Hepatocellular Carcinoma, Pancreatic Ductal Adenocarcinoma, Biliary Tract Cancers, Esophageal Squamous Cell Carcinoma, Triple Negative Breast Cancer, Hormone Receptor+/Human Epidermal Growth Factor Receptor 2 Negative Breast Cancer, Head and Neck Squamous-Cell Carcinoma, Platinum Resistant High Grade Epithelial Ovarian Cancer
Conditions
Keywords
Hepatocellular Carcinoma, Pancreatic Ductal Adenocarcinoma, Biliary Tract Cancers, Esophageal Squamous Cell Carcinoma, Triple Negative Breast Cancer, Hormone Receptor+/Human Epidermal Growth Factor Receptor 2 Negative Breast Cancer, Head and Neck Squamous-Cell Carcinoma, Platinum Resistant High Grade Epithelial Ovarian Cancer, Solid Tumors, Advanced Solid Tumors, ABBV-400
Brief summary
Cancer is a condition where cells in a specific part of body grow and reproduce uncontrollably. The purpose of this study is to assess adverse events and change in disease activity when ABBV-400 is given to adult participants to treat advanced solid tumors. ABBV-400 is an investigational drug being developed for the treatment of advanced solid tumors. Study doctors put the participants in groups called cohorts. Cohorts 1-8 receive ABBV-400 alone (monotherapy) followed by a safety follow-up period. Cohort 9 receives ABBV-400 in combination with a strong CYP3A3 inhibitor (ITZ) followed by a safety follow-up period. Approximately 285 adult participants with hepatocellular carcinoma (HCC), pancreatic ductal adenocarcinoma (PDAC), biliary tract cancers (BTC), esophageal squamous cell carcinoma (ESCC), triple negative breast cancer (TNBC), hormone receptor+/human epidermal growth factor receptor 2 negative (HER2-) breast cancer (hormone receptor-positive \[HR+\]/HER2-breast cancer \[BC\]), head and neck squamous-cell-carcinoma (HNSCC), Platinum Resistant High Grade Epithelial Ovarian Cancer (PROC)/primary peritoneal/fallopian tube cancer, or advanced solid tumors, will be enrolled in the study in approximately 54 sites worldwide. In cohorts 1-8, participants with the following advanced solid tumor indications: HCC, PDAC, BTC, ESCC, TNBC, HR+/HER2-BC, HNSCC, and PROC/primary peritoneal/fallopian tube cancer will receive intravenous (IV) ABBV-400 monotherapy and in cohort 9 participants will receive intravenous (IV) ABBV-400 and an oral solution of ITZ, for up to 3 years during and up to the treatment period with an additional safety follow-up period of up to 2 years. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.
Interventions
DRUGABBV-400
Intravenous (IV) Infusion
Oral Solution
Sponsors
AbbVie
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Laboratory values meeting the criteria laid out in the protocol. * Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. * Documented diagnosis of locally advanced or metastatic hepatocellular carcinoma (HCC), pancreatic ductal adenocarcinoma (PDAC), biliary tract cancers (BTC), squamous cell carcinoma of the esophagus, (ESCC), triple negative breast cancer (TNBC), hormone receptor+/HER2-breast cancer (HR+/HER2-BC), head and neck squamous-cell-carcinoma (HNSCC), or Platinum Resistant High Grade Epithelial Ovarian Cancer (PROC)/primary peritoneal/fallopian tube cancer (by World Health Organization \[WHO\] criteria). Participant meets the criteria for disease activity laid out in the protocol.
Exclusion criteria
* Have received anticancer therapy including chemotherapy, radiation therapy, immunotherapy, biologic, or any investigational therapy within 28 days or 5 half-lives of the drug (whichever is shorter) prior to the first dose of ABBV-400. Palliative radiation therapy for bone, skin, or subcutaneous metastases with 10 fractions or less is permitted and not subject to a washout period. * Unresolved clinically significant AEs \> Grade 1 from prior anticancer therapy. * History of interstitial lung disease (ILD) or pneumonitis that required treatment with systemic steroids, or any evidence of active ILD or pneumonitis, including but not limited to those listed in the protocol. * History of clinically significant, intercurrent lung-specific illnesses, including those laid out in the protocol. * Untreated brain or meningeal metastases (i.e., participants with history of metastases are eligible provided they do not require ongoing steroid treatment for cerebral edema and have shown clinical and radiographic stability for at least 14 days after definitive therapy). Participants may continue on antiepileptic therapy if required. * History of other active malignancy, with the exception of those laid out in the protocol. * Any autoimmune, connective tissue or inflammatory disorders with documented or suspicious pulmonary involvement at screening (i.e., rheumatoid arthritis, Sjogren's, sarcoidosis etc.), and prior pneumonectomy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Concentration (Cmax) of ABBV-400 Conjugate | Up to 36 Months | Cmax of ABBV-400 conjugate. |
| AUC from Time 0 to the End of Dosing Interval (AUCtau) of ABBV-400 Conjugate | Up to 36 Months | AUCtau of ABBV-400 conjugate. |
| Objective Response Rate (ORR) | Up to 36 Months | ORR defined as percentage of participants with confirmed best overall response of confirmed partial response (PR) or better per investigator review according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. |
| Number of Participants with Adverse Events (AEs) | Up to 36 Months | An AE is defined as any untoward medical occurrence in a patient or clinical investigation in which a participant is administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| t1/2 of ABBV-400 Unonjugated | Up to 36 Months | t1/2 of ABBV-400 unconjugated. |
| Volume of Distribution at Steady State (Vss) of ABBV-400 Conjugate | Up to 36 Months | Vss of ABBV-400 conjugate. |
| Vss of ABBV-400 Unconjugated | Up to 36 Months | Vss of ABBV-400 unconjugated. |
| Total Body Clearance at Steady State (CLss) of ABBV-400 Conjugate | Up to 36 Months | CLss of ABBV-400 conjugate. |
| CLss of ABBV-400 Unconjugated | Up to 36 Months | CLss of ABBV-400 unconjugated. |
| Duration of Response (DOR) for Participants with Confirmed Complete Response (CR)/PR | Up to 36 Months | DOR is defined for participants achieving a confirmed PR or better as the time from the initial response of PR (or better) per investigator review according to RECIST 1.1 criteria to disease progression or death of any cause, whichever occurs earlier. |
| Clinical Benefit Rate | Up to 36 Months | CBR is defined as the proportion of participants with a best overall response of stable disease at least 5 weeks post first dose, confirmed CR or PR per investigator review according to RECIST, version 1.1 |
| Progression-free Survival (PFS) | Up to 36 Months | PFS is defined as time from first study treatment to a documented disease progression according to RECIST, version 1.1, as determined by the investigator, or death due to any cause, whichever occurs earlier. |
| Overall Survival (OS) | Up to 36 Months | OS is defined as time from first study treatment to death due to any cause. |
| Cmax of ABBV-400 | Up to 36 Months | Cmax of ABBV-400. |
| Time to Cmax (Tmax) of ABBV-400 | Up to 36 Months | Tmax of ABBV-400. |
| Area Under the Plasma Concentration-time Curve (AUC) for Total Antibody Concentration | Up to 36 Months | AUC for total antibody concentration. |
| Total Antibody Drug Conjugate (ADC) Concentration | Up to 36 Months | Total ADC concentration. |
| Plasma Concentrations of Unconjugated Topoisomerase 1 (Top1) Inhibitor Payload | Up to 36 Months | Plasma concentrations of unconjugated Top1 inhibitor payload. |
| Neutralizing Antidrug Antibody (nADA) | Up to 36 Months | Incidence and concentration of neutralizing anti-drug antibodies. |
| Antidrug Antibody (ADA) | Up to 36 Months | Incidence and concentration of anti-drug antibodies. |
| Tmax of ABBV-400 Conjugate | Up to 36 Months | Tmax of ABBV-400 conjugate. |
| Tmax of ABBV-400 Unconjugated | Up to 36 Months | Tmax of ABBV-400 unconjugated. |
| Terminal Phase Elimination Half-Life (t1/2) of ABBV-400 Conjugate | Up to 36 Months | t1/2 of ABBV-400 conjugate. |
Countries
Australia, Israel, Japan, Puerto Rico, South Korea, Spain, Taiwan, United States
Contacts
STUDY_DIRECTORABBVIE INC.
AbbVie
Outcome results
None listed