Study to Evaluate Adverse Events and Change in Disease Activity When Intravenous (IV) Infusion of ABBV-927 is Administered in Combination With IV Modified FOLFIRINOX (mFFX) With or Without IV Budigalimab Compared to mFFX in Adult Participants With Untreated Pancreatic Cancer Metastasis

Sponsor

AbbVie (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04807972

Collaborator

(none)

129

Enrollment

Locations

Arms

48.6

Anticipated Duration (Months)

5.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Metastatic Pancreatic Cancer Disease is one of the most aggressive and deadliest forms of cancer with very poor survival. This study will evaluate adverse events and change in disease activity in participants 18 to 75 years of age with a body weight greater than or equal to 35 kg with Metastatic Pancreatic Cancer Disease treated with Intravenous (IV) infusion of modified FOLFIRINOX (mFFX) combined with IV infusions of ABBV-927 with or without Budigalimab.

ABBV-927 and Budigalimab are the investigational drugs being developed for treatment of Metastatic Pancreatic Cancer Disease. In this study, doctors will enroll participants between 18 and 75 years of age with a body weight greater than or equal to 35 kg diagnosed diagnosed with Metastatic Pancreatic Cancer Disease in 4 different groups, called treatment arms. Each group will receive different treatments. Approximately 129 adult participants will be enrolled in the study across approximately 27 sites worldwide.

Participants will receive ABBV-927 and Budigalimab as Intravenous (IV) Infusion in Phase 1b and Phase 2 on day 3 of every 28 day cycle, modified FOLFIRINOX as IV Infusion in Phase 1b and Phase 2 on Day1 and Day 15 of every 28 day cycle up to maximum of 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 a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Cancer	Drug: ABBV-927 Drug: Budiglimab Drug: modified FOLFIRINOX	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

129 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1b/2, Randomized, Controlled, Open-Label Study Evaluating the Safety and Efficacy of ABBV-927 Administered in Combination With Modified FOLFIRINOX (mFFX) With or Without Budigalimab Compared to mFFX in Subjects With Untreated Metastatic Pancreatic Adenocarcinoma

Actual Study Start Date :

May 28, 2021

Anticipated Primary Completion Date :

Aug 3, 2024

Anticipated Study Completion Date :

Jun 15, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 1b Dose Escalation Participants will receive escalating doses of ABBV-927 in combination with modified FOLFIRINOX (mFFX) and Budigalimab.	Drug: ABBV-927 Intravenous (IV) Infusion Drug: Budiglimab Intravenous (IV) Infusion Other Names: ABBV-181 Drug: modified FOLFIRINOX Intravenous (IV) Infusion Other Names: mFFX
Experimental: Phase 2 Cohort A Participants will receive modified FOLFIRINOX on Day 1 and Day 15 of each 28 day cycle.	Drug: modified FOLFIRINOX Intravenous (IV) Infusion Other Names: mFFX
Experimental: Phase 2 Cohort B Participants will receive modified FOLFIRINOX (Day 1 and Day 15) + ABBV-927 in each 28 day cycle.	Drug: ABBV-927 Intravenous (IV) Infusion Drug: modified FOLFIRINOX Intravenous (IV) Infusion Other Names: mFFX
Experimental: Phase 2 Cohort C Expansion Participants will receive modified FOLFIRINOX (Day 1 and Day 15) + ABBV 927 and Budigalimab as Intravenous (IV) Infusion in each 28 day cycle.	Drug: ABBV-927 Intravenous (IV) Infusion Drug: Budiglimab Intravenous (IV) Infusion Other Names: ABBV-181 Drug: modified FOLFIRINOX Intravenous (IV) Infusion Other Names: mFFX

Outcome Measures

Primary Outcome Measures

Phase 1b: Percentage of participants experiencing Adverse Events [Up to 6 months]
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related.
Phase 1b: Number of Participants with Potentially Clinically Significant (PCS) Laboratory (Hematological and Chemistry) Values [Up to 6 months]
Baseline values and changes from baseline will be summarized for each scheduled post-baseline visit for laboratory data as applicable. If more than one measurement exists for a participant on a particular day and time, an arithmetic average will be calculated. This average will be that participant's measurement for that day. For participants that do not have any post-baseline measurements, only their baseline values will be summarized.
Phase 1b: Number of Participants with Potentially Clinically Significant (PCS) Vital Signs [Up to 6 months]
Baseline values and changes from baseline will be summarized for each scheduled post-baseline visit for vital signs data.
Phase 1b: Number of Participants with Dose Limiting Toxicities (DLT) [Up to 6 months]
A DLT is defined as any serious AE for which a clear alternative cause cannot be established (e.g., attributed to the disease under study, another disease, or to a concomitant medication [e.g., COVID-19 vaccine] by the investigator or AbbVie Therapeutic Area (TA) MD] that occurs during the DLT observation period, and is not listed as a predefined exception in the protocol.
Phase 2: Overall Survival [48 months.]
Overall survival is defined as the time between the date of randomization and death due to any cause.

Secondary Outcome Measures

Phase 1b and Phase 2: Maximum Plasma Concentration (Cmax) [Up to approximately 3 months]
The maximum plasma concentration (Cmax; measured in ng/mL) is the highest concentration that a drug achieves in the blood after administration in a dosing interval.
Phase 1b and Phase 2: Time to Maximum Observed Plasma Concentration (Tmax) [Up to approximately 3 months]
The time to maximum plasma concentration (Tmax; measured in hours) is the time it takes for a drug to achieve Cmax.
Phase 1b and Phase 2: Area Under the Concentration-time Curve Over the Time Interval (AUC) in Plasma [Up to approximately 3 months.]
The area under the plasma concentration-time curve (AUC; measured in ng*hr/mL) is a method of measurement of the total exposure of a drug in blood plasma.
Phase 1b and Phase 2: Objective Response Rate (ORR) [Up to approximately 27 months]
ORR is defined as the percentage of participants whose best overall response is either complete response (CR) or partial response (PR) per investigator assessment according to RECIST version 1.1.
Phase 1b and Phase 2: Clinical Benefit Rate (CBR) [Up to approximately 27 months]
Clinical Benefit Rate (CBR) is defined as the percentage of participants whose best overall response is either Complete Response (CR), Partial Response (PR), or stable disease (SD) according to RECIST version 1.1.
Phase 1b and Phase 2: Duration of Response (DOR) for Participants Who Achieve a Documented Confirmed Response of CR/PR [Up to approximately 27 months]
DOR is defined as the time from the initial response of CR/PR per investigator review according to RECIST version 1.1 criteria to the first occurrence of radiographic disease progression, clinical progression or death from any cause whichever occurs first.
Phase 1b and Phase 2: Progression Free Survival (PFS) [Up to approximately 24 months after study drug discontinuation]
PFS is defined as the time from randomization to a documented radiographic disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, clinical progression or death from any cause, whichever occurs earlier.
Phase 1b and Phase 2: Quality of Life(QoL)-Measure Participant Overall Perceptions of Their Change in Pancreatic Cancer Symptoms includes the Patient Global Impression of Severity (PGIS) and the the Patient Global Impression of Change (PGIC) [Up to approximately 25 months]
Patient Global Impression of Severity (PGIS) and Patient Global Impression of Change (PGIC) will measure participants' overall perceptions of their pancreatic cancer symptoms over time.
Phase 2: Percentage of Participants Experiencing Adverse Events [Up to approximately 27 months.]
An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Body weight >= 35 kg.
Histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma with metastatic disease.
Measurable disease per Response Evaluation Criteria for Solid Tumors Version 1.1 (RECIST v1.1).
Prior history of or clinically stable concurrent malignancy are eligible for enrollment provided the malignancy is clinically insignificant, no treatment is required, and the participant is clinically stable.

Exclusion Criteria:

Participants with locally advanced disease.
Participants with neuroendocrine (carcinoid, islet cell) or acinar pancreatic carcinoma.
Prior radiotherapy, surgery, or systemic anti-cancer therapy for the treatment of metastatic pancreatic adenocarcinoma.
Prior radiotherapy, surgery, or systemic anti-cancer therapy in the adjuvant setting, or earlier, within the last 4 months.
Prior radiotherapy to any measurable metastatic lesion at any time.
Clinically significant third-space fluid accumulation (e.g., ascites or pleural effusion).
Known metastases to the central nervous system (CNS).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Highlands Oncology Group Springdale /ID# 242049	Springdale	Arkansas	United States	72762
2	UCHSC Anschultz Cancer Pavilion /ID# 227841	Aurora	Colorado	United States	80045-2517
3	Yale University, Yale Cancer Center /ID# 227685	New Haven	Connecticut	United States	06510-3206
4	NW Georgia Oncology Centers /ID# 241146	Marietta	Georgia	United States	30060
5	The University of Chicago Medical Center /ID# 229081	Chicago	Illinois	United States	60637-1443
6	Johns Hopkins University /ID# 226713	Baltimore	Maryland	United States	21287
7	Univ Hosp Cleveland /ID# 226807	Cleveland	Ohio	United States	44106
8	Cleveland Clinic Main Campus /ID# 231135	Cleveland	Ohio	United States	44195
9	Kettering Adventist Healthcare /ID# 243860	Kettering	Ohio	United States	45429-1221
10	Penn State Hershey Medical Ctr /ID# 229837	Hershey	Pennsylvania	United States	17033-2360
11	Monash Medical Centre /ID# 231379	Clayton	Victoria	Australia	3168
12	Austin Health /ID# 231378	Heidelberg	Victoria	Australia	3084
13	The Chaim Sheba Medical Center /ID# 226812	Ramat Gan	Tel-Aviv	Israel	5265601
14	Rambam Health Care Campus /ID# 229555	Haifa		Israel	3109601
15	Yonsei University Health System Severance Hospital /ID# 230280	Seoul	Seoul Teugbyeolsi	Korea, Republic of	03722
16	Seoul National University Hospital /ID# 230278	Seoul		Korea, Republic of	03080
17	Asan Medical Center /ID# 230282	Seoul		Korea, Republic of	05505
18	Samsung Medical Center /ID# 230283	Seoul		Korea, Republic of	06351
19	Hematology and Oncology Institute /ID# 230572	Manati		Puerto Rico	00674
20	Pan American Center for Oncology Trials, LLC /ID# 228210	Rio Piedras		Puerto Rico	00935
21	Instituto Catalan de Oncologia (ICO) L'Hospitalet /ID# 230138	Hospitalet de Llobregat	Barcelona	Spain	08908
22	Hospital Universitario Vall d'Hebron /ID# 230226	Barcelona		Spain	08035
23	Hospital Universitario 12 de Octubre /ID# 230102	Madrid		Spain	28041
24	Hospital Universitario Miguel Servet /ID# 230139	Zaragoza		Spain	50009