HFB200301 ESMO 2024 Poster.pdf
Monotherapy HFB200301 Q4W (n=27)
- DL 5 HFB (n=4)
- DL 4 HFB (n=3)
- DL 3 HFB (n=5)
Safety profiles of HFB200301 Q2W ± tislelizumab Q4W
Combination HFB200301 Q4W + tislelizumab Q4W
- Time on treatment HFB200301 trial > 4 mo (ongoing) (n=12)
- HFB200301 Q2W across all dose levels was well tolerated in monotherapy and combination with TIS on treatment Q4W without any DLTs, Grade 3 TRAEs, and TRAEs leading to discontinuation or dose modification.
- DL 4 HFB + TIS (n=3) - Similar incidence rate and severity of TRAEs commonly observed in Q4W regimen.
- DL 3 HFB + TIS (n=3)
- HFB200301 Monotherapy Q2W (n=11)
- HFB200301 Q2W + Tislelizumab Q4W (n=14)
Adverse Events
| Adverse Events | HFB200301 Monotherapy Q2W (n=11) | HFB200301 Q2W + Tislelizumab Q4W (n=14) |
|---|---|---|
| All grades n(%) | Grade 1 n(%) | Grade 2 n(%) |
| Anemia | - | - |
| Asthenia | 2(18) | 1(9) |
| Back pain | 1(9) | 1(9) |
| Chills, shivers | - | - |
| Cytokine release syndrome | 1(9) | 1(9) |
| Emesis | 1(9) | 1(9) |
| Fever | 1(9) | 1(9) |
| Hyperthyroidism | - | - |
| Hypoalbuminaemia | - | - |
| Infusion reaction | - | - |
| Mucositis oral | 1(9) | 1(9) |
| Myalgia | 1(9) | 1(9) |
| Nausea | 1(9) | 1(9) |
| Pruritus | - | - |
| Rash | 1(9) | 1(9) |
| WBC decreased | 1(9) | 1(9) |
| Weight loss | - | - |
| Xerophthalmia | - | - |
Demographics and clinical characteristics
| Characteristic | Monotherapy (n=11) | Combination (n=14) |
|---|---|---|
| Median age, years (range) | 56 (50-71) | 62.5 (37-76) |
| Women | 5 (45) | 6 (43) |
| Men | 6 (55) | 8 (57) |
| ECOG PS | 4 (40) | 5 (36) |
| 1 | 6 (60) | 9 (64) |
| Median time since initial diagnosis, years (range) | 2.2 (0.4-22.0) | 3.2 (0.7-15.8) |
| Number of prior systemic cancer therapy regimens | Median (range) | 2 (1-3) |
| Received prior anti-PD-(L)1 therapy | Yes | 8 (73) |
| No | 3 (27) | 1 (8) |
| Median follow-up time, months (range) | 2.0 (0.2-5.2) | 0.9 (0.2-3.8) |
Objectives and Study Design
Primary Objectives
- Safety and tolerability of HFB200301 in monotherapy and in combination with TIS
Secondary Objectives
- Assess PK, PD, and immunogenicity of HFB200301
- Establish RDF and BP2D
- Establish RDE and RP2D
- Examine preliminary anti-tumor efficacy, ORR using RECIST 1.1, iRECIST, and mRECIST for mesothelioma
Exploratory Objectives
- Establish Proof of Mechanism (POM) in paired tumor biopsies and peripheral blood
- Generate biomarker hypothesis for patient enrichment
Modeling and Simulation
HFB200301 model structure and fitting
PK of HFB200301 is well-described by a two-compartment model with parallel elimination via linear and non-linear clearance. Peripheral and in-tumor RO are described by direct effect models while sTNFR2 is captured by an indirect response model.
Summary and Future Directions
- Data from HFB200301 Q4W dosing enabled the successful development of PK and target engagement dosing models.
- HFB200301 Q2W dosing showed a favorable safety profile similar to that of Q4W dosing.
- The potentially improved efficacy with Q2W dosing regimen will be further evaluated in the Dose Expansion part of the clinical trial.