AACR 2020 | The efficacy and safety of geptanolimab (GB226) in patients with R/R PTCL

Peripheral T-cell lymphoma (PTCL) is a heterogeneous disease associated with poor prognosis. In Western countries, PTCL accounts for 5–10% of non-Hodgkin lymphomas, with a higher incidence in China (25–30%).¹ Despite the recent development of several novel agents, including anti-CD30 immunoconjugate, antifolate and histone deacetylase inhibitors, patients with relapsed or refractory (R/R) disease experience modest improvement in clinical outcomes. Therefore, the need for a more active treatment remains.

One of the features of PTCL is overexpression of programmed death-ligand 1 (PD-L1). Yuankai Shi and colleagues explored whether targeting PD-L1 with a monoclonal antibody against PD-1, geptanolimab (GB226), could improve outcomes of patients with R/R PTCL. The efficacy and safety results of this multicenter, open-label, single-arm, phase II trial (NCT03502629) were presented during the American Association for Cancer Research (AACR) Virtual Annual Meeting I 2020.¹

Study design

• In total, 102 patients were enrolled in the study between July 8, 2018, and August 2019
• Eligibility criteria included
  • Age ≥ 18 years
  • Histological diagnosis of PTCL
  • R/R PTCL after systematic treatment
  • Eastern Cooperative Oncology Group (ECOG) score 0–1
• Patients received an intravenous infusion of geptanolimab 3 mg/kg once every two weeks until disease progression, death, unacceptable toxicity or withdrawal of consent
• Study endpoints:
  • Primary

• • • Objective response rate (ORR) by the independent review committee (IRC) according to Lugano 2014 criteria

• • Secondary

• • • Duration of response (DOR)
    • Disease control rate (DCR)
    • Progression-free survival (PFS)
    • Overall survival (OS)
    • Time to response (TTR)
    • Safety
    • Immunogenicity
  • Exploratory
    • Correlative biomarker analysis

Results

• The date for data cut off was November 1, 2019
• Out of 102 patients who received treatment
  • 26 patients continued with treatment
  • 76 patients were withdrawn from treatment. Reasons for continuation are presented in Figure 1

Figure 1. Reasons for treatment discontinuation.

Patient characteristics

Patients and disease characteristics are presented in Table 1

Table 1. Baseline patient and disease characteristics Characteristics Geptanolimab (N = 102) Median age (range), years 52.5 (18–78) Male gender, % 68.6

Prior lines of treatment, %

1

2

≥ 3

41.2

33.3

25.5

Stage of disease, %

I–II

III–IV

16.7

82.4

PTCL subtype, %

PTCL-NOS

ALCL ALK+

ALCL ALK-

ENKTL

Other

38.2

6.9

11.8

21.6

21.6

ALCL, anaplastic large cell lymphoma; ENKTL, extranodal NK/T-cell lymphoma nasal type; NK, natural killer; PTCL, peripheral T-cell lymphoma; PTCL-NOS, PTCL-not otherwise specified

Efficacy

• Based on IRC assessment disease control rate (DCR) was 55.9% and ORR was 36.3% (Overall efficacy is presented in Table 2)
  • The highest DCR was seen in patients with anaplastic large cell lymphoma (ALCL) ALK+, extranodal NK/T-cell lymphoma nasal type (ENKTL), and ALK- (71.4%, 68.2%, and 66.7%, respectively)
  • The highest ORR was seen in patients with ALCL ALK- and ALK+, as well as ENKTL (58.3%, 42.9% and 40.9%, respectively)
• Median PFS by IRC evaluation was 2.69 (1.74–4.21) months
  • PFS rate at 3 months was 44.1% (95% CI, 33.8–53.9)
  • PFS rate at 6 months was 38.6% (95% CI, 28.5–48.7)
• Median overall survival by IRC evaluation was not reached (NR, 8.15 months–NR)

Table 2. Overall geptanolimab efficacy at data cut off

Efficacy	Investigator assessed (N = 102)	IRC assessed (N = 102)
Best overall response, % CR PR SD PD Unable to evaluate Not evaluated	6.9 28.4 18.6 35.2 1.0 9.8	10.8 25.5 19.6 33.3 0 10.8
ORR (95% CI), %* All subsets PTCL-NOS ENKTL ALCL ALK+ ALCL ALK- Others	35.3 (26.09–45.38) NA NA NA NA NA	36.3 (26.96–46.39) 28.2 40.9 42.9 58.3 31.8
DCR (95% CI), %† All subsets PTCL-NOS ENKTL ALCL ALK+ ALCL ALK- Others	53.9 (43.77–63.84) NA NA NA NA NA	55.9 (45.71–65.71) 46.2 68.2 71.4 66.7 50.0
Medium DOR (95% CI), months	4.14 (1.45–NR)	6.83 (5.13–NR)
Medium TTR (95% CI), months	2.79 (2.66–5.65)	4.04 (1.48–8.25)
ALCL, anaplastic large cell lymphoma; CI, confidence interval; CR, complete response; DCR, disease control rate; DOR, duration of response; ENKTL, extranodal NK/T-cell lymphoma nasal type; IRC, independent review committee; NA, not assessed; NR, not reached; ORR, objective response rate; PD, progressive disease; PR, partial response; PTCL-NOS, peripheral T-cell lymphoma not otherwise specified; SD, stable disease; TTR, time to response *defined as CR + PR  †defined as CR + PR + SD

 

• Subgroup analysis revealed:
  • Patients with ≤ 2 previous lines of therapy compared to those with > 2 had higher DCR (59.2% vs 46.2%) and median PFS (2.9 vs 1.4 months)
    • There was no impact on ORR
  • Patients with previous exposure to chidamide (a new histone deacetylase inhibitor approved in China for treatment of PTCL after front-line failure) compared to those without had lower DCR (45.8% vs 59.0%) and longer median PFS (4 vs 2.7 months)
    • There was no impact ORR
  • Patients with a history of ASCT had higher ORR (57.1%) compared those without (34.7%)
    • There was no impact on DCR or PFS
  • Higher PD-L1 positivity score (≥ 50 vs <50) correlated with enhanced
    • ORR (46.0% vs 24.4%)
    • DCR (64.0% vs 43.9%)
    • Median PFS (6.2 vs 1.5 months)
    • Median DOR (NR vs 6.8 months)

Safety

• Treatment-emergent adverse events (TEAEs) of any Grade were experienced by 92.2% of patients, including Grade ≥ 3 by 55.9% of patients
• TEAEs Grade ≥ 3 were reported in 23.5% of patients, with lymphocytopenia, thrombocytopenia, and anemia being the most common (3.9%, 3.9%, and 2%, respectively
• Serious adverse events (SAEs) were experienced by 38.2% of patients,
  • 15.7% of SAEs were treatment-related
• Immune-related AEs were present in 35.3% of patients, including 10.8% with Grade ≥ 3, with pulmonary infection, pulmonary inflammation skin rash, and pruritus the most common Grade ≥ 3 (2%, 1%, 1%, and 1%, respectively)
• TEAEs led to treatment discontinuation in 20.6% of patients and death in 4.9% of patients

Conclusion

The results of the study demonstrate that geptanolimab has promising clinical activity in patients with R/R PTCL. The benefit was seen across different subtypes, with ORR especially high in ALCL and ENKTL. The correlation of response with the level of PD-L1 expression suggests that this could be used to select patients most likely to respond. The safety profile was manageable. However, further studies evaluating efficacy and safety are needed.