Relapsed, extended-stage disease small cell lung cancer (ED SCLC). MedDRA version: 20.0 Level: LLT Classification code 10041071 Term: Small cell lung cancer stage unspecified System Organ Class: 100000004864
Conditions
Interventions
Product Name: ORY-1001.2HCl
Product Code: PEI 13-106
Pharmaceutical Form: Powder for oral solution
INN or Proposed INN: ORY-1001
CAS Number: 1431303-72-8
Other descriptive name: ORY-1001
Concentration
Sponsors
Oryzon Genomics S. A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age = 18 years. 2. Patients who present a relapse = 3 months and are candidate to re-challenge with platinum-based chemotherapy (TFI>90 days). 3. Patient must have histologically- or cytologically-confirmed diagnosis of SCLC. Archival primary tumor tissue (formalin-fixed paraffin-embedded (FFPE) tissue is acceptable) should be provided to analyse predictive biomarkers. 4. Positive results to ORY-1001 candidate predictive biomarkers confirmed by central laboratory through primary archival tumor tissue analysis. 5. Patients with ECOG Performance Status 0-2. 6. Patients with life expectancy of at least 12 weeks. 7. Patients with measurable lesions according to RECIST criteria 1.1. 8. Patients with an adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) =1500 cells/µL, platelet count =100,000 cells/µL and hemoglobin =9 g/dL. 9. Patients with preserved hepatic function: bilirubin =1.5 X ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =3.0 X ULN. 10. Patients with preserved renal function: serum creatinine 60mL/min. 11. Patient must be able to swallow and retain orally administered study treatment. 12. For women of childbearing potential: Agreement to remain abstinent (refrain from heterosexual intercourse) or use one highly effective (less than 1% failure rate) method of contraception during the treatment period and for at least 28 days after the last dose of ORY-1001. • A woman is considered to be of childbearing potential if she is post-menarcheal, has not reached a post-menopausal state (= 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). • Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, established proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intra-uterine devices, and copper intra-uterine devices. • The reliability of sexual abstinence should be evaluated in relation to the duration of clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of contraception. For men: Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below: • With female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for at least 4 months after the last dose of ORY-1001 to avoid exposing the embryo. Men must refrain from donating sperm during this same period. • The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence and withdrawal are not acceptable methods of contraception. 13. Patients with ability to understand the requirements of the study, provide written informed consent and authorization of use and disclosure of protected health information, and agree to abide by the study restrictions and to return for the required assessments. Are the trial subjects under 18? no Number of subjects
Exclusion criteria
Exclusion criteria: 1. Patients with symptomatic and/or unstable pre-existing brain metastases; has known active central nervous system (CNS) metastases. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. 2. Patients with other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or cervical cancer in situ. 3. Patients who currently participate or have participated in a study of an investigational agent or are using an investigational device within 28 days of the first dose of treatment. 4. Patients who have had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events due to a previously administered agent. 5. Patiens who have undergone major surgery, he/she must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. 6. Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study including: • Unstable angina, symptomatic or otherwise uncontrolled arrhythmia (does not include stable, lone atrial fibrillation), QTcF > 480 ms based on the average of 3 screening electrocardiograms (ECGs), uncontrolled hypertension, symptomatic congestive heart failure (NYHA II, III, IV), myocardial infarction = 6 months prior to first study treatment,serious uncontrolled cardiac arrhythmia, cerebrovascular accidents = 6 months before study treatment start. • Any active (acute or chronic) or uncontrolled infection/disorders that impair the ability to evaluate the patient or for the patient to complete the study. • Non-malignant medical illnesses that are uncontrolled or whose control may be • Jeopardized by this study treatment, such as, severe diabetes mellitus that is not controlled with medical management. 7. Patients with evidence of interstitial lung disease, or history of (non-infectious) pneumonitis that required steroids, or current pneumonitis. 8. Patients with evidence of electrolyte imbalance, such as hypokalemia, hyperkalemia, hypocalcemia, hypercalcemia, hypomagnesemia, and hypermagnesemia of Grade > 1, as per NCI CTCAE, version 5.0. Treatment for correction of above electrolyte imbalances is permitted during screening to meet eligibility. 9. Patients who refuse to potentially receive blood products and/or have a hypersensitivity to blood products. 10. A physical exam or laboratory finding that contraindicates the use of investigational therapy or otherwise places the patient at excessively high risk for treatment, as determined by the Investigator. 11. Patients with known bone marrow disorders which may interfere with bone marrow recovery (i.e., tumor involvement, fibrosis), or patients with delayed recovery from prior chemoradiotherapy (i.e., after radiation to the pelvis). 12. Patients with known coagulopathy, platelet disorder or history of non-drug-induced thrombocytopenia. 13. Patients with known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the maximum tolerated dose (MTD), schedule and recommended Phase II dose (RP2D) of ORY-1001 in combination with platinum-etoposide based chemotherapy (EP) in patients with relapsed, extensive-stage disease small cell lung cancer (ED SCLC). This will include characterization of ORY-1001 dose-limiting toxicities (DLTs) and overall safety profile in this population.;Secondary Objective: -Tumor response according to RECIST v1.1 -Duration of Response: the time from the first response (PR or CR) to disease progression or death from any cause, whichever occurs first -Time to progression: the time from first study treatment to disease progression -Time to response: the time from first study treatment to either a CR or PR -Objective Response: partial response plus complete response, confirmed by repeat assessments = 4 weeks after initial documentation -Progression-Free Survival: the time from first study treatment to the first occurrence of disease progression or death, whichever occurs first -Overall Survival: the time from first study treatment, the length of time the patient is alive -To monitor ORY-1001 exposure and accumulation at steady state -To monitor ORY-1001 pharmacodynamics in terms of LSD1 target engagement (PD/TE) in peripheral blood mononuclear cells;Primary end point(s): To asses safety, tolerability and dose finding of combo therapy;Timepoint(s) of evaluation of this end point: For a maximum of 4-6 cycles according to investigator criteria, or until disease progression/treatment failure, or unacceptable toxicity or study discontinuation, whichever occurs the first. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Tumor response according to RECIST version 1.1 2. Duration of Response (DOR) of combo therapy 3. Time to progression (TTP) of combo therapy 4. Time to response (TTR) of combo therapy 5. Objective Response (OR ) of combo therapy 6. Progression-Free Survival (PFS) of combo therapy 7. Overall Survival (OS) of combo therapy 8. To monitor ORY-1001 exposure and accumulation at steady state (PK) 9. To monitor ORY-1001 pharmacodynamics in terms of LSD1 target engagement (PD/TE) in peripheral blood mononuclear cells (PBMCs);Timepoint(s) of evaluation of this end point: For a maximum of 4-6 cycles according to investigator criteria, or until disease progression/treatment failure, or unacceptable toxicity or study discontinuation, whichever occurs the first. | — |
Countries
Spain
Contacts
Public ContactRoger Bullock
Oryzon Genomics S. A.
Outcome results
None listed