Trial Title:
RBN-2397 in Combination With Pembrolizumab in Patients With SCCL
NCT ID:
NCT05127590
Condition:
Advanced Squamous Non-Small Cell Lung Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Non-Small-Cell Lung
Pembrolizumab
Conditions: Keywords:
NSCLC
Squamous Cell Lung Cancer
Squamous - NSCLC
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Active, not recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
RBN-2397 in combination with pembrolizumab
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
RBN-2397
Description:
Continuous oral dosing with the RP2D of RBN-2397 (outpatient basis). Pembrolizumab IV
infusion over 30 minutes in clinic on Day 1 of each cycle.
Arm group label:
RBN-2397 in combination with pembrolizumab
Other name:
Pembrolizumab
Other name:
Keytruda
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 and human
studies to inhibit tumor growth and also shuts down the "don't kill me" signal the tumor
is sending to evade the immune system.
The purpose of this study is to determine if RBN-2397 in combination with pembrolizumab
(a PD-1 inhibitor) has the ability to restore the response to treatment in patients with
SCCL that have been previously treated with a PD-1/PD-1 ligand (PD-L1) inhibitor and have
had a response followed by disease progression.
The Phase 1b portion of the study will assess the safety of RBN-2397 in combination with
pembrolizumab (a PD-1 inhibitor) and define the dose of RBN-2397 to be used in
combination with pembrolizumab for the Phase 2.
The Phase 2 portion of the study will assess the anti-tumor activity of RBN-2397 in
combination with pembrolizumab.
Detailed description:
This is an open label, multicenter Phase 1b/2 single arm study that will evaluate the
safety and antitumor activity of RBN-2397 in combination with pembrolizumab in patients
with confirmed diagnosis of advanced squamous cell carcinoma of the lung who have
received prior therapy. The study consists of a Phase 1b Safety Run in and Phase 2.
During the Phase 1b Safety Run-in, approximately 10 patients will be enrolled in a 3+3
fashion and treated with continuous oral dosing with RBN-2397 twice daily (BID) in
combination with the fixed approved dose of intravenous (IV) pembrolizumab every 3 weeks
[Q3W]) to establish RP2D of RBN-2397 in combination with pembrolizumab.
During Phase 2, approximately 40 patients will be treated with continuous oral dosing
with the RP2D of RBN-2397 BID in combination with the fixed approved dose of IV
pembrolizumab.
In both the Phase 1b Safety Run in and Phase 2, a treatment cycle is defined as 21 days.
On Day 1 of each treatment cycle, RBN-2397 will be administered orally and followed by IV
infusion of pembrolizumab at the fixed approved dose according to the approved local
product label. During the remaining days of the 21-day treatment cycle, only RBN-2397 BID
will be administered. Treatment cycles will continue until disease progression,
unacceptable treatment-related toxicity, or withdrawal of consent
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Confirmed diagnosis of advanced/metastatic NSCLC of squamous cell histology as
determined by local testing practices.
2. Patients should have received prior therapy including a platinum containing
chemotherapy regimen and an ICI, including anti-PD-1/anti-PD-L1, anti-cytotoxic
T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors, either sequentially or as
combination of chemo + checkpoint inhibitor.
3. The last regimen prior to enrolling in the study must be a checkpoint
inhibitor-containing regimen where the best response for at least one tumor response
assessment was stable disease (SD), partial response (PR), or complete response
(CR).
4. Patients experienced PD as determined by the investigator during or following their
most recent treatment regimen
5. Must agree to undergo tumor biopsy if medically safe and feasible. Archival biopsy
samples may be submitted if fresh biopsy can't be obtained.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
7. CT or MRI imaging done within 28 days prior to study treatment and have at least one
measurable target lesion
8. Normal organ and bone marrow function
9. Patient and his/her partner agree to use adequate contraception during and for 3
months after the last study drug dose
Exclusion Criteria:
1. Has non-squamous histology NSCLC. Patients whose tumors have a mixed histology are
ineligible.
2. Patient should not have received more than two prior lines of therapy with ICI
including anti-PD-1/anti-PD-L1, anti-CTLA-4 inhibitors and one prior line of a
chemotherapy treatment.
3. Patient is unable to swallow oral medications, has impairment of gastrointestinal
(GI) function or GI disease that may significantly alter drug absorption (e.g.,
active inflammatory bowel disease, uncontrolled nausea, vomiting, diarrhea, or
malabsorption syndrome).
4. Prior radiation within 2 weeks of Cycle 1 Day 1 (C1D1), except for palliative
radiotherapy to a limited field. Patients must have recovered from all radiation
related toxicities, not require corticosteroids, and not have had radiation
pneumonitis. A 1-week washout is permitted for palliative radiation (≤ 2 weeks of
radiotherapy) to non CNS disease.
5. A patient with CNS metastases is excluded if:
- Has active CNS metastases (new lesions or progression from prior imaging study)
requiring treatment within 28 days prior to study treatment and/or ongoing
corticosteroid therapy.
- Has symptomatic or untreated leptomeningeal disease.
6. Patients who discontinue prior treatment with an ICI due to irAEs.
7. Has a known history of prior malignancy within the last 5 years. Except:
malignancies that were treated curatively and have not recurred within 2 years prior
to study treatment; completely resected basal cell and squamous cell skin cancers;
any malignancy considered to be indolent and that has never required therapy; and
completely resected carcinoma in situ of any type.
8. Has received a live-virus vaccination within 30 days of planned treatment start.
Vaccines that do not contain live virus are permitted.
9. Any of the following in the previous 6 months: myocardial infarction or current
history of New York heart Association (NYHA) Class III or IV heart failure,
uncontrolled angina, severe uncontrolled ventricular anemias, or
electrocardiographic evidence of acute ischemia.
10. Patient has a history of prolonged QT syndrome or Torsades de pointes, and/or has a
familial history of prolonged QT syndrome.
11. Patient is taking a concomitant medication that is a strong inhibitor or inducer of
cytochrome P450 [CYP]-mediated metabolism or that is metabolized by CYP 2B6, 3A4 or
2C19, 2C9, or other members of the IIC subfamily of the CYP genes and that, if
underdosed, would constitute a significant risk to the patient. Individual cases may
be discussed with the Medical Monitor.
12. Ingestion of herbal medicines and grapefruit, grapefruit juice, pomegranate juice,
star fruit, or orange marmalade (made with Seville oranges) from the start of the
screening period. (Note that there are well- reported cases of CYP3A drug-drug
interactions with these foodstuffs.)
13. Has active autoimmune disease that has required systemic treatment in the past 12
months (i.e., with use of disease modifying agents, corticosteroids or
immunosuppressive drugs). Replacement therapy (e.g., ≤ 10 mg daily prednisolone or
steroid equivalent, thyroxine, insulin, or corticosteroid replacement therapy for
adrenal or pituitary insufficiency, etc.) is not considered a form of systemic
treatment. Patients with vitiligo, resolved childhood asthma/atopy, type I diabetes
mellitus, and residual hypothyroidism due to an autoimmune condition and only
requiring hormone replacement, are not excluded.
14. Is on chronic systemic steroids (e.g., > 10 mg daily prednisolone or steroid
equivalent for > 6 months). Subjects with asthma that require intermittent use of
bronchodilators, inhaled steroids, or local steroid injections would not be excluded
from the study.
15. Has an active systemic infection requiring therapy (e.g.: bacterial, fungal, viral).
16. Has known active Hepatitis B or C. Active Hepatitis B is defined as a known positive
HBsAg result. Active Hepatitis C is defined by a known positive Hepatitis C Antibody
result and known quantitative hepatitis C virus ribonucleic acid (RNA) results
greater than the lower limits of detection of the assay.
17. Has known psychiatric or substance abuse disorder that would interfere with
cooperation with the requirements of the trial.
18. Has interstitial lung disease or a history of pneumonitis that required oral or
intravenous steroids to assist with management. Lymphangitic spread of the NSCLC is
not exclusionary.
19. Is pregnant or breastfeeding or expecting to conceive or father children while on
study medication and for the required duration of contraception after the last dose
of study medication.
20. Has ongoing acute clinical AEs of National Cancer Institute (NCI) Common Terminology
Criteria for Adverse Events (CTCAE) Grade ≥2 resulting from prior cancer therapies
(except alopecia, peripheral neuropathy and ototoxicity, which are excluded if ≥
Grade 3).
21. Has had, within the past 6 months, the occurrence of one or more of the following
events: cerebrovascular accident, deep vein thrombosis, pulmonary embolism,
hemorrhage (CTCAE Grade 3 or 4), chronic liver disease (meeting criteria for Child
Pugh Class B or C), organ transplantation.
22. Has, within 2 weeks prior to Day 1, received systemic therapeutic doses of
corticosteroids (e.g., > 10 mg daily prednisolone or steroid equivalent). Topical,
inhaled, nasal and ophthalmic steroids are allowed for short term treatment of acute
conditions (e.g.: asthma, poison ivy contact dermatitis); for other
immunosuppressive agents, the exclusionary dose and duration will be determined in
consultation with the Medical Monitor.
23. Has any other medical or personal condition that, in the opinion of the
Investigator, may potentially compromise the safety or compliance of the patient, or
may preclude the patient's successful completion of the clinical study.
Gender:
All
Minimum age:
18 Years
Maximum age:
99 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Helen F. Graham Cancer Center (Christiana Care)
Address:
City:
Newark
Zip:
19713
Country:
United States
Facility:
Name:
Cancer Treatment Centers of America
Address:
City:
Newnan
Zip:
30265
Country:
United States
Facility:
Name:
Hematology and Oncology Clinic
Address:
City:
Baton Rouge
Zip:
70809
Country:
United States
Facility:
Name:
Sarah Cannon Research Institute
Address:
City:
Nashville
Zip:
37203
Country:
United States
Facility:
Name:
Rambam Care Campus
Address:
City:
Haifa
Country:
Israel
Facility:
Name:
Hadassah Medical Center
Address:
City:
Jerusalem
Country:
Israel
Facility:
Name:
Shaare Zedek Medical Center
Address:
City:
Jerusalem
Country:
Israel
Facility:
Name:
Hospital Clinico Universitario De Santiago De Compostela
Address:
City:
A Coruña
Country:
Spain
Facility:
Name:
NEXT Oncology Barcelona
Address:
City:
Barcelona
Country:
Spain
Facility:
Name:
Vall D'Hebron Insitute of Oncology
Address:
City:
Barcelona
Country:
Spain
Facility:
Name:
Hospital Universitario Ramon Y Cajal
Address:
City:
Madrid
Country:
Spain
Facility:
Name:
Hospital Regional Universitario de Malaga
Address:
City:
Málaga
Country:
Spain
Facility:
Name:
Hospital Quiron Madrid
Address:
City:
Pozuelo de Alarcón
Country:
Spain
Facility:
Name:
Hospital Universitario Virgen Macarena
Address:
City:
Sevilla
Country:
Spain
Facility:
Name:
INCLIVA Biomedical Research Institute
Address:
City:
Valencia
Country:
Spain
Facility:
Name:
Beatson West of Scotland Cancer Centre
Address:
City:
Glasgow
Country:
United Kingdom
Facility:
Name:
Imperial College London
Address:
City:
London
Country:
United Kingdom
Facility:
Name:
Sarah Cannon Research Institute UK (University College London Hospitals)
Address:
City:
London
Country:
United Kingdom
Facility:
Name:
The Christie NHS Foundation Trust
Address:
City:
Manchester
Country:
United Kingdom
Start date:
March 15, 2022
Completion date:
December 2023
Lead sponsor:
Agency:
Ribon Therapeutics, Inc.
Agency class:
Industry
Source:
Ribon Therapeutics, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05127590
