Study of JDQ443 in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation

Condition(s) studied

Investigational drug(s) / intervention(s)

JDQ443: KRAS G12C inhibitor

TNO155: SHP2 inhibitor

tislelizumab: Anti PD1 antibody

Study summary

This is a phase Ib/II open label study. The escalation part will characterize the safety and tolerability of JDQ443 single agent and JDQ443 in combination with the other study treatments (TNO155 and tislelizumab) in advanced solid tumor patients. After the determination of the maximum tolerated dose / recommended dose for a particular treatment arm, dose expansion will assess the anti-tumor activity and further assess the safety, tolerability, and PK/PD of each regimen at the maximum tolerated dose / recommended dose or lower dose.

Eligibility

Primary outcome measure(s)

• Dose Escalation: Incidence and severity of dose limiting toxicities (DLTs) during the first cycle of monotherapy or combination treatment — 21 days
  A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment
• Dose Escalation: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) — 24 months
  All information obtained on AE will be displayed by treatment group. Summary tables will include only AEs that started/worsened during the cycles of treatment (treatment-emergent AEs).
• Dose Escalation: Frequency of dose interruptions and reductions, by treatment — 24 months
  Tolerability of study drug will be assessed by summarizing the number of and reason for dose delays and dose reductions.
• Dose Escalation: Dose intensity by treatment — 24 months
  Dose intensity is defined as the ratio of actual cumulative dose received and actual duration of treatment.
• Dose Expansion: Overall response rate (ORR) per RECIST v1.1, by treatment — 24 months
  Overall response rate is defined as the proportion of patients with a BOR of CR or PR according to RECIST 1.1, and will be summarized along with the corresponding 95% exact binomial confidence interval (CI). Applies to all groups except the brain metastasis group.
• Dose expansion: Overall intracranial response rate (OIRR) per mRANO-BM — 24 months
  OIRR per mRANO-BM is defined as the proportion of participants with a best overall intracranial response (BOIR) of CR or PR according to mRANO-BM criteria, and will be summarized along with the corresponding 90% and 95% exact CI. Applies to brain metastasis group only.
• Dose expansion: Incidence and severity of AEs and SAEs — 24 months
  All information obtained on AE will be displayed by treatment group. Summary tables will include only AEs that started/worsened during the cycles of treatment (treatment-emergent AEs). Applies to JDQ443 dose randomization group only.
• Dose expansion: frequency of dose interruptions and reductions, by treatment — 24 months
  Tolerability of study drug will be assessed by summarizing the number of and reason for dose delays and dose reductions. Applies to JDQ443 dose randomization group only.
• Dose expansion: Dose intensity by treatment — 24 months
  Dose intensity is defined as the ratio of actual cumulative dose received and actual duration of treatment. Applies to JDQ443 dose randomization group only
• Dose expansion: ORR per RECIST 1.1 of JDQ443 single agent in patients with non-small cell lung cancer (JDQ443 dose randomization group only) — 24 months
  Overall response rate is defined as the proportion of patients with BOR of CR or PR according to RECIST 1.1, and will be summarized along with the corresponding 95% exact binomial confidence interval (CI). Applies to JDQ443 dose randomization group only

Trial sites (38)

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