A Phase 1b/2 Study of Sonrotoclax (BGB-11417) as Monotherapy and in Various Combinations With Dexamethasone Plus Carfilzomib, Dexamethasone Plus Daratumumab, and Dexamethasone Plus Pomalidomide in Multiple Myeloma

Browse trials for

• Multiple Myeloma 3,627

Study arms

• Experimental
  Part 1 Dose Escalation

  Dose-escalation and de-escalation to determine maximum tolerated dose (MTD) of sonrotoclax plus dexamethasone, sonrotoclax plus dexamethasone plus carfilzomib, sonrotoclax plus dexamethasone plus daratumumab, and sonrotoclax plus dexamethasone plus pomalidomide.

  Drug: Sonrotoclax · Drug: Dexamethasone · Drug: Carfilzomib · Drug: Daratumumab · Drug: Pomalidomide

• Experimental
  Part 2 Cohort Expansion

  There will be up to 7 expansion cohorts to further evaluate the safety and efficacy of sonrotoclax monotherapy, sonrotoclax plus dexamethasone in combination with dexamethasone plus carfilzomib, and in combination with dexamethasone plus daratumumab

  Drug: Sonrotoclax · Drug: Dexamethasone · Drug: Carfilzomib

Interventions

• DrugSonrotoclax

  Administered orally daily

  Also known as: BGB-11417

• DrugDexamethasone

  Once weekly either orally or intravenously

• DrugCarfilzomib

  Administered intravenously weekly

• DrugDaratumumab

  Administered subcutaneously weekly

• DrugPomalidomide

  Administered orally daily

Primary outcomes

1. Part 1: Number Of Participants Experiencing Dose-limiting Toxicities (DLTs)

   DLTs will be based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 and will include most grade 3 or higher events, as defined in the protocol.

   Time frame: Up to 28 days

2. Part 1 And 2: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Adverse Events Leading to Discontinuation and Adverse Events of Special Interest (AESIs).

   Time frame: Up to 30 days after last dose of study drug

3. Part 2: Overall response rate (ORR) as Assessed by Investigator

   Defined as the percentage of participants who achieved a stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) per International Myeloma Working Group (IMWG) criteria

   Time frame: Approximately 4 years

4. Part 2: Very Good Partial Response (VGPR) or Better Response Rate as Assessed by Investigator

   Defined as the percentage of participants with a documented VGPR or better (including sCR, CR, and VGPR)

   Time frame: Upon study termination (Baseline up to first documentation of disease progression [PD] or death from any cause [approximately 4 years]

5. Part 2: Complete Response (CR) or Stringent Complete Response (sCR) as Assessed by Investigator

   defined as the percentage of participants with a documented CR or sCR

   Time frame: Upon study termination (Baseline up to first documentation of disease progression [PD] or death from any cause [approximately 4 years])

Secondary outcomes

1. Part 1: Area under the plasma concentration-time curve time 0 to the last measurable concentration (AUClast) After a Single Dose of Sonrotoclax

   Time frame: Cycle 1 (each cycle is up to 28 days)

2. Part 1: Maximum observed plasma concentration (Cmax) After a Single Dose of Sonrotoclax

   Time frame: Cycle 1 (each cycle is up to 28 days)

3. Part 1: Time to reach Cmax (tmax) After a Single Dose of Sonrotoclax

   Time frame: Cycle 1 (each cycle is up to 28 days)

4. Part 1: At Steady-state: AUC last, ss

   Time frame: Cycle 2 (each cycle is up to 28 days)

5. Part 1: At Steady-state: Cmax, ss

   Time frame: Cycle 2 (each cycle is up to 28 days)

6. Part 1: At Steady-state: trough plasma concentration (Ctrough) ss

   Time frame: Cycle 2 (each cycle is up to 28 days)

7. Part 1: At Steady-state: time to reach Cmax (tmax,ss)

   Time frame: Cycle 2 (each cycle is up to 28 days)

8. Part 2: Time to response (TTR) as Assessed by Investigator

   TTR is defined as the time from start of treatment (for nonrandomized cohorts) or date of randomization (for randomized cohorts to first documentation of response of Partial Response (PR) or better

   Time frame: Approximately 4 years

9. Part 2: Duration of response (DOR) as Assessed by Investigator

   DOR is defined as the time from the date of the first documented response (PR or better) after treatment initiation until the date of first documented disease progression or death due to any cause, whichever occurs first. DOR will be analyzed only for patients who have achieved an overall response of at least PR. The distribution of DOR will be summarized by the Kaplan-Meier method.

   Time frame: Approximately 4 years

10. Part 2: Progression-free survival (PFS) as Assessed by Investigator

    PFS is defined as time from start of treatment （for nonrandomized cohorts） or date of randomization （for randomized cohorts） to the first documentation of disease progression or death, whichever occurs first

    Time frame: Approximately 4 years

11. Part 2: Overall survival (OS) as Assessed by Investigator

    OS defined as the time from start of treatment (for nonrandomized cohorts) or date of randomization (for randomized cohorts to the date of death due to any cause

    Time frame: Approximately 4 years

Individual participant data

Plan to share: Yes — BeOne shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved. BeOne shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations. Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeOne review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.

Supporting information: Study protocol, Sap, Csr