tennessee Oncology, PLLC|