IBI322 Shows Early Antitumor Efficacy in PD-1/PD-L1–Resistant Classical Hodgkin Lymphoma

Single-agent IBI322 elicited responses with favorable safety in patients with classical Hodgkin lymphoma that had become resistant to anti–PD-1/PD-L1 therapy, according to data from a phase 1 trial (NCT04795128) presented at the 2023 EHA Congress.¹

In all patients (n = 23), IBI322 monotherapy elicited an objective response rate (ORR) of 47.8% (95% CI, 26.8%-69.4%); this included a complete response (CR) rate of 17.4%, a partial response (PR) rate of 30.4%, and a stable disease (SD) rate of 43.5%. Moreover, 8.7% of patients experienced disease progression. The disease control rate (DCR) in this population was 91.3% (95% CI, 72.0%-98.9%).

In the subset of patients with primary-resistant disease (n = 7), IBI322 induced an ORR of 57.1% (95% CI, 18.4%-90.1%), which included a 42.9% CR rate, a 14.3% PR rate, and a 28.6% SD rate; the PD rate was 14.3%. In this group, the DCR was 85.7% (95% CI, 42.1%-99.6%).

“IBI322 monotherapy showed a promising antitumor effectivity with a manageable safety profile in [patients with] anti–PD-1 or –PD-L1 treatment-resistant classical Hodgkin lymphoma,” Jingwei Yu, MD, PhD, of Tianjin Medical University Cancer Institute & Hospital in Tianjin, China, said in a presentation of the data.

Although treatment with PD-1 or PD-L1 inhibitors and brentuximab vedotin (Adcetris) has proven to be effective in the treatment of patients with relapsed or refractory classical Hodgkin lymphoma, some patients still progress. Those who do are known to have a poor prognosis; as such, novel options are needed.

The anti-CD47/PD-L1 bispecific antibody is designed to block the PD-1/PD-L1 and CD47/SIRP-α pathways. Preclinical findings have indicated that the agent bines to CD47 and PD-L1–positive tumor cells which may substantially decrease the toxicity to red blood cells.

The early-phase trial enrolled patients with histologically confirmed classical Hodgkin lymphoma who were at least 18 years of age, had an ECOG performance status ranging from 0 to 2, had at least 1 evaluable lesion, and were resistant to PD-1 or PD-L1 therapy.

Study participants received intravenous IBI322 at 45 mg/kg every 2 weeks. Treatment was continued up to 24 months, until progressive disease, unacceptable toxicity, withdrawn consent, or if other reasons for discontinuation were met. The primary objective of the research was to evaluate the safety and antitumor activity of IBI322 by Lugano 2014 criteria.

In the 24 patients enrolled, the median age was 35 years (range, 25-68) and 70.8% were male. Regarding Ann Arbor stage, 16.7% had stage II disease, 37.5% had stage III disease, 37.5% had stage IV disease, and this information was missing for 8.3% of patients. Most patients had an ECOG performance status of 0 (62.5%) and the remainder had a status of 1 (37.5%). Notably, 33.3% of patients were primary resistant to anti–PD-1/PD-L1 therapy and 66.7% were secondary resistant. Additionally, 16.7% previously received brentuximab vedotin.

In his presentation, Yu shared the case of a male patient who was 25 years of age and who had nodular sclerosis classical Hodgkin lymphoma that was stage IV. The patient had received treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or AVD with a PD-1 antibody between June 2020 and November 2020. From February 2021 to June 2021, the patient was given a PD-1 antibody in combination with decitabine, and in September 2021, they received GDPE. In November 2021, the patient was given brentuximab vedotin or brentuximab vedotin plus ICE.

They began treatment with IBI322 in January 2022 and achieved a CR after 2 treatment cycles. Notably, no grade 3 or higher treatment-related adverse effects (TRAEs) were reported. Grade 2 TRAEs included an increase in creatine kinase and aspartate aminotransferase. Grade 1 TRAEs comprised increased white blood cell count, neutrophil count, C-reactive protein, hematuria, and urine leukocyte, amylase, and cholinesterase. The patient continues to be on study and in a CR.

Regarding safety, 91.7% of patients experienced any-grade TRAEs and 41.7% experienced grade 3 or higher TRAEs. The most common TRAEs experienced by at least 10% of patients included decreased lymphocyte count (any grade, 62.5%; grade 3 or higher, 29.2%), anemia (62.5%; 0%), decreased white blood cell count (20.8%; 0%), decreased platelet count (20.8%; 4.2%), hypophosphatemia (16.7%; 0%), increased alanine aminotransferase (12.5%; 0%), increased aspartate aminotransferase (12.5%; 0%), increased blood creatinine phosphokinase (12.5%; 0%), increase C-reactive protein (12.5%; 0%), presence of protein urine (12.5%; 0%), increased blood bilirubin (12.5%; 0%), increase blood creatinine (12.5%; 0%), presence of urinary casts (12.5%; 0%), and pyrexia (12.5%; 0%).

Any-grade immune-related AEs occurred in 16.7% of patients.

Dr Yu has no affiliations to disclose.

Reference

Zhang H, Yu J, Li H, et al. CD47/PD-L1 bispecific antibody (IBI322) in anti-PD-1 or PD-L1 treatment-resistant classical Hodgkin lymphoma: a phase 1 study. Presented at: 2023 EHA Congress; June 8-11, 2023; Frankfurt, Germany. Abstract S216.