ABBV-400 for Advanced Cancer
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: AbbVie
No Placebo Group
Trial Summary
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.
Is the drug ABBV-400 a promising treatment for advanced cancer?Yes, ABBV-400 is a promising treatment for advanced cancer because it is designed to target tumors specifically, which can help activate the body's immune system to fight cancer cells more effectively while minimizing side effects.39111315
What safety data is available for ABBV-400 (Telisotuzumab adizutecan)?The provided research does not contain any safety data for ABBV-400 (Telisotuzumab adizutecan) or its other names. The articles focus on the safety of other cancer treatments, such as nivolumab, atezolizumab, and various biologics, but do not mention ABBV-400 or its related names.5681214
What data supports the idea that ABBV-400 for Advanced Cancer is an effective treatment?The available research does not provide specific data on the effectiveness of ABBV-400 for Advanced Cancer. Instead, it discusses other treatments like sacituzumab govitecan and atezolizumab for similar conditions. Sacituzumab govitecan is shown to help patients with advanced triple-negative breast cancer by prolonging the time before the cancer worsens, and it has fewer side effects compared to another drug, irinotecan. Atezolizumab, when combined with nab-paclitaxel, also shows benefits in prolonging the time before cancer worsens in patients with triple-negative breast cancer. However, there is no direct comparison or data available for ABBV-400 in the provided information.124710
Do I have to stop taking my current medications for the trial?The trial protocol does not specify if you must stop taking your current medications. However, you cannot have received anticancer therapy, including chemotherapy, radiation, immunotherapy, biologic, or investigational therapy, within 28 days or 5 half-lives of the drug (whichever is shorter) before starting ABBV-400. Palliative radiation therapy for bone, skin, or subcutaneous metastases with 10 fractions or less is allowed without a washout period.
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.
I have been diagnosed with a specific type of advanced cancer.
Exclusion Criteria
I have no ongoing side effects from cancer treatment above mild, except for hair loss.
I have a history of serious lung problems.
Treatment Details
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.
8Treatment groups
Experimental Treatment
Group I: Cohort 8: PROC/Primary Peritoneal/Fallopian Tube CancerExperimental Treatment1 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 Treatment1 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 Treatment1 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 Treatment1 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 Treatment1 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 Treatment1 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 Treatment1 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 Treatment1 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.
Find a clinic near you
Research locations nearbySelect from list below to view details:
South Texas Accelerated Research Therapeutics/ ID# 260404San Antonio, TX
Lifespan Cancer Institute at Rhode Island Hospital /ID# 257693Providence, RI
Prisma Health Cancer Institute-Faris Road /ID# 257697Greenville, SC
Northwestern University Feinberg School of Medicine /ID# 257378Chicago, IL
More Trial Locations
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Who is running the clinical trial?
AbbVieLead Sponsor
References
An ADC for Triple-Negative Breast Cancer. [2018]A phase II study indicates that sacituzumab govitecan (IMMU-132), a Trop-2-specific antibody linked to the irinotecan metabolite SN-38, prolongs the progression-free survival of patients with advanced triple-negative breast cancer. IMMU-132 is well tolerated, causing fewer and more manageable side effects than irinotecan.
Selective and Concentrated Accretion of SN-38 with a CEACAM5-Targeting Antibody-Drug Conjugate (ADC), Labetuzumab Govitecan (IMMU-130). [2020]Labetuzumab govitecan (IMMU-130), an antibody-drug conjugate (ADC) with an average of 7.6 SN-38/IgG, was evaluated for its potential to enhance delivery of SN-38 to human colonic tumor xenografts. Mice bearing LS174T or GW-39 human colonic tumor xenografts were injected with irinotecan or IMMU-130 (SN-38 equivalents ∼500 or ∼16 μg, respectively). Serum and homogenates of tumors, liver, and small intestine were extracted, and SN-38, SN-38G (glucuronidated SN-38), and irinotecan concentrations determined by reversed-phase HPLC. Irinotecan cleared quickly from serum, with only 1% to 2% injected dose/mL after 5 minutes; overall, approximately 20% was converted to SN-38 and SN-38G. At 1 hour with IMMU-130, 45% to 63% injected dose/mL of the SN-38 was in the serum, with >90% bound to the ADC over 3 days, and with low levels of SN-38G. Total SN-38 levels decreased more quickly than the IgG, confirming a gradual SN-38 release from the ADC. AUC analysis found that SN-38 levels were approximately 11- and 16-fold higher in LS174T and GW-39 tumors, respectively, in IMMU-130-treated animals. This delivery advantage is amplified >30-fold when normalized to SN-38 equivalents injected for each product. Levels of SN-38 and SN-38G were appreciably lower in the liver and small intestinal contents in animals given IMMU-130. On the basis of the SN-38 equivalents administered, IMMU-130 potentially delivers >300-fold more SN-38 to CEA-producing tumors compared with irinotecan, while also reducing levels of SN-38 and SN-38G in normal tissues. These observations are consistent with preclinical and clinical data showing efficacy and improved safety. Mol Cancer Ther; 17(1); 196-203. ©2017 AACR.
First-in-human study with intratumoral administration of a CD40 agonistic antibody, ADC-1013, in advanced solid malignancies. [2020]Agonistic CD40 antibodies activate dendritic cells and can expand and activate tumor-specific T cells. Our purpose was to assess the CD40 agonistic antibody ADC-1013 in the clinical setting including intratumoral administration since preclinical studies have indicated that intratumoral is better than intravenous administration. A Phase I, open label, multicenter study was conducted in patients with advanced solid tumors who had received established treatments. A modified 3 + 3 dose-escalation was applied (every other week dosing). Twenty-three patients were treated with ADC-1013 intratumorally (dosing from 22.5 μg/kg up to 400 μg/kg) or intravenously (dosing at 75 μg/kg). The pharmacodynamic effects observed in the patients were further verified in an hCD40tg mouse model. Adverse events were mostly Common Terminology Criteria for Adverse Events (CTCAE) Grades 1 or 2 and transient. The serum concentration ADC-1013 and cytokine release (MCP-1, TNFα and IL-6) were more pronounced in patients receiving injections in deep metastases compared to patients receiving injections in superficial metastases. Treatment with ADC-1013 resulted in a marked decrease in B cell levels in peripheral blood after 24 h while remaining B cells significantly increased their expression of the cell surface activation marker CD86. Activation of antigen-presenting cells and subsequent activation of T cells were demonstrated in hCD40tg mice. Moreover, ADC-1013 treatment in this mouse model acted synergistically with a PD-1 inhibitor. The results from the first-in-human study of ADC-1013 indicate that intratumoral administration of ADC-1013 into superficial lesions is well tolerated at clinically relevant doses and associated with pharmacodynamic responses.
Subgroup analysis of Japanese patients in a Phase 3 study of atezolizumab in advanced triple-negative breast cancer (IMpassion130). [2023]In the randomised Phase 3 IMpassion130 trial, atezolizumab combined with nab-paclitaxel (atezo + nab-P) in 902 patients with triple-negative breast cancer (TNBC) showed prolonged progression-free survival (PFS) in both the intention-to-treat (ITT) population and programmed death-ligand 1 (PD-L1)-positive subgroup compared with placebo plus nab-P (plac + nab-P). This study assessed the efficacy and safety of atezo + nab-P in the IMpassion130 Japanese subpopulation.
Population pharmacokinetics, exposure-safety, and immunogenicity of atezolizumab in pediatric and young adult patients with cancer. [2023]The iMATRIX-atezolizumab study was a phase I/II, multicenter, open-label study designed to assess the safety and pharmacokinetics of atezolizumab in pediatric and young adult patients. We describe the pharmacokinetics (PK), exposure-safety, and immunogenicity of atezolizumab in pediatric and young adults with metastatic solid tumors or hematologic malignancies enrolled in this study.
An update on the safety of nivolumab for the treatment of advanced melanoma. [2021]Introduction: Due to its unique mechanism of action as an immune checkpoint inhibitor, nivolumab has high antitumor activity, but at the same time this mechanism is responsible for immune-related adverse events that may limit patients' safety and therapy continuation.Areas covered: Long-term safety of nivolumab including 5-year follow-up, safety of nivolumab treatment after ipilimumab therapy, safety of nivolumab in challenging subgroups (elderly, patients with brain metastases, patients with autoimmune disorders), safety of nivolumab in with rare melanoma subtypes (including mucosal melanoma), as well as specificity of AEs reported for nivolumab treatment in melanoma patients in comparison to other cancer types and other immunotherapy molecules, and impact of AEs on response rates and PFS on nivolumab treatment are discussed.Expert opinion: Search for biomarkers that would help us to identify patient populations that may suffer from severe nivolumab toxicity could help in selecting patients that should not be treated with this type of therapy. Novel combinations and immunotherapy drugs including use of NKTR-214 (IL-2 pathway), lymphocyte-activation gene 3 (LAG-3), local injections of talimogene laherparepvec (T-VEC), or systemic use of T-cell receptors agonists such as OX40, CD137, ICOS-1, could provide regimens with limited toxicity and higher activity.
Atezolizumab-induced hemolytic anemia - A case report. [2021]Atezolizumab is currently the only immunotherapy used in conjunction with nab-paclitaxel for locally advanced or triple negative breast cancer. Limited data is available regarding hemolytic anemia as a side effect of atezolizumab.
Hepatitis B Virus Reactivation in Cancer Patients Treated With Immune Checkpoint Inhibitors. [2023]There have been unique adverse events reported with targeted blockade of programmed death-1 (PD-1), programmed death-ligand-1 (PD-L1), and cytotoxic T-lymphocyte-associated protein-4 (CTLA4), including immune mediated toxicities. Recently, there have been reports of hepatitis B reactivation (HBVr) occurring with PD-1/PD-L1 inhibitors, which may result in treatment delays, interruptions, or discontinuation. This retrospective literature review and analysis of the Food and Drug Administration's (FDA) Adverse Events Reporting System (FAERS) queried reported cases of "Hepatitis B reactivation" reported with the PD-1/PD-L1 inhibitors "Pembrolizumab," "Atezolizumab," "Nivolumab," "Durvalumab," "Avelumab," and "Ipilimumab" from initial FDA approval to June 30, 2020. Disproportionality signal analysis was determined by calculating a reporting odds ratio (ROR) and 95% confidence intervals (CI). The ROR was considered significant when the lower and upper limits of the 95% CI were >1 and confirmed by the Fisher exact test (P
Phase I study of ABBV-428, a mesothelin-CD40 bispecific, in patients with advanced solid tumors. [2023]CD40 agonist immunotherapy can potentially license antigen-presenting cells to promote antitumor T-cell activation and re-educate macrophages to destroy tumor stroma. Systemic administration of CD40 agonists has historically been associated with considerable toxicity, providing the rationale for development of tumor-targeted immunomodulators to improve clinical safety and efficacy. This phase I study assessed the safety, tolerability, preliminary antitumor activity, and preliminary biomarkers of ABBV-428, a first-in-class, mesothelin-targeted, bispecific antibody designed for tumor microenvironment-dependent CD40 activation with limited systemic toxicity.
Cost-effectiveness Analysis of Atezolizumab Plus Nab-Paclitaxel for Advanced PD-L1 Positive Triple-Negative Breast Cancer in Japan. [2021]Atezolizumab is an anti-programmed death ligand 1 (PD-L1) antibody that shows good safety and efficacy for patients with PD-L1-positive triple-negative breast cancer (TNBC). The cost of atezolizumab therapy is expensive, and its economic burden is an important problem. In this study, we evaluated the cost effectiveness of atezolizumab plus nab-paclitaxel therapy (AnP) compared with nab-paclitaxel monotherapy (nP) for PD-L1-positive TNBC under Japanese medical conditions and environments using a Markov model.
CD40- and 41BB-specific antibody fusion proteins with PDL1 blockade-restricted agonism. [2022]Background: A strategy to broaden the applicability of checkpoint inhibitors is the combined use with antibodies targeting the immune stimulatory receptors CD40 and 41BB. However, the use of anti-CD40 and anti-41BB antibodies as agonists is problematic in two ways. First, anti-CD40 and anti-41BB antibodies need plasma membrane-associated presentation by FcγR binding to exert robust agonism but this obviously limits their immune stimulatory efficacy by triggering ADCC, CDC or anti-inflammatory FcγRIIb activities. Second, off tumor activation of CD40 and 41BB may cause dose limiting systemic inflammation. Methods: To overcome the FcγR-dependency of anti-41BB and anti-CD40 antibodies, we genetically fused such antibodies with a PDL1-specific blocking scFv as anchoring domain to enable FcγR-independent plasma membrane-associated presentation of anti-CD40- and anti-41BB antibodies. By help of GpL-tagged variants of the resulting bispecific antibodies, binding to their molecular targets was evaluated by help of cellular binding studies. Membrane PDL1-restricted engagement of CD40 and 41BB but also inhibition of PDL1-induced PD1 activation were evaluated in coculture assays with PDL1-expressing tumor cell lines and 41BB, CD40 and PD1 responsible cell lines or T-cells. Results: The binding properties of the bispecific antibody fusion proteins remained largely unchanged compared to their parental molecules. Upon anchoring to membrane PDL1, the bispecific antibody fusion proteins activated CD40/41BB signaling as efficient as the parental anti-CD40/anti-41BB antibodies when bound to FcγRs or cells expressing membrane-bound CD40L/41BBL. PD1 inhibition remained intact and the anti-41BB fusion protein thus showed PDL1-restricted costimulation of T-cells activated in vitro with anti-CD3 or a BiTe. Conclusions: Targeting of anti-CD40 and anti-41BB fusion proteins to membrane PDL1 with a blocking PDL1 scFv links PD1-PDL1 checkpoint blockade intrinsically with engagement of CD40 or 41BB.
Dermatological adverse events associated with immune checkpoint inhibitor-based combinations of anticancer therapies: a systematic review. [2022]Aim: This paper presents the reported dermatological adverse events (AEs) associated with approved combinations of immunotherapy with drugs of the same class, or in combination with targeted therapy or chemotherapy. Materials & methods: PubMed was used as an electronic database, and a total of 29 articles were reviewed which reported dermatological AEs following combination therapies with nivolumab, ipilimumab, axitinib, pembrolizumab, lenvatinib, avelumab, atezolizumab, carboplatin, etoposide, paclitaxel, bevacizumab, pemetrexed, cisplatin and durvalumab. Results: The dermatological AEs reported were mutually inclusive and the highest incidence of specific AEs was seen in the following combinations: rash in the nivolumab/ipilimumab and lenvatinib/pembrolizumab combinations, pruritus in the atezolizumab/nab-paclitaxel combination, dry skin and palmar-plantar erythrodysesthesia in the axitinib/pembrolizumab combination, and alopecia and severe skin reactions in the pembrolizumab/carboplatin/paclitaxel combination. Conclusion: Knowledge of such side effects is of benefit when choosing an optimal treatment regimen and should be integrated into the monitoring and follow-up phases of treatment.
DuoBody-CD40x4-1BB induces dendritic-cell maturation and enhances T-cell activation through conditional CD40 and 4-1BB agonist activity. [2022]Despite the preclinical promise of CD40 and 4-1BB as immuno-oncology targets, clinical efforts evaluating CD40 and 4-1BB agonists as monotherapy have found limited success. DuoBody-CD40×4-1BB (GEN1042/BNT312) is a novel investigational Fc-inert bispecific antibody for dual targeting and conditional stimulation of CD40 and 4-1BB to enhance priming and reactivation of tumor-specific immunity in patients with cancer.
Risks and safety of biologics: A practical guide for allergists. [2023]Biologic agents are a rapidly expanding class of medications, and several options are now available for the management of allergic and immunologic disorders. The risks of biologic therapy need to be understood in order to adequately counsel patients and appropriately monitor for potential adverse events. We sought to provide a comprehensive review of the risks and adverse effects reported for the current FDA-approved biologics used in management of allergic and immunologic disorders, including omalizumab, benralizumab, dupilumab, mepolizumab, reslizumab, tezepelumab and tralokinumab. Our review focuses on the risk of hypersensitivity reactions, pregnancy-specific considerations, risk of infection and risk of malignancy. We also highlight drug-specific adverse events and unique safety issues identified in case reports.
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]Additional immunotherapies are still warranted for non-responders to checkpoint inhibitors with refractory or relapsing cancers, especially for patients with "cold" tumours lacking significant immune infiltration at treatment onset. We developed XFab-α4-1BB/CD40L, a bispecific antibody targeting 4-1BB and CD40 for dendritic cell activation and priming of tumour-reactive T cells to inhibit tumours.