ZN-c3 in Adult Participants With Metastatic Colorectal Cancer
- Conditions
- metastatic colorectal cancerMedDRA version: 21.0Level: LLTClassification code: 10052362Term: Metastatic colorectal cancer Class: 10029104Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2022-502267-37-00
- Lead Sponsor
- K-Group Beta Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 82
Male or female participants minimum legal adult age or =18 years (whichever is greater) at the time of informed consent., Adequate bone marrow function characterized by the following at screening: a. ANC =1.5 × 109/L (excluding measurements obtained within 7 days after daily administration of filgrastim/sargramostim or within 3 weeks after administration of pegfilgrastim, as applicable). b. Platelets =100 × 109/L(excluding measurements obtained within 3 days after transfusion of platelets). c. Hemoglobin =9.0 g/dL (excluding measurements obtained within 2 weeks after blood transfusion)., Adequate hepatic and renal function characterized by the following at screening: a. Serum Total bili = 1.5 x upper limit of normal ULN and ? 2 mg/dL. Note: Total bili > 1.5 x ULN is allowed if direct (conjugated) = 1.5 x ULN and indirect (unconjugated) bilirubin is = 4.25 x ULN. Note: Participants with hyperbilirubinemia due to non-hepatic cause (eg, hemolysis, hematoma) may be enrolled following discussion and agreement with the medical monitor. b. AST and ALT = 2.5 x ULN, or = 5.0 × ULN in the presence of liver metastases. c. Adequate renal function defined by an estimated creatinine clearance =50 mL/min according to the Cockcroft Gault formula or by 24-hour urine collection for creatinine clearance, or according to local institutional standard method. d. Adequate electrolytes, defined as serum potassium and magnesium levels within institutional normal limits. Note: Replacement treatment to achieve adequate electrolytes will be allowed., Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol., Body weight = 40 kg., Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures., Histologically or cytologically confirmed metastatic Stage IV colorectal adenocarcinoma., Documented evidence of a BRAF V600E mutation in tumor tissue or blood (ie, ctDNA) as previously determined by PCR or NGS-based laboratory assay, or a CE-marked assay for Europe, in a CLIA or similarly certified laboratory. (A molecular report clearly documenting the presence of the BRAF V600E mutation (and other molecular findings from sample analysis as performed during the normal course of clinical care) must be provided for confirmation that testing meets eligibility during Screening.), Presence of measurable disease per RECIST version 1.1 guidelines, as assessed by investigator and evidenced by available baseline tumor scan., Confirmation of availability of adequate tumor tissue (primary or metastatic; archival or newly obtained; block or slides) which may be used for retrospective analysis of BRAF V600E mutation status. Tumor sample can be archival or de novo (newly collected fixed biopsy sample) and must be in an FFPE block or provide a minimum of 15-20 unstained slides of analyzable tissue. Participants with <15 unstained slides may also be considered eligible after consultation with Sponsor or designee. Whenever possible, the archival sample should be from the same tumor block that was used for local BRAF V600E mutation testing. It is recommended that the tissue block be obtained from a biopsy or surgery that was performed within 2 years prior to study enrollment. Please consult the study clinician to determine if samples are older and/or if there are fewer than the required number of slides w
Documented clinical disease progression (eg, worsening of performance status, clinical symptoms, or clinically significant laboratory parameters demonstrating worsening of disease) or radiographic disease progression during the screening period., History or current evidence of congenital or known family history of LQTS or TdP., Evidence of active noninfectious pneumonitis., Evidence of active and uncontrolled bacterial or viral infection within 2 weeks prior to start of any of the study interventions, with certain exceptions, as noted below, for chronic infection with HIV, HBV or HCV. Participants with an infection receiving treatment (antibiotic, antifungal, or antiviral treatment) must have completed such treatment and the infection must be considered controlled/resolved by the investigator at least 2 weeks before start of any of the study interventions. Note: For COVID-19/SARS-CoV-2, SARS-CoV-2 testing is not mandated for study entry, and testing should follow local clinical practice standards. Any participant with a positive test result for SARS-CoV-2 infection during screening, is known to have asymptomatic infection or is suspected of having SARS-CoV-2, is excluded. Once the infection resolves, the participant may be considered for re-screening., Participants with known positivity for HIV (testing is not required unless mandated locally) are ineligible unless they meet all of the following: a. A stable regimen of highly active anti-retroviral therapy that is not contraindicated; b. No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections; c. A CD4 count >250 cells/mcL, and an undetectable HIV viral load on standard PCR-based tests, Active hepatitis B or hepatitis C infection (testing not required unless mandated locally) a. Active HBV is defined as any of the following: • HBsAg(+), HBV DNA >200 IU/mL. • HBsAg(+), HBV DNA =200 IU/mL and persistent or intermittent elevation of ALT/AST (eg, above normal range) and/or liver biopsy showing chronic hepatitis with moderate or severe necroinflammation. Note: Participants who are HBsAg(-), HBcAb(+) are eligible and should be monitored/treated as per local standard of care. b. Active HCV is defined as: • HCV antibody positive; AND • Presence of HCV RNA., Concurrent or previous other malignancy within 2 years of study entry, except curatively treated basal or squamous cell skin cancer, prostate intraepithelial neoplasm, carcinoma in-situ of the cervix, Bowen’s disease or prostate cancer with a Gleason score =6. Participants with a history of other curatively treated malignancies with low risk of recurrence not listed may also be considered eligible after consultation with Sponsor or designee., Residual NCI CTCAE v5.0 = Grade 2 toxicity from any prior anticancer therapy, with the exception of Grade 2 alopecia or Grade 2 neuropathy., Other severe acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or administration of any of the study interventions or, in the investigator’s judgment, make the participant inappropriate for the study., Dose Escalation part: Prior therapy with any WEE1 inhibitor. Dose Expansion part: Prior therapy with any WEE1 inhibitor or any selective BRAFi inhibitor (eg, encorafenib, dabrafenib, vemurafenib, XL281/BMS-908662) or any EGFR inhibitor (eg, cetuximab, panitumumab
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