Pipeline

ABL111

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  • Pipeline
    ABL111 (Givastomig)
  • Program Target
    Claudin18.2x4-1BB
  • Disease Indication
    Solid Tumor
  • Development Stage
    Clinical Development
    (Phase 1)
Summary
ABL111 is a bispecific antibody combining Claudin18.2, a gastric- and pancreatic-specific cancer antigen with 4-1BB agonistic activity to supercharge T cells in a Claudin18.2-dependent manner, enhancing anti-tumor immunity while minimizing 4-1BB related toxicity. ABL111 is full length anti-Claudin18.2 mAb (Fc-silenced human IgG1) fused with scFv of anti-4-1BB engaging mAb. ABL111 possesses unique properties that 4-1BB activation signal is dependent on Claudin18.2 expression. ABL111 shows superior anti-tumor activity in an animal model system than Claudin18.2 alone, 4-1BB alone or combination of both with immunological memory resistant to rechallenge with same tumors.

Superior anti-tumor efficacy in patients with a wide range of expression levels

Efficacy

  • Total of 55 subjects enrolled: 21 GC (20 CLDN18.2+), 2 GEJ (2 CLDN18.2+), 5 EAC (4 CLDN18.2+), 14 PDAC (8 CLDN18.2+), and 13 other various types of cancers (2 CLDN18.2+).
  • Of the 26 patients with GC/GEJ/EAC whose tumors were CLDN18.2+, 20 patients were efficacy evaluable and dosed at 5, 8, 12, and 15mg/kg. Partial response (PR) was observed in 3 out of 20 subjects that included 1 at 5mg/kg (CLDN18.2 IHC 1+, 10%; 2+, 1%), 1 at 8mg/kg (CLDN18.2 IHC 1+, 20%; 2+, 30%), and 1 at 12mg/kg (CLDN18.2 IHC 2+, 10%; 3+, 90%). All three PR occurred at the time of first tumor assessment (8 weeks). Two responding patients had received prior anti-PD-(L)1 therapy, both concluding approximately 4 months before starting givastomig (Figure 4A and 4B).
  • Stable disease (SD) was also observed in 4 out of the 20 efficacy evaluable patients. One patient had a PR on the first scan and subsequently withdrew from the study, meeting criteria for SD.
  • An additional PR was observed in one patient with head and neck squamous cell carcinoma receiving 12mg/kg, who remains on study at 280 days.
Superior anti-tumor efficacy in patients with a wide range of expression levels
좌우스크롤 Superior anti-tumor efficacy in patients with a wide range of expression levels

Excellent safety of 4-1BB T cell engager bispecific antibody

Safety

  • No DLT was reported up to 15mg/kg, and MTD was not reached.
  • The most commonly reported TRAEs (reported from >10% of subjects) were Grade 1 or 2 nausea (23.6%), vomiting (16.4%), fatigue (14.5%), and anemia (10.9%).
  • 10 subjects (18.2%) experienced at least one Grade 3 TRAE. No Grade 3 TRAEs occurred in more than 1 subject.
  • Event onset of gastrointestinal TRAEs were generally after 14 days of treatment and recovered within 1 week; none led to drug withdrawal.

Table 2: Treatment-related Adverse Events (TRAEs) Occurred in ≥5% (N=55)

좌우스크롤
Preferred Term Grade 1
n (%)		 Grade 2
n (%)		 Grade 3
n (%)		 Grade 4
n (%)		 Grade 5
n (%)		 All Grades
n (%)
Nausea 10 (18.2) 3 (5.5) 0 0 0 13 (23.6)
Vomiting 7(12.7) 2 (3.6) 0 0 0 9 (16.4)
Fatigue 7(12.7) 1 (1.8) 0 0 0 8 (14.5)
Anemia 1(1.8) 4 (7.3) 1(1.8) 0 0 6 (10.9)
Abdominal pain 2(3.6) 1 (1.8) 0 0 0 3 (5.5)
Alanine aminotransferase increased 2(3.6) 0 1(1.8) 0 0 3 (5.5)
Diarrhea 3(5.5) 0 0 0 0 3 (5.5)
Headache 1(1.8) 2(3.6) 0 0 0 3 (5.5)
Lymphocyte count decreased 1(1.8) 1(1.8) 1(1.8) 0 0 3 (5.5)
Pruritus 2(3.6) 0 1(1.8) 0 0 3 (5.5)
Pyrexia 3(5.5) 0 0 0 0 3 (5.5)
White blood cell count decreased 0 2(3.6) 1(1.8) 0 0 3 (5.5)

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