A First-in-Human Study of BG-C0979 in Adults With Advanced Solid Tumors

Keywords

• ADAM9 (disintegrin and metalloproteinase 9)
• antibody-drug conjugate

Lead sponsor

BeOne Medicines is the lead sponsor of 61 studies on the registry; 42 are open to participants now.

Of its 6 completed or terminated interventional studies of FDA-regulated products, 0 (0%) have results posted.

Study arms

• Experimental
  Phase 1a: Monotherapy Dose Escalation

  Participants will receive increasing doses of BG-C0979 as monotherapy.

  Drug: BG-C0979

• Experimental
  Phase 1a: Monotherapy Safety Expansion

  Participants will receive BG-C0979 as monotherapy. Selected dose levels that have been determined to be safe in Phase 1a dose escalation will be further evaluated in safety expansion.

  Drug: BG-C0979

• Experimental
  Phase 1b, Part A: Monotherapy Dose Optimization and Dose Expansion

  Participants will receive BG-C0979 as monotherapy in a dose optimization and dose expansion phase at different dose levels of recommended doses for expansion (RDFEs) identified in Phase 1a.

  Drug: BG-C0979

• Experimental
  Phase 1b, Part B: Combination Therapy Expansion

  Participants will receive BG-C0979 in combination with tislelizumab in select tumor types.

  Drug: BG-C0979 · Drug: Tislelizumab

Interventions

• DrugBG-C0979

  Administered by intravenous infusion.

• DrugTislelizumab

  Administered by intravenous infusion.

  Also known as: BGB-A317

Primary outcomes

1. Phase 1a: Number of Participants Experiencing Adverse Events (AEs)

   Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including dose limiting toxicities (DLTs), AEs meeting protocol-defined adverse event of clinical interest (AECI) criteria, laboratory values, and electrocardiogram results.

   Time frame: Up to approximately 24 months

2. Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BG-C0979 Monotherapy

   MTD or MAD, defined as the highest dose for which the estimated toxicity rate is closest to the target toxicity rate of 28%, or the highest dose administered, respectively.

   Time frame: Up to approximately 10 months

3. Phase 1a: Recommended Dose(s) for Expansion (RDFE[s])

   The potential RDFE(s) of BG-C0979 will be determined based on the totality of data including the MTD or MAD, long-term tolerability, pharmacokinetics (PK), preliminary antitumor activity, and any other relevant data, as available.

   Time frame: Up to approximately 10 months

4. Phase 1b: Recommended Phase 2 Dose (RP2D)

   RP2D of BG-C0979 alone and in combination with tislelizumab will be determined based on safety, PK, preliminary antitumor activity, and other relevant data, as available.

   Time frame: Up to approximately 24 months

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

   ORR as determined from tumor assessment by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. For castration-resistant prostate cancer (CRPC), ORR will be assessed by RECIST v1.1 criteria for soft tissue and Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria for bone lesions. ORR is defined as the percentage of participants with best overall response of a complete response (CR) or partial response (PR).

   Time frame: Up to approximately 24 months

Secondary outcomes

1. Phase 1a: ORR

   ORR as determined from tumor assessment by the investigator using RECIST v1.1. For CRPC, ORR will be assessed by RECIST v1.1 criteria for soft tissue and PCWG3 criteria for bone lesions. ORR is defined as the percentage of participants with best overall response of a complete response (CR) or partial response (PR).

   Time frame: Up to approximately 24 months

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

   DOR as determined from tumor assessment by the investigator using RECIST v1.1. For CRPC, DOR will be assessed by RECIST v1.1 criteria for soft tissue and PCWG3 criteria for bone lesions. DOR is defined as the time from the first determination of an objective response until the first documentation of disease progression or death due to any cause, whichever occurs first.

   Time frame: Up to approximately 24 months

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

   DCR as determined from tumor assessment by the investigator using RECIST v1.1. For CRPC, DCR will be assessed by RECIST v1.1 criteria for soft tissue and PCWG3 criteria for bone lesions. DCR is defined as the percentage of participants with best overall response of a CR, PR, or stable disease.

   Time frame: Up to approximately 24 months

4. Phase 1a: Plasma Concentration of BG-C0979

   Time frame: Up to approximately 3 months

5. Phase 1a: Area Under the Concentration-Time Curve (AUC) for BG-C0979

   Time frame: Up to approximately 3 months

6. Phase 1a: Maximum Observed Concentration (Cmax) of BG-C0979

   Time frame: Up to approximately 3 months

7. Phase 1a: Time to Maximum Concentration (Tmax) of BG-C0979

   Time frame: Up to approximately 3 months

8. Phase 1b: Number of Participants Experiencing Adverse Events (AEs)

   Number of participants with TEAEs and SAEs, including AECIs, laboratory values, and electrocardiogram results.

   Time frame: Up to approximately 24 months

9. Phase 1b: Progression-Free Survival

   PFS is defined as the time from the date of the first administration of study drug(s) to the date of the first documentation of disease progression or death due to any cause, whichever occurs first.

   Time frame: Up to approximately 24 months

10. Phase 1b: Radiographic Progression-Free Survival (rPFS) for Participants with CRPC

    rPFS is defined as the time from the date of the first administration of study drug(s) to the date of the first objective evidence of radiographic disease progression or death due to any cause, whichever occurs first.

    Time frame: Up to approximately 24 months

11. Prostate-Specific Antigen (PSA) Response for Participants with CRPC

    PSA response is defined as a ≥50% decrease in PSA level from baseline to the lowest post-baseline PSA result, confirmed by a second consecutive PSA assessment at least 3 weeks later.

    Time frame: Up to approximately 24 months

12. Phase 1b: Plasma Concentration of BG-C0979, Alone and in Combination with Tislelizumab

    Time frame: Up to approximately 3 months

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