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 1Active Not RecruitingNCT06084481

AbbVie302 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

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

Outcomes

Primary Outcomes

Objective Response Rate (ORR)

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.

Time frame: Up to 36 Months

Number of Participants with Adverse Events (AEs)

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.

Time frame: Up to 36 Months

Maximum Observed Concentration (Cmax) of ABBV-400 Conjugate

Cmax of ABBV-400 conjugate.

Time frame: Up to 36 Months

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

AUCtau of ABBV-400 conjugate.

Time frame: Up to 36 Months

Secondary Outcomes

Duration of Response (DOR) for Participants with Confirmed Complete Response (CR)/PR

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.

Time frame: Up to 36 Months

Clinical Benefit Rate

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

Time frame: Up to 36 Months

Progression-free Survival (PFS)

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.

Time frame: Up to 36 Months

Overall Survival (OS)

OS is defined as time from first study treatment to death due to any cause.

Time frame: Up to 36 Months

Cmax of ABBV-400

Cmax of ABBV-400.

Time frame: Up to 36 Months

Time to Cmax (Tmax) of ABBV-400

Tmax of ABBV-400.

Time frame: Up to 36 Months

Area Under the Plasma Concentration-time Curve (AUC) for Total Antibody Concentration

AUC for total antibody concentration.

Time frame: Up to 36 Months

Total Antibody Drug Conjugate (ADC) Concentration

Total ADC concentration.

Time frame: Up to 36 Months

Plasma Concentrations of Unconjugated Topoisomerase 1 (Top1) Inhibitor Payload

Plasma concentrations of unconjugated Top1 inhibitor payload.

Time frame: Up to 36 Months

Antidrug Antibody (ADA)

Incidence and concentration of anti-drug antibodies.

Time frame: Up to 36 Months

Neutralizing Antidrug Antibody (nADA)

Incidence and concentration of neutralizing anti-drug antibodies.

Time frame: Up to 36 Months

Tmax of ABBV-400 Conjugate

Tmax of ABBV-400 conjugate.

Time frame: Up to 36 Months

Tmax of ABBV-400 Unconjugated

Tmax of ABBV-400 unconjugated.

Time frame: Up to 36 Months

Terminal Phase Elimination Half-Life (t1/2) of ABBV-400 Conjugate

t1/2 of ABBV-400 conjugate.

Time frame: Up to 36 Months

t1/2 of ABBV-400 Unonjugated

t1/2 of ABBV-400 unconjugated.

Time frame: Up to 36 Months

Volume of Distribution at Steady State (Vss) of ABBV-400 Conjugate

Vss of ABBV-400 conjugate.

Time frame: Up to 36 Months

Vss of ABBV-400 Unconjugated

Vss of ABBV-400 unconjugated.

Time frame: Up to 36 Months

Total Body Clearance at Steady State (CLss) of ABBV-400 Conjugate

CLss of ABBV-400 conjugate.

Time frame: Up to 36 Months

CLss of ABBV-400 Unconjugated

CLss of ABBV-400 unconjugated.

Time frame: Up to 36 Months

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

Overview

Conditions

Interventions

Eligibility

Locations (54)

Outcomes

Primary Outcomes

Secondary Outcomes