Phase 1: Advanced solid tumors, relapsed or refractory to standard therapy Phase 2: non-small cell lung cancer, metastatic colorectal cancer, and other solid tumors MedDRA version: 21.1 Level: LLT Classification code 10065252 Term: Solid tumor System Organ Class: 100000004864
Conditions
Interventions
Product Name: JAB-21822
Product Code: JAB-21822
Pharmaceutical Form: Tablet
INN or Proposed INN: Not available
CAS Number: Not availabl
Current Sponsor code: JAB-21822
Other descriptive name: JAB-2182
Sponsors
Jacobio Pharmaceuticals Co., Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -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
Exclusion criteria
Exclusion criteria: -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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Dose Escalation Phase (Phase 1): - To evaluate the overall safety and tolerability of JAB-21822 monotherapy - To determine the maximum tolerated dose and a recommended Phase 2 dose of JAB-21822 monotherapy administered once daily in participants with relapsed or refractory solid tumors with KRAS G12C mutation Dose Expansion Phase (Phase 2): - To further evaluate preliminary antitumor activity, objective response rate, and duration of response of JAB-21822 monotherapy at the recommended Phase 2 dose in participants with relapsed and refractory non-small cell cancer and other solid tumors with KRAS G12C mutation, and in combination with cetuximab in metastatic colorectal cancer with KRAS G12C mutation;Secondary Objective: Dose Escalation Phase (Phase 1): - To evaluate preliminary antitumor activity of various dose levels of JAB-21822 monotherapy in participants with relapsed and refractory solid tumors with KRAS G12C mutation - To characterize the pharmacokinetic(s) profiles of JAB-21822 after a single dose and at steady state after multiple doses Dose Expansion Phase (Phase 2): - To determine progression-free survival, overall survival, time to response, and disease control rate - To further assess the overall safety and tolerability of JAB-21822 at the recommended Phase 2 dose as monotherapy and in combination with cetuximab - To further characterize the pharmacokinetic(s) profiles of JAB-21822 with sparse sampling using a population pharmacokinetic(s) analysis approach;Primary end point(s): Dose Escalation Phase (Phase 1): - Safety and tolerability of repeated cycles from first drug administration up to the end of the follow-up period o Incidence, nature, and severity of treatment-emergent adverse events, treatment-related adverse events, and death per National Cancer Institute Common Terminology Criteria for Adverse Events Version 5 - Treatment-emergent changes in clinical laboratory measurements, electrocardiogram findings, vital signs, Eastern | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Dose Escalation Phase (Phase 1): - Objective response rate defined as the percentage of participants with partial response or complete response based on RECIST v1.1 - disease control rate, time to response, duration of response, and progression-free survival - PK parameters of JAB-21822 including, but not limited to, Cmax, tmax, Ctrough, AUC0-t, AUC0-t, AUC0-inf, t½, CL/F, Vz/F, Rac Cmax, and Rac AUC Dose Expansion Phase (Phase 2): - progression-free survival and time to response - overall survival - disease control rate - Safety and tolerability of repeated cycles from first drug administration up to the end of the follow-up period o Incidence, nature, and severity of treatment-emergent adverse events, treatment-related adverse events, and death per National Cancer Institute Common Terminology Criteria for Adverse Events Version 5 - Treatment-emergent changes in clinical laboratory measurements, ECG findings, vital signs, Eastern Cooperative Oncology Group performance status, and physical examination findings -PK parameters of JAB-21822 and potential factors (covariates) that impact the PK parameters;Timepoint(s) of evaluation of this end point: -Dose Escalation and Dose Expansion phase: Peak Plasma Concentration (Cmax); Time Frame: Up to 4 years -Dose Escalation and Dose Expansion phase: Area under the plasma concentration versus time curve; Time Frame: Up to 4 years -Dose Escalation phase: Overall response rate; Time Frame: Up to 4 years - from baseline to RECIST confirmed Progressive Disease -Dose Escalation phase: Duration of response; Time Frame: Up to 4 years -Dose Escalation and Dose Expansion phase: Disease Control Rate; Time Frame: Up to 4 years -Dose Escalation and Dose Expansion phase: Progression-free survival; Time Frame: Up to 4 years | — |
Countries
Hungary, Israel, Poland, Spain, United States
Contacts
Public ContactJAB-21822-1001 clinical team
Jacobio Pharmaceuticals Co., Ltd.
Outcome results
None listed