HFB200603 ESMO 2024 Poster.pdf
DL 2 HFB (n=1)
DL 1 HFB (n=1)
Overview
- DL (Dose Level)
- HFB (HFB200603)
- Q3W (once every 3 weeks)
- TIS (tislelizumab)
Adverse Events
| Adverse Event | HFB200603 (Monotherapy) | HFB200603 + TIS |
|---|---|---|
| Nausea | 1 (6) | 1 (6) |
| Intratumoral CD8+ T cell | Ongoing > 6 mo | |
| Oral dryness | 1 (4) | 1 (4) |
| Palmar erythema | 1 (4) | 1 (4) |
| Platelet count decreased | 3 (12) | 3 (12) |
| Pruritus | 3 (12) | 1 (4) 2 (8) |
| Rash | 2 (8) | 2 (8) |
! ! !
Trial Summary
HFB200603 was well tolerated in monotherapy and in combination with tislelizumab with no DLTs and no TRAEs leading to dose modification or drug discontinuation.
Disease Cell Atlas scRNA of tumors refractory to IO:
- Example from clear cell renal cell carcinoma (52k tumor immune cells)
- HFB200603 PK is favorable for immune antagonism
- HFB200603 exposures are linear, dose-dependent, and similar to those projected from preclinical studies.
! ! !
Monotherapy Summary
Monotherapy • HFB200603 shows a favorable safety profile and demonstrates a dose-dependent PK and PD both as a monotherapy and in combination with TIS in subjects with heavily pre-treated refractory solid tumors.
Research Findings
BTLA and PD-1 in exhausted CD8+ T cells:
- Consistent with an inhibitory role of BTLA in these cells.
- Using bulk RNA expression databases, the expression of BTLA and its ligand HVEM (TNFRSF14) was assessed, showing potential benefit from combination treatment.
The DIS® platform was used to select tumor types most likely to respond to HFB200603 based on target biology and single-cell insights.
Objectives and Study Design
Primary Objectives
- Examine preliminary anti-tumor efficacy, ORR using RECIST 1.1 and iRECIST
- Establish RDEs and RP2D
Secondary Objective
- Assess PK, PD, and immunogenicity of HFB200603
Exploratory Objective
- Establish Proof of Mechanism (POM) in paired tumor biopsies and peripheral blood
Key Eligibility Criteria
- Adult patients with advanced or metastatic solid tumors, including:
- Clear cell renal cell carcinoma
- PD-L1+ colorectal cancer
- PD-L1+ gastric cancer
- PD-L1+ melanoma
- PD-L1+ non-small cell lung cancer
- Measurable disease - RECIST 1.1
- Patient must have exhausted standard lines of systemic therapy
Treatment Related Adverse Events (N=42)
| Adverse Event | HFB200603 Monotherapy (N) | HFB200603+TIS (N=25) |
|---|---|---|
| Asthenia | 4 (24) | 1 (4) |
| Diarrhea | 1 (6) | 2 (8) |
| Fatigue | - | 1 (4) |
| Nausea | 1 (6) | 1 (4) |
| Oral dryness | - | 1 (4) |
| Palmar erythema | - | 1 (4) |
| Platelet count decreased | - | 3 (12) |
| Pruritus | - | 3 (12) |
| Rash | - | 2 (8) |
Immune Activation Results
Peripheral flow cytometry analysis revealed that the proliferating (Ki67+) cell fractions of CD4+ and CD8+ T cells showed moderate expansion following HFB200603 treatment, both as monotherapy and in combination with tislelizumab (Wilcoxon test p<0.05).
Disease Control Rate (DCR)
- 65% per RECIST 1.1
- Evidence of mechanism in the tumor context
- DCR includes stable disease (SD), partial response (PR) and complete response (CR) in target lesion per RECIST 1.1
Acknowledgments
Using DIS® guided enrichment of tumor types, we generated compelling proof-of-mechanism data reinforcing our confidence in HFB200603, demonstrated by observed clinical activity and associated predictive biomarkers.
Preliminary clinical activity in liver metastases across several heavily pre-treated tumor types, including MSS-CRC, ccRCC, and gastric cancer, is encouraging and will be further explored in the Dose Expansion part of the trial.