A Study Investigating BGB-26808 Alone or in Combination With Tislelizumab in Participants With Advanced Solid Tumors

Keywords

• advanced solid tumor
• BGB-26808
• BGB-A317
• Tislelizumab
• PD1
• HPK1

Study arms

• Experimental
  Phase 1a: Dose Escalation

  Sequential cohorts of increasing dose levels of BGB-26808 will be evaluated as monotherapy and in combination with tislelizumab.

  Drug: BGB-26808 · Drug: Tislelizumab

• Experimental
  Phase 1b: Dose Expansion

  Recommended doses for expansion (RDFEs) for BGB-26808 from Phase 1a in combination with tislelizumab plus chemotherapy will be evaluated.

  Drug: BGB-26808 · Drug: Tislelizumab · Drug: Chemotherapy

Interventions

• DrugBGB-26808

  Planned doses administered orally as a tablet daily.

• DrugTislelizumab

  Planned doses administered by intravenous infusion.

  Also known as: BGB-A317

• DrugChemotherapy

  Administered in accordance with relevant local guidelines and/or prescribing information.

Primary outcomes

1. Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

   Number of participants with AEs and SAEs, including findings from physical examinations, electrocardiograms (ECGs), laboratory assessments, and that meet protocol-defined dose-limiting toxicity criteria.

   Time frame: From the first dose of study drug(s) to 90 days after the last dose or initiation of a new anticancer therapy, whichever occurs first; up to approximately 12 months

2. Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-26808

   MTD is defined as the highest dose evaluated for which estimated toxicity rate is the closest to the target toxicity rate. MAD is defined as the highest dose administered if MTD is not reached.

   Time frame: Approximately 1 month

3. Phase 1a: Recommended Dose for Expansion (RDFE) of BGB-26808

   RDFE of BGB-26808 alone or in combination with tislelizumab will be determined based upon the MTD or MAD.

   Time frame: Approximately 1 month

4. Phase 1b: Overall Response Rate (ORR)

   ORR is defined as the percentage of participants who had confirmed complete response (CR) or partial response (PR) assessed by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

   Time frame: Approximately 6 months

Secondary outcomes

1. Phase 1a: ORR

   ORR is defined as the percentage of participants who had confirmed complete response (CR) or partial response (PR) assessed by the investigator using RECIST v1.1.

   Time frame: Approximately 6 months

2. Phase 1a and 1b: Duration of Response (DOR)

   DOR is defined as the time from the first determination of an objective response per RECIST v1.1 until the first documentation of disease progression or death, whichever occurs first as assessed by the investigator.

   Time frame: Approximately 9 months

3. Phase 1a and 1b: Disease Control Rate (DCR)

   DCR is defined as the percentage of participants with best overall response of CR, PR, or stable disease. It will be summarized similarly as ORR as assessed by the investigator.

   Time frame: Approximately 6 months

4. Phase 1a and 1b: Clinical Benefit Rate (CBR)

   CBR is defined as the percentage of participants with best overall response of confirmed CR, PR, or stable disease lasting ≥ 24 weeks as assessed by investigator.

   Time frame: Approximately 6 months

5. Phase 1b: Progression Free Survival (PFS)

   PFS is defined as the time from the date of the first dose of study drug(s) to the date of the first documentation of progressive disease assessed by the investigator using RECIST v1.1 or death, whichever occurs first.

   Time frame: Approximately 9 months

6. Phase 1a and 1b: Plasma concentrations of BGB-26808

   Time frame: Approximately 6 months

7. Phase 1a and 1b: Maximum observed plasma concentration (Cmax) for BGB-26808

   Time frame: Approximately 1 month

8. Phase 1a and 1b: Time to maximum plasma concentration (Tmax) for BGB-26808

   Pharmacokinetic analysis for BGB-26808 concentrations, alone or in combination with tislelizumab. Single-dose and steady-state PK parameters.

   Time frame: Approximately 1 month

9. Phase 1a and 1b: Area under the concentration-time curve (AUC) for BGB-26808

   Time frame: Approximately 1 month

10. Phase 1b: Number of Participants with AEs and SAEs

    Number of participants with AEs and SAEs, including findings from physical examinations, ECGs, laboratory assessments, and that meet protocol-defined dose-limiting toxicity criteria.

    Time frame: From the first dose of study drug(s) to 90 days after the last dose or initiation of a new anticancer therapy, whichever occurs first; up to approximately 12 months

Individual participant data

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Supporting information: Study protocol, Sap, Csr