ABBV-400 for Advanced Solid Cancers

Recruiting at 134 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: AbbVie

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

Compensation: Varies

Number of Visits: Unknown

520 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new drug called ABBV-400 for adults with advanced cancers. The study aims to find the best dose and see how well it works, both alone and with other treatments. Patients will receive the drug through an IV and be closely monitored for effects and side effects.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications. However, since the trial involves investigational drugs, it's possible that some medications might need to be adjusted. Please discuss with the trial team for specific guidance.

What data supports the idea that ABBV-400 for Advanced Solid Cancers is an effective treatment?

The available research does not provide specific data on the effectiveness of ABBV-400 for Advanced Solid Cancers. Instead, it discusses other treatments and therapies for solid tumors, such as monoclonal antibodies and immune checkpoint inhibitors, which have shown promise in treating various cancers. Without direct data on ABBV-400, we cannot conclude its effectiveness compared to these other treatments. ^{1 2 3 4 5}

What safety data is available for ABBV-400 in treating advanced solid cancers?

The provided research does not contain specific safety data for ABBV-400, Telisotuzumab adizutecan, or its other names. The studies focus on immune checkpoint inhibitors like PD-1 and CTLA-4 inhibitors, which are different treatments. Therefore, no relevant safety data for ABBV-400 is available in the given research. ^{6 7 8 9 10}

Is the drug ABBV-400 a promising treatment for advanced solid cancers?

ABBV-400, also known as Telisotuzumab adizutecan, is a promising drug for advanced solid cancers because it is a monoclonal antibody. Monoclonal antibodies have been shown to be effective in treating solid tumors by targeting specific growth factors or receptors on cancer cells, which can help stop the growth of tumors. ^{11 12 13 14 15}

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

This trial is for adults with advanced solid tumors, including non-small cell lung cancer (NSCLC) with or without EGFR mutations, gastroesophageal adenocarcinoma, and colorectal cancer that have progressed after prior treatments. Participants must be in good physical condition (ECOG 0 or 1), have measurable disease, meet specific lab criteria, and not be candidates for surgery or other beneficial therapies.

Inclusion Criteria

My advanced stomach or esophagus cancer has worsened after certain treatments.

I am fully active or can carry out light work.

My advanced colorectal cancer does not have the BRAF V600E mutation and has worsened despite treatment.

Exclusion Criteria

I have a history of lung conditions as specified in the study details.

I have not been treated with TAS-102 or regorafenib.

I have never needed steroids for lung inflammation nor show signs of it on a chest CT.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of ABBV-400 monotherapy to determine the best dose

Varies

Regular visits at approved institutions

Dose Expansion

Participants receive ABBV-400 monotherapy or in combination with bevacizumab to confirm the dose

Varies

Regular visits at approved institutions

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 24 months

Treatment Details

Interventions

• ABBV-400

Trial Overview The study tests ABBV-400's safety and effect on tumor activity in patients with various advanced cancers. It involves a dose escalation phase to find the best dose followed by an expansion phase to confirm it. Patients will receive different doses of ABBV-400 intravenously at multiple global sites.

Participant Groups

Group I: Part 7biii (Combination Comparator) Experimental Treatment 2 Interventions

Participants with CRC will receive trifluridine/tipiracil (TAS-102) in combination with bevacizumab.

Group II: Part 7bii (Combination Dose Optimization High Dose) Experimental Treatment 2 Interventions

Participants with CRC will receive the high dose determined in the dose escalation arm (Part 7a) of ABBV-400 in combination with bevacizumab.

Group III: Part 7bi (Combination Dose Optimization Low Dose) Experimental Treatment 2 Interventions

Participants with CRC will receive the low dose determined in the dose escalation arm (Part 7a) of ABBV-400 in combination with bevacizumab.

Group IV: Part 7a (Combination Dose Escalation) Experimental Treatment 2 Interventions

Participants with CRC will receive escalating doses of ABBV-400 in combination with bevacizumab.

Group V: Part 6 (MET Mutation) Experimental Treatment 1 Intervention

Participants with MET mutation will receive ABBV-400 at the RP2D and various dose levels for dose optimization.

Group VI: Part 5 (MET Amplification) Experimental Treatment 1 Intervention

Participants with mesenchymal-epithelial transition proto-oncogene (MET) amplification will receive ABBV-400 at the RP2D and various dose levels for dose optimization.

Group VII: Part 4 (Colorectal Cancer) Experimental Treatment 1 Intervention

Participants with Colorectal Cancer (CRC) will receive ABBV-400 at the RP2D and various dose levels for dose optimization.

Group VIII: Part 3 (Gastroesophageal Adenocarcinoma/Gastroesophagel Junct Experimental Treatment 1 Intervention

Participants with gastroesophageal adenocarcinoma will receive ABBV-400 at the RP2D.

Group IX: Part 2iii (Squamous NSCLC) Experimental Treatment 1 Intervention

Participants with squamous NSCLC will receive ABBV-400 at RP2D.

Group X: Part 2ii (mutEGFR NSCLC) Experimental Treatment 1 Intervention

Participants with non-Squamous mutEGFR NSCLC will receive ABBV-400 at RP2D.

Group XI: Part 2i (wtEGFR Non-Small Cell Lung Cancer [NSCLC]) Experimental Treatment 1 Intervention

Participants with non-squamous wtEGFR NSCLC will receive ABBV-400 at the Recommended Phase 2 dose (RP2D).

Group XII: Part 1 (Monotherapy Dose Escalation) Experimental Treatment 1 Intervention

Participants with advanced solid tumors will receive escalating doses of ABBV-400.

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

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]

In a phase II study involving 110 patients with advanced clear cell renal cell carcinoma (ccRCC), pembrolizumab demonstrated a 36.4% objective response rate, indicating significant antitumor activity as a first-line treatment.

The treatment was generally well-tolerated, with 30% of patients experiencing grade 3-5 adverse events, primarily colitis and diarrhea, which aligns with safety profiles observed in other cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-Label, Single-Arm Phase II Study of Pembrolizumab Monotherapy as First-Line Therapy in Patients With Advanced Clear Cell Renal Cell Carcinoma. McDermott, DF., Lee, JL., Bjarnason, GA., et al.[2022]

Recent advances in antibody-based therapies, such as trastuzumab and bevacizumab, have shown promise in treating various solid tumors, including breast and colorectal cancers, with acceptable safety profiles.

Combining monoclonal antibodies with small-molecule inhibitors may enhance treatment efficacy and specificity, suggesting a potential direction for future cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent advances relating to the clinical application of naked monoclonal antibodies in solid tumors. Argyriou, AA., Kalofonos, HP.[2021]

The combination of CP-870,893, an agonist CD40 antibody, with gemcitabine was well-tolerated in 22 patients with advanced pancreatic ductal adenocarcinoma, with the maximum-tolerated dose identified at 0.2 mg/kg, although one serious adverse event occurred.

This treatment led to immune activation and showed antitumor activity, with four patients achieving a partial response and significant decreases in FDG uptake in primary pancreatic lesions, suggesting potential therapeutic benefits that warrant further investigation in Phase II studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of an agonist CD40 monoclonal antibody (CP-870,893) in combination with gemcitabine in patients with advanced pancreatic ductal adenocarcinoma. Beatty, GL., Torigian, DA., Chiorean, EG., et al.[2022]

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]

Targeting CTLA-4 with antibodies has shown significant benefits in treating solid tumors and blood cancers, especially when used in combination with anti-PD-1 antibodies, enhancing antitumor immune responses.

While the combination therapy can lead to a higher incidence of autoimmune-like adverse events, these side effects are often linked to improved treatment responses, and can be managed effectively with prompt recognition and immunosuppressive treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting CTLA-4 in cancer: Is it the ideal companion for PD-1 blockade immunotherapy combinations? De Silva, P., Aiello, M., Gu-Trantien, C., et al.[2021]

Tislelizumab, a PD-1 inhibitor, significantly improved the overall response rate (ORR) and disease control rate (DCR) in patients with malignant solid tumors, with odds ratios of 2.59 and 1.78, respectively, based on a meta-analysis of seven phase III trials involving 3478 participants.

The treatment also demonstrated improved overall survival (OS) and progression-free survival (PFS), with hazard ratios of 0.71 and 0.68, indicating that tislelizumab is an effective option for patients with solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tislelizumab for malignant solid tumor: a systematic review and meta-analysis of phase III randomized trials. Abushanab, AK., Mustafa, MT., Mousa, MT., et al.[2023]

A retrospective analysis of adverse events related to PD-1/PD-L1 inhibitors revealed a significant association between Pembrolizumab and hepatitis B reactivation (HBVr), with a reporting odds ratio of 2.32, indicating a higher risk compared to other treatments.

No cases of HBVr were reported with Ipilimumab or Avelumab, suggesting that not all immune checkpoint inhibitors carry the same risk, highlighting the need for further prospective studies to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatitis B Virus Reactivation in Cancer Patients Treated With Immune Checkpoint Inhibitors. Burns, EA., Muhsen, IN., Anand, K., et al.[2023]

In a study of 45 patients with metastatic melanoma treated with the combination of nivolumab and ipilimumab, the disease control rate was 54% and the objective response rate was 29%, indicating moderate efficacy in a real-world setting.

The treatment had a high toxicity profile, with 88% of patients experiencing adverse events, and 44% discontinuing treatment due to these events, highlighting the need for careful monitoring and management of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world efficacy and toxicity of combined nivolumab and ipilimumab in patients with metastatic melanoma. Parakh, S., Randhawa, M., Nguyen, B., et al.[2019]

CTLA-4 inhibitor monotherapy shows a clear dose-dependent relationship with various adverse events (AEs), unlike PD-1 inhibitor monotherapy, indicating that higher doses may lead to more side effects.

When PD-1 inhibitors are used in combination with CTLA-4 inhibitors, the rates of treatment-related and immune-mediated AEs become even more dependent on the dose of the CTLA-4 inhibitor, suggesting careful monitoring is needed in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose dependence of treatment-related adverse events for immune checkpoint inhibitor therapies: a model-based meta-analysis. Shulgin, B., Kosinsky, Y., Omelchenko, A., et al.[2021]

Trastuzumab, the first monoclonal antibody approved for metastatic breast cancer, is currently being evaluated in large-scale phase III trials for its effectiveness in combination with chemotherapy and as a maintenance therapy.

The newly developed CH401 antibody shows promising results, completely suppressing tumor growth in mice and inducing more apoptosis in HER2-overexpressing gastric cancer cells compared to trastuzumab, highlighting its potential as a more effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monoclonal antibodies as effective therapeutic agents for solid tumors. Hinoda, Y., Sasaki, S., Ishida, T., et al.[2020]

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 combination of isatuximab and atezolizumab (Isa + Atezo) demonstrated an acceptable safety profile in a study of 107 patients with various solid tumors, with no dose-limiting toxicities observed and most treatment-emergent adverse events being manageable.

Despite effectively reducing CD38+ immune cells in the tumor microenvironment, the treatment did not significantly enhance the effectiveness of PD-L1 blockade, indicating that CD38 inhibition alone may not improve responses to immunotherapy in these solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab plus atezolizumab in patients with advanced solid tumors: results from a phase I/II, open-label, multicenter study. Simonelli, M., Garralda, E., Eskens, F., et al.[2022]

Volociximab is a chimeric monoclonal antibody designed to inhibit angiogenesis by targeting AAB1, a protein involved in the alpha5/beta1 integrin, which is crucial for tumor blood vessel formation.

Currently, two phase II clinical trials are assessing the efficacy of volociximab in treating solid tumors, including renal cell carcinoma, and it is also being explored for age-related macular degeneration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug evaluation: Volociximab, an angiogenesis-inhibiting chimeric monoclonal antibody. Kuwada, SK.[2017]

The phase I/II trial of GEN1042, a bispecific antibody targeting CD40 and 4-1BB, indicates that the drug is well tolerated by patients with advanced solid tumors.

Preliminary results suggest that GEN1042 shows activity against these tumors, highlighting its potential as a new treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual-Targeting Approach for CD40 and 4-1BB. [2022]

References

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

MEDI5752 Suppresses Two Immune Checkpoints. [2022]

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

Open-Label, Single-Arm Phase II Study of Pembrolizumab Monotherapy as First-Line Therapy in Patients With Advanced Clear Cell Renal Cell Carcinoma. [2022]

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

Recent advances relating to the clinical application of naked monoclonal antibodies in solid tumors. [2021]

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

A phase I study of an agonist CD40 monoclonal antibody (CP-870,893) in combination with gemcitabine in patients with advanced pancreatic ductal adenocarcinoma. [2022]

5. 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]

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

Targeting CTLA-4 in cancer: Is it the ideal companion for PD-1 blockade immunotherapy combinations? [2021]

7. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tislelizumab for malignant solid tumor: a systematic review and meta-analysis of phase III randomized trials. [2023]

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

Hepatitis B Virus Reactivation in Cancer Patients Treated With Immune Checkpoint Inhibitors. [2023]

9. Australia pubmed.ncbi.nlm.nih.gov

Real-world efficacy and toxicity of combined nivolumab and ipilimumab in patients with metastatic melanoma. [2019]

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

Dose dependence of treatment-related adverse events for immune checkpoint inhibitor therapies: a model-based meta-analysis. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Monoclonal antibodies as effective therapeutic agents for solid tumors. [2020]

12. 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]

13. England pubmed.ncbi.nlm.nih.gov

Isatuximab plus atezolizumab in patients with advanced solid tumors: results from a phase I/II, open-label, multicenter study. [2022]

14. England pubmed.ncbi.nlm.nih.gov

Drug evaluation: Volociximab, an angiogenesis-inhibiting chimeric monoclonal antibody. [2017]

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

Dual-Targeting Approach for CD40 and 4-1BB. [2022]