Study to investigate JAB-21822 Monotherapy and Combination Therapy in Adult Patients with Advanced Solid Tumors Harboring KRAS G12C Mutatio
- Conditions
- Phase 1: Advanced solid tumors, relapsed or refractory to standard therapyPhase 2: non-small cell lung cancer, metastatic colorectal cancer, and other solid tumorsMedDRA version: 21.1Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2021-003028-34-HU
- Lead Sponsor
- Jacobio Pharmaceuticals Co., Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 136
-Written ICF must be signed and dated by the participant prior to the performance of any study-specific procedures, sampling, or analyses.
-=18 years of age at the time of signing the ICF.
-ECOG performance status score of 0 or 1.
-Life expectancy =3 months.
-Participant must be able to provide an archived tumor sample or tumor tissue from a newly obtained biopsy from the tumor site which has not been previously irradiated.
-Histologically or cytologically confirmed solid tumors with KRAS G12C mutation by laboratories, which are either CLIA certified or recognized by local institution, and meets the following criteria:
Phase 1; Cohort A0
a.Have histologically or cytologically confirmed metastatic or locally advanced
solid tumor that is not a candidate for curative intervention.
b.Must have received at least 1 prior standard therapy for their tumor type and stage.
Phase 2; Cohort A1, A2 and Cohort B1, B2
A1:
a.Has histologically or cytologically confirmed diagnosis of unresectable Stage
IIIB or Stage IV NSCLC and is not a candidate for curative intervention.
b.Must have received a platinum-based therapy and an immune checkpoint
inhibitor unless such therapies are contraindicated or not available to the participant or the participant refused them. No more than 4 previous systemic regimens for the metastatic disease are allowed.
c.Participant with actionable mutations must have received appropriate targeted therapies available per local standard unless such therapies are contraindicated or not available to the participant or the participant refused them. No more than 3 previous systemic regimens for the metastatic disease are allowed.
d.Had received adjuvant or neoadjuvant chemotherapy and had
recurrence/progression on or within 6 months of completion of the therapy is
allowed to count the therapy as 1 previous regimen for the metastatic disease.
e.KRAS G12C inhibitors naïve.
A2:
a.KRAS G12C inhibitors naïve.
For mCRC:
b.Have histologically or cytologically confirmed mCRC that is not a candidate
for curative intervention.
c.Have received no more than 4 prior systemic regimens of standard therapy for mCRC per local treatment standard deemed to be appropriate by the
investigator unless such therapies are contraindicated, intolerable, or the
participant refused them.
d.Systemic regimens should include a fluoropyrimidine, irinotecan, and oxaliplatin.
e.For mCRC participants with MSI-H disease, must have prior systemic
regimens with checkpoint inhibitor unless such are contraindicated or not available to the participant or the participant refused them.
f.Participant who had received adjuvant or neoadjuvant chemotherapy and had recurrence/progression on or within 6 months of completion of the therapy is allowed to count the therapy as 1 previous regimen for the metastatic disease.
For all other solid tumors:
g.Have histologically or cytologically confirmed metastatic or locally advanced
solid tumor except NSCLC that is not a candidate for curative intervention.
h.Must have received at least 1 prior standard therapy for their tumor type and stage.
Cohort B:
a.Cohort B:
i.B1: KRAS G12C inhibitors naïve mCRC.
ii.B2: KRAS G12C inhibitors treated mCRC.
b.Have histologically or cytologically confirmed mCRC that is not a candidate
for curative intervention.
c.Has received no more than 4 prior systemic regimens of standard therapy for mCRC per local treatment standard deemed to be appropriate by the
investigator unless such therapies are contraindicate
-Participant has a history of solid tumor or hematological malignancy that is histologically distinct from the cancers under study, except for cervical carcinoma in situ, superficial noninvasive bladder tumors, breast ductal carcinoma in situ, prostatic intraepithelial neoplasia without evidence of prostate cancer, or curatively treated Stage I nonmelanoma skin cancer.
-Participant has known serious allergy to cetuximab (Cohort B1 and B2 only) or to a G12C inhibitor (Cohort A0 and B2 only).
-Participant has brain or spinal metastases except if treated by surgery, surgery plus radiotherapy or radiotherapy alone, with no evidence of radiographic progression or hemorrhage for at least 28 days before the start of treatment with the study drugs, and if applicable, on stable dose of systemic corticosteroids for at least 28 days before the start of treatment with the study drugs.
-Active infection requiring systemic treatment at the start of treatment in this trial.
-Participants testing positive for HIV are NOT excluded from this study, but HIV positive participants must meet certain criteria.
-Has active HBV or HCV.
Note:Participants with HBV who have controlled infection (serum HBV DNA PCR that is below the limit of detection) are permitted. Participants with controlled infections must undergo periodic monitoring of HBV DNA.
Note:Participants who are HCV antibody positive who have controlled infection may be enrolled into the study. Participants with controlled infections must undergo periodic monitoring of HCV RNA by their treating physician.
-History (=6 months before the start of treatment) of any severe and/or uncontrolled medical conditions or other conditions that, in the opinion of the investigator and sponsor, could affect the participant’s participation in the study.
-History (=6 months before the start of treatment with the study drugs) of any of the following: acute myocardial infarction, unstable angina pectoris, coronary artery bypass graft, or cerebrovascular accident.
-Participants who have impaired cardiac function or clinically significant cardiac
diseases.
-Participants with QT interval >470 msec at Screening using QTcF, determined as the mean of 3 QTcF values from the screening triplicate ECG.
-Participants experiencing unresolved Grade >1 toxicity before the start of treatment with the study drug except for hair loss (alopecia) and stable Grade 2 toxicities (stable defined as more than 3 months, if permitted by the investigator and medical monitor).
-Women who are pregnant or breast-feeding.
-Has received or will receive a live vaccine within 30 days prior to the first
administration of study medication. Seasonal flu vaccines that do not contain live vaccine are permitted.
-Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
-History of an allogeneic bone marrow or solid organ transplant.
-Use of systemic anticancer agent or investigational drug is prohibited =28 days for biologics and IV chemotherapy, or =21 days or 5 half-lives (whichever is longer) for small molecules prior to the first dose of JAB-21822.
-History of radiation therapy =14 days prior to the first dose of study drug.
-Prophylactic administration of G-CSF, filgrastim, pegfilgrastim, blood transfusion, platelet packets, and erythropoietin are not allowed during =4 weeks before the start of treatment and during Cycle 1 of the Dose Escalation Phase.
-Use of drugs known to be moderate
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