JAB-21822 Activity in Adult Patients With Advanced Solid Tumors Harboring KRAS G12C Mutation

• ClinicalTrials.gov Identifier: NCT05002270
• Recruitment Status: Recruiting
• First Posted: August 12, 2021
• Last Update Posted: September 9, 2021
• Sponsor: Jacobio Pharmaceuticals Co., Ltd.
• Information provided by (Responsible Party): Jacobio Pharmaceuticals Co., Ltd.

Tracking Information

• First Submitted Date: July 26, 2021
• First Posted Date: August 12, 2021
• Last Update Posted Date: September 9, 2021
• Actual Study Start Date: September 3, 2021
• Estimated Primary Completion Date: July 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 4, 2021)

• Dose Escalation phase: Number of participants with dose limiting toxicities (DLTs) [ Time Frame: At the end of Cycle 1 (each cycle is 21 days) ]
• Dose Escalation and Dose Expansion phase: Number of participants with adverse events [ Time Frame: Up to 4 years ]
  Patients will be assessed for incidence and severity of adverse events (AEs) according to NCI-CTCAE criteria
• Dose Expansion phase: Overall response rate (ORR) [ Time Frame: Up to 4 years - from baseline to RECIST confirmed Progressive Disease ]
  ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) per RECIST v 1.1
• Dose Expansion phase: Duration of response ( DOR ) [ Time Frame: Up to 4 years ]
  DOR is defined as the time from the participant's initial objective response (CR or PR) to disease progression per CTCAE v1.1 or death due to any cause, whichever occurs first.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 4, 2021)

• Dose Escalation and Dose Expansion phase: Peak Plasma Concentration (Cmax) [ Time Frame: Up to 4 years ]
  Cmax of JAB-21822 alone or JAB-21822 plus cetuximabn will be measured by using plasma PK samples
• Dose Escalation and Dose Expansion phase: Area under the plasma concentration versus time curve (AUC) [ Time Frame: Up to 4 years ]
  AUC of JAB-21822 alone or JAB-21822 plus cetuximab will be measured by using plasma PK samples
• Dose Escalation phase: Overall response rate (ORR) [ Time Frame: Up to 4 years - from baseline to RECIST confirmed Progressive Disease ]
  The percentage of participants with complete response (CR) or partial response (PR) on RECIST v 1.1.
• Dose Escalation phase: Duration of response ( DOR ) [ Time Frame: Up to 4 years ]
  DOR is defined as the time from the participant's initial objective response (CR or PR) to disease progression per CTCAE v1.1 or death due to any cause, whichever occurs first.
• Dose Escalation and Dose Expansion phase: Disease Control Rate ( DCR ) [ Time Frame: Up to 4 years ]
  DCR is defined as percentage of participants with complete response (CR), partial response (PR), or stable disease(SD) per CTCAE v1.1
• Dose Escalation and Dose Expansion phase: Progression-free survival (PFS) [ Time Frame: Up to 4 years ]
  PFS is defined as the interval of time between the date of first treatment to the earliest date of disease progression per CTCAE v1.1 or death which occurs first

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: JAB-21822 Activity in Adult Patients With Advanced Solid Tumors Harboring KRAS G12C Mutation
• Official Title: A Phase 1/2, Multi-Center, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Evidence of Antitumor Activity of JAB-21822 Monotherapy and Combination Therapy in Adult Patients With Advanced Solid Tumors Harboring KRAS G12C Mutation
• Brief Summary: This study is to evaluate the safety and tolerability of JAB-21822 monotherapy and combination therapy in adult participants with advanced solid tumors harboring KRAS G12C mutation.
• Detailed Description: The primary objective of this study is to evaluate the safety and tolerability of JAB-21822 monotherapy to determine the MTD and PR2D during Dose Escalation phase; then to evaluate preliminary antitumor activity when JAB-21822 administered alone and combination with cetuximab during Dose Expansion phase in adult participants with advanced solid tumors harboring KRAS G12C mutation.
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Advanced Solid Tumor
• NSCLC
• CRC

Intervention

• Drug: JAB-21822 (KRAS G12C inhibitor)
  Administered orally
• Drug: Cetuximab (EGFR inhibitor)
  Administered IV

Study Arms

• Experimental: Arm A0, JAB-21822 monotherapy, Phase 1, Dose Escalation
  Dose escalation of JAB-21822 will be administered alone to determine the MTD and RP2D
  Intervention: Drug: JAB-21822 (KRAS G12C inhibitor)
• Experimental: Arm A1, JAB-21822 monotherapy, Phare 2, Dose Expansion
  JAB-21822 will be administered alone at RP2D in selected cancer type patients to evaluate the preliminary antitumor activity.
  Intervention: Drug: JAB-21822 (KRAS G12C inhibitor)
• Experimental: Experimental: Arm B, JAB-21822 combination with Cetuximab, Phase 2, Dose Expansion
  JAB-21822 will be administered together with Cetuximab in mCRC patients to evaluate the preliminary antitumor activity.
  Interventions:

  • Drug: JAB-21822 (KRAS G12C inhibitor)
  • Drug: Cetuximab (EGFR inhibitor)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 4, 2021): 100
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 2025
• Estimated Primary Completion Date: July 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Participants must be able to provide an archived tumor sample
• Histologically or cytologically confirmed solid tumors with KRAS G12C mutation
• Must have received at least 1 prior standard therapy
• Must have at least 1 measurable lesion per RECIST v1.1
• Must have adequate organ function
• Must be able to swallow and retain orally administered medication

Exclusion Criteria:

• Has brain or spinal metastases, except if treated and no evidence of radiographic progression or hemorrhage for at least 28 days
• Active infection requiring systemic treatment within 7 days
• Active HBV or HCV
• Any severe and/or uncontrolled medical conditions
• LVEF ≤50% assessed by ECHO or QTcF
• QT interval >470 msec
• Experiencing unresolved CTCAE 5.0 Grade >1 toxicities

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Huiqiang Wang, PhD; 86 10 56315466; Huiqiang.wang@jacobiopharma.com

Contact: Ramina Mikailova; ramina.mikailova@jacobiopharma.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05002270
• Other Study ID Numbers: JAB-21822-1001
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Jacobio Pharmaceuticals Co., Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: Jacobio Pharmaceuticals Co., Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Jacobio Pharmaceuticals Co., Ltd.
• Verification Date: September 2021