TJ-L14B/ABL503 Showcases Early Efficacy Signals in Advanced or Metastatic Solid Tumors

Sang Hoon Lee

TJ-L14B/ABL503 demonstrated preliminary efficacy signals in the form of responses in patients with progressive, locally advanced or metastatic solid tumors who were relapsed or refractory after previous lines of therapy, according to data from an ongoing phase 1 trial (NCT04762641).¹

To date, investigators have observed 1 complete response, 1 partial response, and 2 unconfirmed objective responses with the differentiated PD-L1 x 4-1BB bispecific antibody. The maximum tolerated dose has not yet been reached.

The dose-expansion portion of the trial is ongoing in the United States and South Korea, and I-Mab expects to share top-line data from the trial at a medical meeting in the first half of 2024.

“We’re encouraged by these early results of TJ-L14B/ABL503 as they continue to demonstrate the potential of this highly differentiated treatment for tumor types with significant unmet need,” Raj Kannan, chief executive officer of I-Mab, stated in a press release. “With the success of patent registrations across multiple countries, and promising preliminary data from the phase 1 study, we’re reaffirming the possibility for TJ-L14B/ABL503 to make a significant impact on the lives of people with cancer. We look forward to sharing more progress on the global development of TJ-L14B/ABL503.”

TJ-L14B/ABL503 is comprised of a PD-L1 arm, which serves as the tumor-dependent T-cell activator, and the 4-1BB arm, which serves as the conditional T-cell activator upon tumor engagement.² The product utilizes ABL Bio, Inc.’s Grabody-T bispecific antibody platform technology to fuel the activation of 4-1BB only in tumor cells that express PD-L1 to reduce the risk of off-tumor toxicity.

Preclinical data presented at the 2021 SITC Annual Meeting showed that the bispecific antibody showcased strong 4-1BB agonistic activity and antitumor effects in a PD-L1–dependent fashion as well as 4-1BB–positive/CD8-positive T-cell activation and proliferation.^3,4 Investigators concluded that this may allow the agent to overcome limitations observed with PD-1/PD-L1–targeted therapies and could serve to minimize the risk of peripheral effects.

The phase 1 trial enrolled patients with a histologically and/or cytologically confirmed diagnosis of any progressive locally advanced or metastatic solid tumor that is relapsed/refractory after the last line of therapy received.5 For these patients, standard treatment did not exist, was previously ineffective, or was not determined to be appropriate. Patients needed to have acceptable hematologic, hepatic, and renal function.

Patients could have had adverse effects (AEs), with the exception of alopecia, or grade 2 AEs from previous therapy that were stable or irreversible and had improved to grade 1 or baseline more than 2 weeks before the study drug was initiated.

Patients could not have previously received a monoclonal antibody or investigational agent within 28 days before the study drug was initiated. They also could not have received prior chemotherapy or radiation within 14 days, or targeted small molecule therapy within 5 half-lives, of treatment with TJ-L14B/ABL503.

Other exclusion criteria included requiring or receiving systemic steroid therapy or other immunosuppressive treatments within 2 weeks before the start of the study drug, risk factors for bowel obstruction or perforation, having discontinued a previous immunomodulatory therapy because of intolerability, and prior receipt of an anti–4-1BB antibody.

For the dose-escalation portion of the trial, the bispecific antibody is being administered intravenously on days 1 and 15 of each 28-day treatment cycle. Safety and pharmacokinetic (PK) data from this portion of the research will inform the dosing interval for the dose-expansion portion of the trial.

The primary objectives of the trial include number of dose-limiting toxicities, as well as number of AEs, immune-related AEs, infusion-related reactions, serious AEs, and lab abnormalities. Secondary objectives include evaluating objective response rate, and the PK and immunogenicity of the agent.

In April 2021, it was announced that the first patient on the trial was dosed with TJ-L14B/ABL503.²

“The clinical responses observed in the phase 1 clinical study of TJ-L14B/ABL503, though in early stages, not only provide validation of our technology platform but also offer proof of the mechanism behind this innovative bispecific antibody,” Sang Hoon Lee, chief executive officer of ABL Bio, Inc., added in the press release.¹ “We express our heartfelt gratitude to the patients who participated in the study, healthcare professionals, study investigators, and our partners for their invaluable collaboration in achieving this milestone. Concurrently, we are expediting patent filings for TJ-L14B/ABL503 to safeguard its rights and facilitate its seamless entry into the global market.”

References

1. I-Mab and ABL Bio announce latest updates of PD-L1 and 4-1BB bispecific antibody TJ-L14B/ABL503. News release. I-Mab. October 10, 2023. Accessed October 10, 2023. https://ir.i-mabbiopharma.com/news-releases/news-release-details/i-mab-and-abl-bio-announce-latest-updates-pd-l1-and-4-1bb
2. I-Mab and ABL Bio announce first patient dosed in phase 1 trial of bispecific antibody TJ-L14B/ABL503 in patients with advanced or metastatic solid tumors. News release. I-Mab. April 6, 2021. Accessed October 10, 2023. https://ir.i-mabbiopharma.com/news-releases/news-release-details/i-mab-and-abl-bio-announce-first-patient-dosed-phase-1-trial
3. I-Mab and ABL Bio present preclinical data of TJ-CD4B/ABL111 and TJ-L14B/ABL503 at the 2021 SITC Annual Meeting. News release. I-Mab. October 5, 2021. Accessed October 10, 2023. https://ir.i-mabbiopharma.com/news-releases/news-release-details/i-mab-and-abl-bio-present-preclinical-data-tj-cd4babl111-and-tj
4. Jung U, Jeon J, Lee S, et al. ABL503 (TJ-L14B), PD-L1x4–1BB bispecific antibody induces superior anti-tumor activity by PD-L1-dependent 4–1BB activation with the increase of 4–1BB+CD8+ T cells in tumor microenvironment. Journal for Immunotherapy of Cancer. 2021;9(suppl 2). doi:10.1136/jitc-2021-SITC2021.892
5. This is a study to evaluate the safety and tolerability of ABL503, and to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of ABL503 in subjects with any progressive locally advanced or metastatic solid tumors. ClinicalTrials.gov. Updated August 25, 2023. Accessed October 10, 2023. https://www.clinicaltrials.gov/study/NCT04762641