Pretreated mismatch-repair-proficient and microsatellite stable metastatic colorectal cancer (pMMR–MSS metastatic CRC). MedDRA version: 21.0 Level: PT Classification code 10052358 Term: Colorectal cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: -
Product Code: [CR6086]
Pharmaceutical Form: Capsule, hard
CAS Number: 1417742-86-9
Current Sponsor code: CR6086Z
Concentration unit: mg milligram(s)
Concentration type: equal
Concentra
Sponsors
ROTTAPHARM BIOTECH S.R.L.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed and dated informed consent obtained before undergoing any study-specific procedure 2. Male or female aged =18 years 3. Histologically confirmed diagnosis of adenocarcinoma originating from the colon or rectum, with known RAS and BRAF mutational status as assessed per standard practice 4. Stage IV (according to the American Joint Committee on Cancer definition) 5. Presence of measurable disease per RECIST v1.1 (based on imaging within 28 days from first study drug administration). Patients must have at least one "target lesion" to be used to assess response, as defined by RECIST v1.1 Note: Subjects with lesions in a previously irradiated field as the sole site of measurable disease will be permitted to enroll provided the lesion(s) have demonstrated clear progression and can be measured accurately 6. Disease progression after at least two standard treatment lines for mCRC, including fluoropyrimidines, oxaliplatin and irinotecan and, if RAS and BRAF wild-type, cetuximab or panitumumab, or, intolerance or refusal of chemotherapy regimens for mCRC Note: Previous oxaliplatin-based adjuvant treatment is considered as a treatment line if disease relapse occurred within 6 months from its completion 7. Naïve to any antibody/drug targeting T-cell co-regulatory proteins (immune checkpoints inhibitors) and EP4 receptor antagonists 8. Availability of adequate and sufficient baseline tumor tissue sample (archival or newly obtained biopsy) Note: an adequate and sufficient sample is defined as formalin fixed paraffin embedded tumor tissue sample, preferably from the most recent biopsy of a tumor lesion, collected either at the time of or after the diagnosis of metastatic disease has been made AND from a site not previously irradiated. If no tumor tissue is available, a fresh tissue from needle or excisional biopsy or from resection is required 9. pMMR/MSS defined as CRC with all 4 MMR proteins intact AND with instability at =1/5 locus (or 30% of loci if larger panel of markers are assayed) 10. Eastern Cooperative Oncology Group (ECOG) performance status of = 1 11. Anticipated life expectancy = 3 months 12. Adequate hematologic and end organ function, defined by the following laboratory results, obtained within 7 days before first dose of study drug treatment: a. Hemoglobin = 10 g/dL, platelet count =100,000/mm3, ANC =1500/mm3 b. Creatinine clearance = 50 mL/min c. Amylase and lipase = 1.5 × ULN d. Serum bilirubin = 1.5× ULN e. AST, ALT, and ALP = 2.5 × ULN with the following exceptions: - Patients with documented liver metastases: AST and/or ALT = 5 × ULN f. INR and PTT = 1.5 × ULN. - Patients who are on therapeutic doses of anti-coagulants should be on a stable dose for 28 days, with stable INR and PTT values. g. Serum albumin = 3.0 g/dL h. Proteinuria = 3.5 g/24 hours 13. Ability e and willingness to participate and comply with the requirements of the entire study Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 17
Exclusion criteria
Exclusion criteria: Medical Condition/History: Cancer and anti-cancer therapy: 1. Additional malignancy that progressed or required active treatment within the last 2 years. Exceptions include basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin that has undergone potentially curative therapy with no evidence of recurrence for 5 years since initiation of that curative therapy, or carcinoma in situ (breast carcinoma, cervical cancer) 2. Active brain tumor, metastasis or leptomeningeal metastases. Patients with brain metastases are eligible if these have been treated and there is no magnetic resonance imaging (MRI except where contraindicated in which CT scan is acceptable) evidence of progression for at least 8 weeks after treatment is complete and within 28 days prior to first dose of study drug administration. Cases should be discussed with the Sponsor. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (>10mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration 3. Major surgery within 28 days before Cycle 1 Day 1 or anticipation of needing such procedure during the trial 4. Treatment with any systemic or localized anti-cancer therapy, including chemotherapy, biological therapy, radiotherapy, or hormonal therapy within 28 days before initiation of Cycle 1 Day 1 or expected to required such a treatment during the trial 5. Persistent toxicity related to prior therapy, Grade >1 according to NCI CTCAE Version 5.0 Note 1: Patients must have recovered from all AEs due to previous therapies, to CTCAE =Grade 1 or to baseline condition. Participants with CTCAE =Grade 2 neuropathy or alopecia may be eligible Note 2: If patients received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment Note 3: 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 6. Uncontrolled tumor-related pain. Patients requiring narcotic pain medication must be on a stable regimen at study entry 7. Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated drainage more than once every 28 days. Indwelling drainage catheters are allowed Cardiovascular: 8. Unstable angina 9. Myocardial infarction within 6 months before enrolment 10. History of stroke, reversible ischemic neurological defect, or transient ischemic attack within 6 months before enrolment 11. Uncontrolled ventricular arrhythmia 12. Congestive heart failure (New York Hearth Association class =II) 13. Poorly controlled hypertension Infections: 14. Confirmed infection with SARS-CoV-2 as documented by molecular testing at nasopharyngeal swab 15. HIV infection 16. Active tuberculosis 17. Acute or chronic viral hepatitis B or C infection 18. Any severe infection within 14 days before Cycle 1 Day 1 General Medical History: 19. Active autoimmune disease in the past 2 years 20. History of allogenic tissue/solid organ transplant (including allogeneic bone marrow transplantation) 21. History of immunodeficiency. Please refer to the protocol for further exclusion criteria.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To evaluate the therapeutic potential of CR6086 in combination with ICIs (here represented by the PD-1 inhibitor AGEN2034) in the treatment of pMMR–MSS metastatic CRC, assessed when all patients at the highest Dose Level tested have completed 24 weeks of treatment, unless they discontinued earlier, based on: - The safety and tolerability of the combination in the target population - The preliminary efficacy of the combination in the target population as determined by the Disease Control Rate (DCR). 2. To select the best performing dose of CR6086 to be recommended for future combination studies in immuno-oncology indications, according to the parameters above.;Secondary Objective: 1. To further assess the preliminary anti-tumor activity of the combination in terms of Objective Response Rate (ORR), Duration Of Response (DOR), Progression-Free Survival (PFS), Progression-Free Survival Rate (PFSR) and Overall Survival (OS), in the target population throughout the study. 2. To investigate the sustained safety and tolerability of the combination throughout the study.;Primary end point(s): Safety and tolerability: 1. Incidence of DLTs 2. Incidence of TEAEs 3. Incidence of SAEs 4. Changes in clinical laboratory parameters, vital signs, ECOG performance status, ECG and physical examination Efficacy: 1. Disease Control Rate (DCR) 2. Objective Response Rate (ORR) Please refer to the protocol for further endpoints.;Timepoint(s) of evaluation of this end point: Safety and tolerability: 1. Through the first 2 cycles (4 weeks) 2. While patients are on treatment or up to 30 days after the last dose of last study treatment 3. While patients are on treatment or up to 90 days after the last dose of last study treatment or to a minimum of 30 days after the last IMP intake in case of initiation of new anti-cancer therapy, whichever occurs first 4. From baseline to the 30-day Follow-up visit Efficacy: 1. When patients have achieved CR, PR, or stable disease (SD) 2. W | — |
Countries
Italy
Contacts
Public ContactDipartimento Medico
OPIS s.r.l.
Outcome results
None listed