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Study to Assess Adverse Events and Change in Disease Activity in Adult Participants With Select Advanced Solid Tumor Indications Receiving Intravenous (IV) ABBV-400

Phase 1
Recruiting
Conditions
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
Interventions
Registration Number
NCT06084481
Lead Sponsor
AbbVie
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
285
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Cohort 1: Hepatocellular Carcinoma (HCC)ABBV-400Participants with HCC will receive ABBV-400 for up to 3 years during and up to the treatment period with an additional safety follow-up period of up to 2 years.
Cohort 2: Pancreatic Ductal Adenocarcinoma (PDAC)ABBV-400Participants with PDAC will receive ABBV-400 for up to 3 years during and up to the treatment period with an additional safety follow-up period of up to 2 years.
Cohort 3: Biliary Tract Cancers (BTC)ABBV-400Participants with BTC will receive ABBV-400 for up to 3 years during and up to the treatment period with an additional safety follow-up period of up to 2 years.
Cohort 4: Esophageal Squamous Cell Carcinoma, (ESCC)ABBV-400Participants with ESCC will receive ABBV-400 for up to 3 years during and up to the treatment period with an additional safety follow-up period of up to 2 years.
Cohort 5: Triple Negative Breast Cancer (TNBC)ABBV-400Participants with TNBC will receive ABBV-400 for up to 3 years during and up to the treatment period with an additional safety follow-up period of up to 2 years.
Cohort 6: Hormone Receptor+/HER2-breast Cancer (HR+/HER2-BC)ABBV-400Participants with HR+/HER2-BC will receive ABBV-400 for up to 3 years during and up to the treatment period with an additional safety follow-up period of up to 2 years.
Cohort 7: Head and Neck Squamous-cell-carcinoma (HNSCC)ABBV-400Participants with HNSCC will receive ABBV-400 for up to 3 years during and up to the treatment period with an additional safety follow-up period of up to 2 years.
Cohort 8: PROC/Primary Peritoneal/Fallopian Tube CancerABBV-400Participants with Platinum Resistant High Grade Epithelial Ovarian Cancer (PROC)/primary peritoneal/fallopian tube cancer will receive ABBV-400 for up to 3 years during and up to the treatment period with an additional safety follow-up period of up to 2 years.
Cohort 9: Drug-Drug InteractionABBV-400Participants with advanced or metastatic solid tumors will receive ABBV-400 and a strong CYP3A4 inhibitor (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.
Cohort 9: Drug-Drug InteractionItraconazole (ITZ)Participants with advanced or metastatic solid tumors will receive ABBV-400 and a strong CYP3A4 inhibitor (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.
Primary Outcome Measures
NameTimeMethod
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.

Maximum Observed Concentration (Cmax) of ABBV-400 ConjugateUp to 36 Months

Cmax of ABBV-400 conjugate.

AUC from Time 0 to the End of Dosing Interval (AUCtau) of ABBV-400 ConjugateUp to 36 Months

AUCtau of ABBV-400 conjugate.

Secondary Outcome Measures
NameTimeMethod
Duration of Response (DOR) for Participants with Confirmed Complete Response (CR)/PRUp 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 RateUp 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-400Up to 36 Months

Cmax of ABBV-400.

Time to Cmax (Tmax) of ABBV-400Up to 36 Months

Tmax of ABBV-400.

Area Under the Plasma Concentration-time Curve (AUC) for Total Antibody ConcentrationUp to 36 Months

AUC for total antibody concentration.

Total Antibody Drug Conjugate (ADC) ConcentrationUp to 36 Months

Total ADC concentration.

Plasma Concentrations of Unconjugated Topoisomerase 1 (Top1) Inhibitor PayloadUp to 36 Months

Plasma concentrations of unconjugated Top1 inhibitor payload.

Antidrug Antibody (ADA)Up to 36 Months

Incidence and concentration of anti-drug antibodies.

Neutralizing Antidrug Antibody (nADA)Up to 36 Months

Incidence and concentration of neutralizing anti-drug antibodies.

Tmax of ABBV-400 ConjugateUp to 36 Months

Tmax of ABBV-400 conjugate.

Tmax of ABBV-400 UnconjugatedUp to 36 Months

Tmax of ABBV-400 unconjugated.

Terminal Phase Elimination Half-Life (t1/2) of ABBV-400 ConjugateUp to 36 Months

t1/2 of ABBV-400 conjugate.

t1/2 of ABBV-400 UnonjugatedUp to 36 Months

t1/2 of ABBV-400 unconjugated.

Volume of Distribution at Steady State (Vss) of ABBV-400 ConjugateUp to 36 Months

Vss of ABBV-400 conjugate.

Vss of ABBV-400 UnconjugatedUp to 36 Months

Vss of ABBV-400 unconjugated.

Total Body Clearance at Steady State (CLss) of ABBV-400 ConjugateUp to 36 Months

CLss of ABBV-400 conjugate.

CLss of ABBV-400 UnconjugatedUp to 36 Months

CLss of ABBV-400 unconjugated.

Trial Locations

Locations (54)

City of Hope National Medical Center /ID# 258645

🇺🇸

Duarte, California, United States

Ucsf /Id# 257705

🇺🇸

San Francisco, California, United States

University of Colorado Cancer Center - Cancer Clinical Trials Office /ID# 255128

🇺🇸

Aurora, Colorado, United States

Sarah Cannon Research Institute at HealthONE - Denver /ID# 258926

🇺🇸

Denver, Colorado, United States

Florida Cancer Specialists /ID# 261569

🇺🇸

Sarasota, Florida, United States

Northwestern University Feinberg School of Medicine /ID# 257378

🇺🇸

Chicago, Illinois, United States

University of Chicago Medical Center /ID# 258197

🇺🇸

Chicago, Illinois, United States

START Midwest /ID# 256581

🇺🇸

Grand Rapids, Michigan, United States

Washington University-School of Medicine /ID# 257379

🇺🇸

St Louis, Missouri, United States

Memorial Sloan Kettering Cancer Center-Koch Center /ID# 255132

🇺🇸

New York, New York, United States

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City of Hope National Medical Center /ID# 258645
🇺🇸Duarte, California, United States

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