ABL503 for Solid Cancers

Recruiting at 11 trial locations

Overseen By Juyeun Jeon

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: ABL Bio, Inc.

Must not be taking: Monoclonal antibodies, Steroids

Disqualifiers: Bowel obstruction, Pneumonitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ABL503 (also known as TJ-L14B or Ragistomig) for individuals with advanced solid tumors that no longer respond to other treatments. This first-time study aims to assess the safety and effectiveness of ABL503 and determine the optimal dose. Participants will receive the treatment every two weeks, with researchers adjusting the dose based on safety and other factors. Individuals with solid tumors unresponsive to their last treatment and lacking other standard options might be suitable for this trial. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting. You must not have had any anticancer monoclonal antibody treatment or investigational therapy within 28 days, chemotherapy or radiation therapy within 2 weeks, or targeted small molecule therapy within 5 half-lives before starting the study drug. Additionally, you should not be on systemic steroid therapy or any other immunosuppressive therapy within 14 days prior to the study drug administration.

Is there any evidence suggesting that ABL503 is likely to be safe for humans?

Research has shown that ABL503 is generally safe for patients. An earlier study found that ABL503 helped shrink tumors in 6 out of 39 patients and was well-tolerated, causing no severe side effects for most participants. In lab tests, ABL503 also appeared safer than other treatments. As this is the first human trial of ABL503, it is in a Phase 1 trial, indicating that more research is needed to fully understand its safety. Overall, early results suggest ABL503 is safe for patients, but ongoing studies will provide more information. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

ABL503 is unique because it targets solid cancers using a bispecific antibody approach, which is different from the standard chemotherapy or single-targeted therapies. This treatment stands out by simultaneously engaging two different targets, potentially enhancing its effectiveness and specificity against cancer cells. Researchers are excited about ABL503 because it holds the promise of more precise cancer targeting, potentially leading to fewer side effects and improved outcomes compared to existing treatments.

What evidence suggests that ABL503 might be an effective treatment for solid cancers?

Research has shown that ABL503, the investigational treatment in this trial, has promising early results for treating solid tumors. In studies, 6 out of 39 patients with advanced or spreading solid tumors experienced positive responses, with their tumors either shrinking or stopping growth. ABL503 is a special type of antibody that targets two proteins, PD-L1 and 4-1BB, to help the immune system fight cancer cells. Animal studies demonstrated that when combined with another treatment, Pembrolizumab, ABL503 further reduced tumor growth. These findings suggest that ABL503 might benefit people with difficult-to-treat solid cancers. ^{1 4 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that have worsened after treatment or don't respond to standard therapies. Participants must have recovered from major side effects of previous treatments, except hair loss and certain stable conditions, and should have good blood, liver, and kidney function.

Inclusion Criteria

My side effects from previous treatments, except for hair loss or stable nerve damage, have mostly gone away.

My blood, liver, and kidney tests are all within normal ranges.

My cancer has returned or didn't respond to treatment and cannot be surgically removed.

Exclusion Criteria

I haven't had cancer antibody treatment or experimental therapy in the last 28 days.

I stopped previous immune therapy due to severe side effects needing steroids.

I haven't taken steroids or immunosuppressants in the last 14 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive ABL503 biweekly in a 28-day cycle to determine the maximum tolerated dose and recommended phase 2 dose

Up to 12 months

Biweekly visits

Dose Expansion

Participants receive ABL503 at the determined dose to further evaluate safety and preliminary antitumor activity

Up to 12 months

Biweekly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ABL503

Trial Overview ABL503 is being tested in this Phase 1 trial to find the safest dose for future studies. The study has three parts: finding the maximum tolerated dose (MTD), expanding the dose range (RP2D), and testing on specific tumor types.

How Is the Trial Designed?

Group I: ABL503 Experimental Treatment 1 Intervention

ABL503 will be administered biweekly of every 28-day cycle in the dose-escalation. The dosing interval to be used in the dose-expansion part will be re-evaluated based on the emerging safety and PK data from the dose-escalation part of the study.

Who Is Running the Clinical Trial?

ABL Bio, Inc.

Lead Sponsor

Trials

6

Recruited

390+

Published Research Related to This Trial

ABL501, a bispecific antibody targeting both LAG-3 and PD-L1, enhances T cell activation more effectively than using single antibodies, leading to improved immune responses against tumors.

In preclinical models, ABL501 demonstrated strong antitumor efficacy and is currently being evaluated in a first-in-human clinical trial, indicating its potential as a novel cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LAG-3xPD-L1 bispecific antibody potentiates antitumor responses of T cells through dendritic cell activation. Sung, E., Ko, M., Won, JY., et al.[2023]

In triple negative breast cancer (TNBC), which is particularly aggressive and has no targeted treatments, the protein geminin is overexpressed in about 50% of tumors, and its activity is regulated by the tyrosine kinase c-Abl, which is found in the nucleus of geminin-overexpressing tumors.

Inhibiting c-Abl with drugs like imatinib or nilotinib not only inactivates geminin but also converts it from promoting cancer to inducing cell death, showing promise as a novel treatment for aggressive breast cancers that overexpress geminin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Geminin overexpression promotes imatinib sensitive breast cancer: a novel treatment approach for aggressive breast cancers, including a subset of triple negative. Blanchard, Z., Mullins, N., Ellipeddi, P., et al.[2022]

ABL family kinases, while primarily known for their role in leukemia, are also implicated in various solid tumors where they promote processes like tumor growth, invasion, and metastasis through unique signaling pathways.

Targeting ABL kinases could potentially reduce tumor growth and prevent metastasis, but their dual role as both promoters and potential suppressors of tumors in different contexts highlights the need for careful consideration in treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EnABLing Tumor Growth and Progression: Recent progress in unraveling the functions of ABL kinases in solid tumor cells. Tripathi, R., Liu, Z., Plattner, R.[2022]

The ABL tyrosine kinases, particularly ABL1 and ABL2, are implicated in the progression of various solid tumors, in addition to their established role in leukemia, based on findings from mouse models and genomic studies.

Preclinical studies indicate that small molecule inhibitors targeting ABL kinases may provide therapeutic benefits for certain solid tumors, suggesting a potential new treatment avenue for these cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Emerging Role of ABL Kinases in Solid Tumors. Wang, J., Pendergast, AM.[2022]

AP24534 is a new, potent oral multitargeted kinase inhibitor that effectively targets the BCR-ABL(T315I) mutation and other resistant BCR-ABL mutants in chronic myeloid leukemia (CML).

In preclinical studies, AP24534 not only inhibited tumor growth driven by the BCR-ABL(T315I) mutation in mice but also completely overcame resistance in laboratory tests, suggesting strong potential for clinical use in CML treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. O'Hare, T., Shakespeare, WC., Zhu, X., et al.[2023]

In a pilot study involving 13 patients with advanced melanoma, breast cancer, and colon cancer, the drug PD-0325901 showed significant tolerability issues, particularly at doses of 15 mg twice daily or higher, leading to early termination of the study due to adverse effects like gait disturbance and memory impairment.

Despite the safety concerns, one patient achieved a complete response and five had stable disease, suggesting that PD-0325901 may have preliminary antitumor activity, warranting further investigation at lower doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot study of PD-0325901 in previously treated patients with advanced melanoma, breast cancer, and colon cancer. Boasberg, PD., Redfern, CH., Daniels, GA., et al.[2021]

The phase I trial of MEDI5752, a bispecific antibody that targets both PD-1 and CTLA4, shows that the drug is well tolerated by patients.

Preliminary results indicate that MEDI5752 is active in treating various tumor types, with durable responses observed, suggesting potential effectiveness in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MEDI5752 Suppresses Two Immune Checkpoints. [2022]

The combination of afatinib (40 mg QD) and vinorelbine (25 mg/m² weekly) was found to be tolerable in Japanese patients with advanced solid tumors, with dose modifications for adverse events allowing for better management of side effects.

Two patients experienced partial tumor responses, and eight had stable disease, indicating preliminary efficacy of this treatment regimen, which is recommended for further phase II/III trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of afatinib plus vinorelbine in Japanese patients with advanced solid tumors, including breast cancer. Mukai, H., Masuda, N., Ishiguro, H., et al.[2018]

The maximum tolerated dose (MTD) of afatinib combined with paclitaxel was determined to be 40mg of afatinib with 80mg/m² of paclitaxel, showing manageable adverse effects such as diarrhea and fatigue in a study of 16 patients.

The combination treatment demonstrated promising antitumor activity, with 31% of patients achieving confirmed partial responses, particularly in non-small cell lung cancer, and half of the patients remaining on the study for at least 6 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of daily afatinib, an irreversible ErbB family blocker, in combination with weekly paclitaxel in patients with advanced solid tumours. Suder, A., Ang, JE., Kyle, F., et al.[2018]

In a meta-analysis of five studies involving 435 patients with stage IV EGFR-mutated non-small cell lung cancer, PD-L1-positive tumors were linked to significantly worse progression-free survival (PFS) outcomes compared to PD-L1-negative tumors, indicating that PD-L1 expression may negatively impact treatment effectiveness.

The analysis revealed that the negative impact of PD-L1 expression on PFS was more pronounced with older-generation EGFR tyrosine kinase inhibitors (TKIs) compared to third-generation TKIs, suggesting that the choice of treatment may influence outcomes based on PD-L1 status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of programmed death-ligand 1 expression on the patients of stage IV non-small cell lung cancer harboring epidermal growth factor receptor mutation: a systematic review and meta-analysis. Lee, CC., Soon, YY., Leong, CN., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2529

Phase 1 trial safety and efficacy of ragistomig, a bispecific ... Conclusions: ABL503 had a manageable safety profile and demonstrated promising anti-tumor activity, with objective responses in 6 out of 39 ...

2. onclive.com onclive.com/view/tj-l14b-abl503-showcases-early-efficacy-signals-in-advanced-or-metastatic-solid-tumors

TJ-L14B/ABL503 Showcases Early Efficacy Signals in ... TJ-L14B/ABL503 demonstrated preliminary efficacy signals in the form of responses in patients with progressive, locally advanced or metastatic solid tumors.

3. ascopubs.org ascopubs.org/doi/pdf/10.1200/JCO.2024.42.16_suppl.2529

Phase 1 trial safety and efficacy of ragistomig, a bispecific ... Conclusions: ABL503 had a manageable safety profile and demonstrated promising anti-tumor activity, with objective responses in 6 out of 39 efficacy-evaluable ...

4. jitc.bmj.com jitc.bmj.com/content/11/Suppl_1/A943

845 ABL503 (TJ-L14B), PD-L1×4–1BB bispecific antibody, ... Consistently, the combination of ABL503 (TJ-L14B) with Pembrolizumab synergistically alleviated tumor growth in the mouse model, with enhanced ...

5. jitc.bmj.com jitc.bmj.com/content/9/Suppl_2/A935

892 ABL503 (TJ-L14B), PD-L1x4–1BB bispecific antibody ... Our data indicate that PD-L1 and 4-1BB dual targeting bispecific antibody, ABL503 (TJ-L14B), shows potent 4-1BB agonistic activity and anti-tumor effect.

6. imab.gcs-web.com imab.gcs-web.com/news-releases/news-release-details/abl-bio-announces-publication-preclinical-data-demonstrating

ABL Bio Announces Publication of Preclinical Data ... - I-MAB ABL503/TJ-L14B demonstrates stronger anti-tumor efficacy than anti-PD-L1 or anti-4-1BB monotherapy as well as a good safety profile

7. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04762641/

Clinical Trial: NCT04762641 This is a Study to Evaluate the Safety and Tolerability of ABL503, and to Determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 ...