A Study to Evaluate the Adverse Events, Efficacy, and Optimal Dose of Intravenous (IV) Telisotuzumab Adizutecan in Combination With IV Budigalimab in Adult Participants With Advanced or Metastatic Non-Squamous NSCLC With No Prior Treatment for Advanced Disease, and No Actionable Genomic Alterations

Phase 1

Recruiting

• Conditions: Non Small Cell Lung Carcinoma
• Interventions: Drug: Pembrolizumab; Drug: Telisotuzumab Adizutecan; Drug: Budigalimab; Drug: Carboplatin; Drug: Pemetrexed; Drug: Cisplatin

• Registration Number: NCT06772623
• Lead Sponsor: AbbVie

Brief Summary

Non small cell lung carcinoma (NSCLC) is the most frequently occurring histologic subtype of lung cancer and is the leading cause of cancer-related deaths worldwide. The purpose of this study is to assess adverse events and change in disease activity when Telisotuzumab Adizutecan (ABBV-400) is given in combination with a programmed cell death receptor 1 (PD1) inhibitor (budigalimab) to adult participants to treat NSCLC.

ABBV-400 and budigalimab are investigational drugs being developed for the treatment of NSCLC. This study will be divided into two stages, with the first stage treating participants with several doses of ABBV-400 in combination with budigalimab within the dose escalation regimen until the dose reached is tolerable and expected to be efficacious. In Stage 2 there will be 4 treatment groups. Two groups will receive budigalimab with different optimized doses of telisotuzumab adizutecan (to allow for the best dose to be studied in the future). One group will receive budigalimab, pemetrexed, and investigator's choice of carboplatin or cisplatin, followed by budigalimab and pemetrexed. One group will receive the standard of care (SOC) pembrolizumab, pemetrexed, and investigator's choice of carboplatin or cisplatin, followed by pembrolizumab and pemetrexed. Approximately 172 adult participants with NSCLC will be enrolled in the study in 132 sites worldwide.

In the dose escalation stage participants will be treated with increasing intravenous (IV) doses of Telisotuzumab Adizutecan in combination with budigalimab until the dose of Telisotuzumab Adizutecan reached is tolerable and expected to be efficacious. In the dose optimization stage participants will be receive IV optimized doses of Telisotuzumab Adizutecan in combination with budigalimab or receive IV budigalimab, pemetrexed, and investigator's choice of carboplatin or cisplatin, followed by budigalimab and pemetrexed, or IV SOC pembrolizumab, pemetrexed, and investigator's choice of carboplatin or cisplatin, followed by pembrolizumab and pemetrexed. The study will run for a duration of approximately 33 months.

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

Study Timeline

• Study First Submitted: 2025-01-09
• Study First Submitted QC: 2025-01-09
• Study First Posted: 2025-01-13
• Study Start: 2025-03-06
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-14
• Last Update Posted: 2025-05-16
• Primary Completion: 2027-11
• Study Completion: 2027-11

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 172

Inclusion Criteria

• Must have histologically documented non-squamous (NSq) non small cell lung carcinoma (NSCLC) that is locally advanced or metastatic will be enrolled into the study.
• Must have measurable disease per response evaluation criteria in solid tumors (RECIST) v1.1.
• For Part 1, participants must have had no more than 1 systemic therapy for advanced disease including platinum-based chemotherapy or an immune checkpoint inhibitor (as monotherapy or in combination with chemotherapy), or appropriate targeted therapy for an actionable gene alteration, if applicable, for epidermal growth factor receptor (EGFR) wild-type (WT) NSq NSCLC.
• For Part 2, participants must have no prior systemic therapy for advanced disease, no known actionable genomic alteration.
• Must have documented programmed death ligand 1 (PD-L1) status.
• Must have adequate organ function.

Exclusion Criteria

• Known uncontrolled metastases to the central nervous system.
• History of interstitial lung disease (ILD) or pneumonitis that required treatment with systemic steroids, or any evidence of active ILD or pneumonitis on screening chest computed tomography (CT) scan.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part 1: Telisotuzumab Adizutecan + Budigalimab	Budigalimab	Participants will receive several doses of telisotuzumab adizutecan in combination with budigalimab, as part of the 33 month study duration.
Part 2 Arm 1: Telisotuzumab Adizutecan + Budigalimab Dose A	Budigalimab	Participants will receive telisotuzumab adizutecan dose A in combination with budigalimab, as part of the 33 month study duration.
Part 2 Arm 2: Telisotuzumab Adizutecan + Budigalimab Dose B	Budigalimab	Participants will receive telisotuzumab adizutecan dose B in combination with budigalimab, as part of the 33 month study duration.
Part 2 Arm 3: Budigalimab +	Budigalimab	Participants will receive budigalimab, pemetrexed, and investigator's choice of carboplatin or cisplatin, followed by budigalimab and pemetrexed, as part of the 33 month study duration.
Part 2 Arm 3: Budigalimab +	Carboplatin	Participants will receive budigalimab, pemetrexed, and investigator's choice of carboplatin or cisplatin, followed by budigalimab and pemetrexed, as part of the 33 month study duration.
Part 2 Arm 3: Budigalimab +	Pemetrexed	Participants will receive budigalimab, pemetrexed, and investigator's choice of carboplatin or cisplatin, followed by budigalimab and pemetrexed, as part of the 33 month study duration.
Part 2 Arm 3: Budigalimab +	Cisplatin	Participants will receive budigalimab, pemetrexed, and investigator's choice of carboplatin or cisplatin, followed by budigalimab and pemetrexed, as part of the 33 month study duration.
Part 2: Standard of Care	Pembrolizumab	Participants will receive pembrolizumab, pemetrexed, and investigator's choice of carboplatin or cisplatin, followed by pembrolizumab and pemetrexed, as part of the 33 month study duration.
Part 2: Standard of Care	Carboplatin	Participants will receive pembrolizumab, pemetrexed, and investigator's choice of carboplatin or cisplatin, followed by pembrolizumab and pemetrexed, as part of the 33 month study duration.
Part 2: Standard of Care	Pemetrexed	Participants will receive pembrolizumab, pemetrexed, and investigator's choice of carboplatin or cisplatin, followed by pembrolizumab and pemetrexed, as part of the 33 month study duration.
Part 2: Standard of Care	Cisplatin	Participants will receive pembrolizumab, pemetrexed, and investigator's choice of carboplatin or cisplatin, followed by pembrolizumab and pemetrexed, as part of the 33 month study duration.
Part 1: Telisotuzumab Adizutecan + Budigalimab	Telisotuzumab Adizutecan	Participants will receive several doses of telisotuzumab adizutecan in combination with budigalimab, as part of the 33 month study duration.
Part 2 Arm 1: Telisotuzumab Adizutecan + Budigalimab Dose A	Telisotuzumab Adizutecan	Participants will receive telisotuzumab adizutecan dose A in combination with budigalimab, as part of the 33 month study duration.
Part 2 Arm 2: Telisotuzumab Adizutecan + Budigalimab Dose B	Telisotuzumab Adizutecan	Participants will receive telisotuzumab adizutecan dose B in combination with budigalimab, as part of the 33 month study duration.

Primary Outcome Measures

Name	Time	Method
Part 1: Dose-Limiting Toxicities (DLT)s of Telisotuzumab Adizutecan	Up to Approximately 84 Days	DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications.
Part 2: Objective Response (OR) as Assessed by Blinded Independent Central Review (BICR)	Up to Approximately 33 Months	OR is defined as confirmed complete response (CR) or confirmed partial response (PR) per BICR based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Number of Participants with Adverse Events (AE)s	Up to Approximately 33 Months	An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.

Secondary Outcome Measures

Name	Time	Method
Part 2: Progression Free Survival (PFS) as Assessed by BICR	Up to Approximately 33 Months	PFS is defined as the time from the participant's randomization date to the first occurrence of radiographic progression per BICR based on RECIST v1.1 or death from any cause, whichever occurs earlier.
Part 2: Duration of Response (DOR) by BICR	Up to Approximately 33 Months	DOR is defined as the time from the first documented CR or PR per BICR to the first occurrence of radiographic progression per RECIST v1.1 or death from any cause, whichever occurs first. DOR is defined for participants with confirmed CR/PR.
Part 2: Disease Control (DC) as Assessed by BICR	Up to Approximately 33 Months	DC is defined as best overall response of confirmed CR or confirmed PR, or stable disease (SD) for at least 12 weeks following randomization date based on RECIST v1.1, as determined by the BICR.
Part 1 and Part 2: OR as Assessed by Investigator	Up to Approximately 33 Months	OR is defined as confirmed CR or confirmed PR per investigator based on RECIST v1.1.
Part 1 and Part 2: PFS as Assessed by Investigator	Up to Approximately 33 Months	PFS is defined as the time from the participant's randomization date to the first occurrence of radiographic progression per Investigator based on RECIST v1.1 or death from any cause, whichever occurs earlier.
Part 1 and Part 2: DOR as Assessed by Investigator	Up to Approximately 33 Months	DOR is defined as the time from the first documented CR or PR per investigator to the first occurrence of radiographic progression per RECIST v1.1 or death from any cause, whichever occurs first. DOR is defined for participants with confirmed CR/PR.
Part 1 and Part 2: DC as Assessed by Investigator	Up to Approximately 33 Months	DC is defined as best overall response of confirmed CR or confirmed PR, or SD for at least 12 weeks following randomization date based on RECIST v1.1, as determined by the Investigator.
Part 1 and Part 2: Overall Survival (OS)	Up to Approximately 33 Months	OS is defined as the time from participant's randomization date (Part 2) or first dose date of study treatment (Part 1) to the event of death from any cause.
Programmed Death Ligand 1 (PD-L1) Subgroups: OR	Up to Approximately 33 Months	OR is defined as confirmed CR or confirmed PR based on RECIST v1.1.
PD-L1 Subgroups: PFS	Up to Approximately 33 Months	PFS is defined as the time from the participant's randomization date to the first occurrence of radiographic progression based on RECIST v1.1 or death from any cause, whichever occurs earlier.
PD-L1 Subgroups: OS	Up to Approximately 33 Months	OS is defined as the time from participant's randomization date (Part 2) or first dose date of study treatment (Part 1) to the event of death from any cause.
PD-L1 Subgroups: DOR	Up to Approximately 33 Months	DOR is defined as the time from the first documented CR or PR to the first occurrence of radiographic progression per RECIST v1.1 or death from any cause, whichever occurs first. DOR is defined for participants with confirmed CR/PR.
PD-L1 Subgroups: DC	Up to Approximately 33 Months	DC is defined as best overall response of confirmed CR or confirmed PR, or SD for at least 12 weeks following randomization date based on RECIST v1.1.

Trial Locations

Locations (20)

Providence - St. Jude Medical Center /ID# 271414; 🇺🇸 Fullerton, California, United States

FOMAT Medical Research - Clinica mi Salud by Focil Med /ID# 274450; 🇺🇸 Oxnard, California, United States

Mid Florida Hematology And Oncology Center /ID# 273777; 🇺🇸 Orange City, Florida, United States

Astera Cancer Care /ID# 271915; 🇺🇸 East Brunswick, New Jersey, United States

New York Cancer and Blood Specialists - New York /ID# 272547; 🇺🇸 New York, New York, United States

The Mark H Zangmeister Center /ID# 272502; 🇺🇸 Columbus, Ohio, United States

Millennium Research & Clinical Development /ID# 271717; 🇺🇸 Houston, Texas, United States

Northwest Medical Specialties Tacoma /ID# 270469; 🇺🇸 Tacoma, Washington, United States

Universitaetsklinikum Koeln /ID# 268489; 🇩🇪 Koeln, Nordrhein-Westfalen, Germany

Yokohama Municipal Citizen's Hospital /ID# 271979; 🇯🇵 Yokohama-shi, Kanagawa, Japan

Kyoto University Hospital /ID# 272312; 🇯🇵 Kyoto-shi, Kyoto, Japan

National Cancer Center Hospital /ID# 273192; 🇯🇵 Chuo-Ku, Tokyo, Japan

Pan American Center for Oncology Trials /ID# 268827; 🇵🇷 Rio Piedras, Puerto Rico

Complejo Hospitalario Universitario A Coruña /ID# 271456; 🇪🇸 A Coruña, A Coruna, Spain

Hospital Universitario Virgen de la Victoria /ID# 271312; 🇪🇸 Málaga, Malaga, Spain

Hospital Universitario Virgen Macarena /ID# 271447; 🇪🇸 Seville, Sevilla, Spain

Hospital General Universitario de Alicante Doctor Balmis /ID# 271316; 🇪🇸 Alicante, Spain

Hospital Clinic de Barcelona /ID# 271452; 🇪🇸 Barcelona, Spain

Taipei Veterans General Hospital /ID# 268787; 🇨🇳 Taipei City, Taiwan

Centre Antoine-Lacassagne /ID# 268486; 🇫🇷 Nice, Provence-Alpes-Cote-d Azur, France