A clinical study to assess the effects of RBN-2397 and pembrolizumab in patients with lung cancer (Squamous Cell Carcinoma of the Lung)
- Conditions
- Advanced/metastatic NSCLC of squamous cell histologyMedDRA version: 24.0Level: LLTClassification code 10085300Term: Squamous non-small cell lung cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2021-003829-30-ES
- Lead Sponsor
- Ribon Therapeutics, Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 50
1. Male or female patients 18 years or older.
2. Confirmed diagnosis of advanced/metastatic NSCLC of squamous cell histology as determined by local testing practices:
a. Patients should have received prior therapy including a platinum doublet 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.
and
b. The last regimen prior to enrolling in the study must be an approved checkpoint inhibitor-containing regimen where the best response was stable disease (SD), partial response (PR), or complete response (CR).
Note: Combination of anti-PD-1/anti-PD-L1 and anti-CTLA-4 are considered one line of therapy.
3. Patients experienced PD as determined by the investigator during or following their most recent treatment regimen. Supporting information about PD must be documented.
4. Patient will have provided signed and dated informed consent prior to initiation of any study procedures.
5. Patient agrees to undergo biopsy for fresh tissue sample collection, provided the procedure to obtain the biopsy is deemed a non-significant risk procedure and is safe to do so. Patient consent for tumor biopsy collection (during Screening) is mandatory.
a. Archival biopsy samples collected within 12 weeks prior to Screening are acceptable as the baseline biopsy.
b. In the event that collection of a fresh biopsy is not medically feasible or in cases where the fresh biopsy is deemed not evaluable (e.g., no tumor present), submission of an archival sample collected >12 weeks prior to Screening may be requested.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
7. Have CT or MRI imaging done within 28 days prior to study treatment and have at least one measurable target lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
8. Patient has adequate organ function as specified by the following laboratory values:
a. Patient has adequate renal function (creatinine < or = 1.5 × the upper limit of normal [ULN]) or a glomerular filtration rate (GFR) of > or = 60 mL/min/1.73 m2).
b. Patient has adequate hepatic function, as evidenced by a total bilirubin < or = 1.5 × ULN (unless due to Gilbert’s Syndrome who are excluded if total bilirubin > 3.0 × ULN and direct bilirubin > 1.5 × ULN), aspartate aminotransferase (AST), and /or alanine aminotransferase (ALT) < or = 2.5 × ULN or < or = 5 × ULN, if due to liver involvement by tumor.
c. Patient has adequate bone marrow function, as evidenced by hemoglobin > or = 9.0 g/dL in the absence of transfusion within the previous 72 hours, platelet count > or = 100 × 10^9cells/L, and absolute neutrophil count (ANC) > or = 1.5 × 10^9 cells/L. The requirement for an ANC > or = 1.5 × 10^9/L must be independent of recent growth factor support (e.g., within the last 7 days).
9. Patient and his/her partner agree to use adequate contraception after providing written informed consent through 4 months after the last study drug dose, as follows:
a. For women: Negative pregnancy test during Screening and compliant with a medically approved contraceptive regimen during and for 4 months after the treatment period or documented to be surgically sterile or postmenopausal. The use of hormonal contraception (oral or implanted) is not considered a medically approved regimen, as RBN-2397 may interfere with the efficacy of hormonal based contraception.
b. For men: Compliant with a
1. Has non-squamous histology NSCLC. Patients whose tumors have a mixed histology are ineligible.
2. Must not have received any other investigational systemic therapy for SCCL.
3. Should not have received more than 2 prior lines of therapy with ICI including anti-PD-1/anti-PD-L1, anti-CTLA-4 inhibitors and 1 prior line of a chemotherapy doublet treatment.
4. Unable to swallow oral medications, has impairment of gastrointestinal (GI) function or GI disease that may significantly alter drug absorption.
5. 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 (< or = 2 weeks of radiotherapy) to non-CNS disease.
6. Symptomatic or has uncontrolled brain metastases, leptomeningeal disease, or spinal cord compression not definitively treated with surgery or radiation.
7. Has discontinued prior treatment with an ICI due to irAEs.
8. Has a known history of prior malignancy. Except: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; completely resected basal cell and squamous c ell skin cancers; any malignancy considered to be indolent and that has never required therapy; and completely resected carcinoma in situ of any type.
9. Has received a live-virus vaccination within 30 days of planned treatment start.
10. 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 arrhythmias, or electrocardiographic evidence of acute ischemia.
11. Has a history of prolonged QT syndrome or Torsades de pointes, and/or has a familial history of prolonged QT syndrome.
12. 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.
13. Ingestion of herbal medicines within 3 weeks before Screening, and grapefruit, grapefruit juice, pomegranate juice, star fruit, tangelos, or orange marmalade (made with Seville oranges) within 1 week prior to Screening.
14. Has active autoimmune disease that has required systemic treatment in the past 12 months
15. Is on chronic systemic steroids
16. Has an active systemic infection requiring therapy.
17. Has known active Hepatitis B or C.
18. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient’s participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator.
19. Has known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial.
20. Has interstitial lung disease or a history of pneumonitis that required oral or IV steroids to assist with management.
21. Is pregnant or breastfeeding
22. Has ongoing acute clinical AEs CTCAE > or = G2 resulting from prior cancer therapies
23. Has had, within the past 6 months, the occurrence of one or more of the following events: cerebrovascular accident,
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method