ABBV-400 for Advanced Cancer

Recruiting at 61 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: AbbVie

Must not be taking: Chemotherapy, Immunotherapy, Biologics, others

Disqualifiers: Interstitial lung disease, Untreated brain metastases, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 104 weeks

260 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop any anticancer therapy, including chemotherapy, radiation, or immunotherapy, at least 28 days before starting ABBV-400. However, palliative radiation for certain conditions is allowed without a waiting period. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

What makes the drug ABBV-400 unique for treating advanced cancer?

ABBV-400, also known as Telisotuzumab adizutecan, is unique because it is a targeted therapy designed to specifically attack cancer cells with less impact on healthy cells, potentially reducing side effects compared to traditional chemotherapy. ^{1 2 3 4 5}

What is the purpose of this trial?

This trial tests ABBV-400, a new drug, on adults with difficult-to-treat cancers. The goal is to see how safe it is and how well it works. Patients will be monitored frequently.

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

Adults with certain advanced solid tumors like liver, pancreatic, biliary tract cancers, esophageal squamous cell carcinoma, triple negative breast cancer, hormone receptor+/HER2- breast cancer or head and neck squamous-cell-carcinoma. Participants must have measurable disease activity and meet specific laboratory criteria without active lung issues or recent other cancer treatments.

Inclusion Criteria

I have an autoimmune or inflammatory condition affecting my lungs, or I've had a lung removed.

You have a measurable tumor according to specific guidelines.

Your test results meet the specific requirements outlined in the study's plan.

Exclusion Criteria

I have brain metastases but don't need steroids for swelling and have been stable for 2 weeks after treatment.

I have no active cancer other than what is allowed in the study.

I have no ongoing side effects from cancer treatment above mild, except for hair loss.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravenous (IV) ABBV-400 monotherapy for up to 2 years

Up to 104 weeks

Regular visits at approved institutions

Safety Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 104 weeks

Treatment Details

Interventions

• ABBV-400

Trial Overview The trial is testing ABBV-400 as a monotherapy for up to two years in adults with various advanced solid tumors. Patients are grouped based on their type of cancer and will receive regular medical assessments including blood tests and questionnaires to monitor the treatment's effect.

Participant Groups

Group I: Cohort 8: PROC/Primary Peritoneal/Fallopian Tube Cancer Experimental Treatment 1 Intervention

Participants with Platinum Resistant High Grade Epithelial Ovarian Cancer (PROC)/primary peritoneal/fallopian tube cancer will receive ABBV-400 for up to 2 years during and up to the treatment period with an additional safety follow-up period of up to 2 years.

Group II: Cohort 7: Head and Neck Squamous-cell-carcinoma (HNSCC) Experimental Treatment 1 Intervention

Participants with HNSCC will receive ABBV-400 for up to 2 years during and up to the treatment period with an additional safety follow-up period of up to 2 years.

Group III: Cohort 6: Hormone Receptor+/HER2-breast Cancer (HR+/HER2-BC) Experimental Treatment 1 Intervention

Participants with HR+/HER2-BC will receive ABBV-400 for up to 2 years during and up to the treatment period with an additional safety follow-up period of up to 2 years.

Group IV: Cohort 5: Triple Negative Breast Cancer (TNBC) Experimental Treatment 1 Intervention

Participants with TNBC will receive ABBV-400 for up to 2 years during and up to the treatment period with an additional safety follow-up period of up to 2 years.

Group V: Cohort 4: Esophageal Squamous Cell Carcinoma, (ESCC) Experimental Treatment 1 Intervention

Participants with ESCC will receive ABBV-400 for up to 2 years during and up to the treatment period with an additional safety follow-up period of up to 2 years.

Group VI: Cohort 3: Biliary Tract Cancers (BTC) Experimental Treatment 1 Intervention

Participants with BTC will receive ABBV-400 for up to 2 years during and up to the treatment period with an additional safety follow-up period of up to 2 years.

Group VII: Cohort 2: Pancreatic Ductal Adenocarcinoma (PDAC) Experimental Treatment 1 Intervention

Participants with PDAC will receive ABBV-400 for up to 2 years during and up to the treatment period with an additional safety follow-up period of up to 2 years.

Group VIII: Cohort 1: Hepatocellular Carcinoma (HCC) Experimental Treatment 1 Intervention

Participants with HCC will receive ABBV-400 for up to 2 years during and up to the treatment period with an additional safety follow-up period of up to 2 years.

Who Is Running the Clinical Trial?

AbbVie

Lead Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Findings from Research

ABBV-428, a tumor-targeted bispecific antibody, demonstrated an acceptable safety profile in a phase I study with 59 patients, showing no maximum tolerated dose reached and only mild infusion-related reactions reported.

Despite its safety, ABBV-428 showed minimal clinical activity in treating advanced mesothelioma and ovarian cancer, with only 36% of patients achieving stable disease, indicating that while the drug is safe, its effectiveness may need further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of ABBV-428, a mesothelin-CD40 bispecific, in patients with advanced solid tumors. Luke, JJ., Barlesi, F., Chung, K., et al.[2023]

In a Phase I clinical trial involving 23 patients with advanced solid tumors, the intratumoral administration of the CD40 agonistic antibody ADC-1013 was found to be well tolerated, with most adverse events being mild and transient.

The treatment led to significant pharmacodynamic effects, including a marked decrease in peripheral blood B cell levels and increased activation of T cells, suggesting that ADC-1013 effectively activates the immune response against tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-human study with intratumoral administration of a CD40 agonistic antibody, ADC-1013, in advanced solid malignancies. Irenaeus, SMM., Nielsen, D., Ellmark, P., et al.[2020]

DuoBody-CD40×4-1BB is a novel bispecific antibody that effectively enhances antitumor immunity by conditionally stimulating CD40 and 4-1BB, leading to improved dendritic cell maturation and T-cell activation in both laboratory assays and in patients with advanced solid tumors.

In a first-in-human clinical trial, DuoBody-CD40×4-1BB demonstrated significant immune modulation in patients, suggesting its potential as an effective treatment strategy for cancer when combined with PD-1 blocking antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DuoBody-CD40x4-1BB induces dendritic-cell maturation and enhances T-cell activation through conditional CD40 and 4-1BB agonist activity. Muik, A., Adams 3rd, HC., Gieseke, F., et al.[2022]

XFab-α4-1BB/CD40L is a bispecific antibody that effectively activates dendritic cells and promotes the proliferation of tumor-reactive T cells, leading to significant tumor regression in mouse models.

In non-human primates, XFab-α4-1BB/CD40L demonstrated a favorable safety profile with no liver toxicity observed at doses up to 51 mg/kg, indicating its potential for safe use in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

XFab-α4-1BB/CD40L fusion protein activates dendritic cells, improves expansion of antigen-specific T cells, and exhibits antitumour efficacy in multiple solid tumour models. Wang, B., Liu, Y., Yuan, R., et al.[2023]

The study developed bispecific antibodies that combine anti-CD40 and anti-41BB antibodies with a PDL1-specific blocking domain, allowing for effective immune stimulation without relying on FcγR binding, which can cause unwanted side effects.

These bispecific antibodies maintained their binding properties and effectively activated CD40 and 41BB signaling while also inhibiting PD1 activation, suggesting a promising strategy for enhancing the efficacy of cancer immunotherapy by linking checkpoint blockade with immune activation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD40- and 41BB-specific antibody fusion proteins with PDL1 blockade-restricted agonism. Medler, J., Kucka, K., Melo, V., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Phase I study of ABBV-428, a mesothelin-CD40 bispecific, in patients with advanced solid tumors. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

First-in-human study with intratumoral administration of a CD40 agonistic antibody, ADC-1013, in advanced solid malignancies. [2020]

3. England pubmed.ncbi.nlm.nih.gov

DuoBody-CD40x4-1BB induces dendritic-cell maturation and enhances T-cell activation through conditional CD40 and 4-1BB agonist activity. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

XFab-α4-1BB/CD40L fusion protein activates dendritic cells, improves expansion of antigen-specific T cells, and exhibits antitumour efficacy in multiple solid tumour models. [2023]

5. Australia pubmed.ncbi.nlm.nih.gov

CD40- and 41BB-specific antibody fusion proteins with PDL1 blockade-restricted agonism. [2022]