Phase 1
Completed N=24
Phase I/Ib Multiple Ascending Dose Study in China
Source: ClinicalTrials.gov NCT03523390 ↗Enrolled (actual)
24
Serious AEs
33.3%
Results posted
Feb 2024
Primary outcomePrimary: Number of Participants With of Dose-limiting Toxicities (DLTs) According to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) Version 4.03 — 0; 0; 0 Participants
Summary
The purpose of this study was to evaluate the maximum tolerated dose (MTD) and pharmacokinetics (PK) of Avelumab monotherapy in Chinese subjects.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With of Dose-limiting Toxicities (DLTs) According to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) Version 4.03 |
0; 0; 0 | — |
| PRIMARY Area Under the Serum Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Avelumab |
7000; 20400; 35600 | — |
| PRIMARY Area Under the Serum Concentration-Time Curve During a Dosing Interval (AUCtau) of Avelumab |
7000; 20800; 35800 | — |
| PRIMARY Area Under the Serum Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Avelumab |
7710; 22600; 38300 | — |
| PRIMARY Terminal Elimination Rate Constant (Lambda z) of Avelumab |
0.00719; 0.00767; 0.00811 | — |
| PRIMARY Maximum Observed Serum Concentration (Cmax) of Avelumab |
77.6; 294; 450 | — |
| PRIMARY Last Quantifiable Serum Concentration (Clast) of Avelumab |
4.94; 16.3; 21.4 | — |
| PRIMARY Serum Trough Concentration Levels (Ctrough) of Avelumab |
4.94; 14.8; 21.4 | — |
| PRIMARY Time to Reach Maximum Observed Serum Concentration (Tmax) of Avelumab |
1.55; 1.52; 1.97 | — |
| PRIMARY Apparent Terminal Half Life (t1/2) of Avelumab |
96.5; 90.3; 85.5 | — |
| PRIMARY Dose Normalized Area Under the Serum Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t/Dose) of Avelumab |
2330; 2040; 1780 | — |
| PRIMARY Dose Normalized Area Under the Concentration-Time Curve Over the Dosing Interval (AUCtau/Dose) of Avelumab |
2330; 2080; 1790 | — |
| PRIMARY Dose Normalized Maximum Observed Serum Concentration (Cmax/Dose) of Avelumab |
25.9; 29.4; 22.5 | — |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Related TEAEs According to National Cancer Institute- Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) |
3; 7; 6; 8; 3; 6 | — |
| SECONDARY Number of Participants With at Least 1 Positive Anti-Avelumab Antibodies (ADA) |
2; 0; 0; 0 | — |
Eligibility Criteria
Inclusion Criteria
- Signed written informed consent prior to any study-related procedures are undertaken that are not part of standard patient management
- Histologically or cytologically proven locally advanced unresectable or metastatic solid tumors, for which no standard therapy exists or standard therapy has failed
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at study entry
- Availability of a recently obtained formalin-fixed, paraffin-embedded block containing tumor tissue (biopsy from a non-irradiated area within 6 months) or 12 or more unstained tumor slides suitable for biomarker detection
- Other protocol defined inclusion criteria could apply
Exclusion Criteria
- Prior therapy with any antibody/drug targeting T-cell coregulatory proteins (immune checkpoints) such as programmed death 1 (PD-1), PD-L1, cytotoxic T-lymphocyte antigen-4 (CTLA-4), 4-1BB, Lymphocyte-activation gene 3 (LAG-3), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) or anti-Cluster of Differentiation (CD)-127
- Persisting toxicity related to prior therapy (Grade greater than equals to [>=] 2 National Cancer Institute- Common Terminology Criteria for Adverse Events [NCI-CTCAE] v4.03, except Grade less than [ = 3 NCI-CTCAE v4.03)
- Active brain metastases (except those treated locally, and have not been progressing for at least 2 weeks after the completion of therapy, with no steroid maintenance therapy required, and no ongoing neurological symptoms related to brain localization of the disease)
- Any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma)
- Other protocol defined exclusion criteria could apply
Data sourced from ClinicalTrials.gov (NCT03523390). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.