Clinical trial NCT04958239: A Study to Test BI 765179 Alone and in Combination With Ezabenlimab in Patients With Advanced Cancer (Solid Tumors) and BI 765179 in Combination With Pembrolizumab in Patients With Advanced Head and Neck Cancer
Official title: An Open Label, Phase I Dose-finding and Expansion Study of BI 765179 as Monotherapy and in Combination With Ezabenlimab (BI 754091) in Patients With Advanced Solid Cancers, and BI 765179 in Combination With Pembrolizumab in First-line PD-L1-positive Metastatic or Incurable, Recurrent Head and Neck Squamous Cell Carcinoma (HNSCC)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Neoplasms
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2021-07-12
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study is open to adults with advanced cancer (solid tumors) and people with advanced head and neck cancer. The study has 2 parts. The purpose of Part 1 of this study is to find the highest dose of a medicine called BI 765179 that people with solid tumors can tolerate when taken alone or together with a medicine called ezabenlimab. The goal of Part 2 is to find out whether BI 765179 in combination with a medicine called pembrolizumab helps people with advanced head and neck cancer.

In Part 1, each participant is put into 1 of 2 groups. Participants get BI 765179 alone or in combination with ezabenlimab as infusion into a vein every 3 weeks. In Part 2, participants are also divided into 2 groups. 1 group gets a low dose of BI 765179 in combination with pembrolizumab and the other group gets a high dose of BI 765179 in combination with pembrolizumab. Participants receive the study treatment as infusions into a vein.

BI 765179, ezabenlimab, and pembrolizumab are antibodies that may help the immune system fight cancer. In this study, BI 765179 is given to people for the first time.

Participants can stay in the study up to 3 years (Part 1) or 2 years (Part 2) if they benefit from treatment and can tolerate it. The doctors regularly check the participants' health and note any health problems that could have been caused by the study treatment.


Eligibility criteria: Inclusion Criteria:

All cohorts:

* Patients with locally advanced, unresectable or metastatic solid tumors who are either refractory after standard therapy for the disease or for whom standard therapy is not appropriate
* Tumor with expected high expression of Fibroblast activation protein (FAP) of the following histologies:

  * Non-small cell lung carcinoma (NSCLC)
  * Gastric cancer
  * Esophageal adenocarcinoma or squamous cell carcinoma
  * Urothelial bladder carcinoma
  * Head and neck squamous cell carcinoma
  * Cutaneous malignant melanoma
  * Cutaneous squamous cell carcinoma
  * Hepatocellular carcinoma
  * Pancreatic adenocarcinoma
  * Colorectal cancer
  * Malignant pleural mesothelioma
  * Cervical squamous cell cancer
  * Ovarian carcinoma
  * Triple-negative breast cancer
* At least 18 years of age at the time of the consent or over the legal age of consent in countries where that is greater than 18 years
* Signed and dated, written informed consent (IC) in accordance with ICH-GCP and local legislation prior to admission to the trial
* At least one measurable lesion outside of central nervous system (CNS) as defined per modified Response evaluation criteria in solid tumors (RECIST) v1.1
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Adequate liver, bone marrow and renal organ function
* Male or female patients. Women of childbearing potential (WOCBP) and men able to father a child must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. These methods must be used during the study and for at least 6 months after the last dose of the study medication. A list of contraception methods meeting these criteria is provided in the patient information.
* Patients with brain metastases are eligible provided they meet all of the following criteria:

  * Brain metastases have adequately been treated and are considered stable by the Investigator
  * Radiotherapy or surgery for brain metastases was completed at least 2 weeks prior to the first administration of BI 765179
  * Patient is off steroids for at least 7 days (physiologic doses of steroids is permitted, if this was stable for the last 4 weeks)
  * The patient is off anti-epileptic drugs for at least 7 days

Back-fill cohorts only:

* Patient has agreed to and signed an IC form to provide mandatory pre-treatment and on-treatment fresh tumor biopsy
* At least one lesion (separate from the evaluable target lesion outside of the CNS as defined per RECIST v1.1) that is accessible for mandatory paired pre and on-treatment biopsy

Phase 1b:

* Histologically or cytologically confirmed diagnosis of metastatic or incurable, recurrent head and neck squamous cell carcinoma (HNSCC)
* No prior systemic therapy administered in the metastatic or incurable, recurrent setting
* Primary tumor locations of oropharynx, oral cavity, hypopharynx, or larynx
* At least 18 years of age at the time of the consent or over the legal age of consent in countries where that is greater than 18 years
* Signed and dated written IC in accordance with ICH-GCP and local legislation prior to admission to the trial Further inclusion criteria apply

Exclusion Criteria:

Phase 1a

* Currently enrolled in another investigational device or drug trial
* Previous or concomitant malignancies other than the one treated in this trial within the last 2 years except:

  * Effectively treated non-melanoma skin cancers
  * Effectively treated carcinoma in situ of the cervix
  * Effectively treated ductal carcinoma in situ
  * Other effectively treated malignancy that is considered cured by 'local treatment'
* Previous treatment with agents targeting CD137
* Known leptomeningeal disease or spinal cord compression due to disease
* Anticoagulant treatment that cannot be safely interrupted if medically needed (e.g., biopsy) based on the opinion of the Investigator
* Persistent toxicity from previous treatments that has not resolved to ≤ Common terminology criteria for adverse events (CTCAE) Grade 1 (except for alopecia, CTCAE Grade 2 neuropathy, asthenia/fatigue or grade 2 endocrinopathies controlled by replacement therapy)
* Patient has a diagnosis of immunodeficiency
* Patient with history of immunosuppressive medication within 14 days prior to the first dose of BI 765179. The following are exceptions to this criterion:

  * Use of intranasal, inhaled, or topical corticosteroids, local steroid injections (e.g., intra-articular injections)
  * Systemic corticosteroids at physiologic doses ≤10 mg/day (prednisone or equivalent)
  * Physiological replacement dose of corticosteroids Further exclusion criteria apply.

Phase Ib

* Disease suitable for local therapy administered with curative intent
* Participants must not have a primary tumor site of nasopharynx or sino-nasal cancer or salivary gland cancers (any histology)
* Currently enrolled in another investigational device or drug trial
* Life expectancy of \<3 months and/or has rapidly progressing disease
* Diagnosed and/or treated additional malignancy within 2 years prior to randomization with the exception of curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or curatively resected in situ cervical and/or in situ breast cancers Further exclusion criteria apply

Primary outcomes:
measure: Phase 1a: Maximum Tolerated Dose (MTD)
timeFrame: Up to Day 21 (end of Cycle 1)
measure: Phase 1a: Occurrence of Dose Limiting Toxicities (DLTs) in the MTD evaluation period
timeFrame: Up to Day 21 (end of Cycle 1)
measure: Phase 1b: Objective response (OR)
timeFrame: Up to 2 years.
Secondary outcomes:
measure: Phase 1a: Occurrence of DLTs during the on-treatment period (per arm)
timeFrame: up to 36 months
measure: Phase 1a: Maximum measured concentration of BI 765179 in plasma (Cmax)
timeFrame: Up to Day 21 (end of Cycle 1)
measure: Phase 1a: Area under the concentration-time curve of BI 765179 in plasma over a uniform dosing interval from zero to 504h (AUC0-504)
timeFrame: Up to Day 21 (end of Cycle 1)
measure: Phase Ib: Occurrence of adverse events (AEs) using the US National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5
timeFrame: Up to 2 years.
measure: Phase 1b: Occurrence of serious AEs (SAEs) during the on-treatment period
timeFrame: Up to 2 years.
measure: Phase 1b: OR assessed by the Investigator according to immune-related RECIST (iRECIST)
timeFrame: Up to 2 years.
measure: Phase Ib: Duration of response (DoR) assessed by RECIST v1.1
timeFrame: Up to 2 years.
measure: Phase 1b: DoR assessed by iRECIST
timeFrame: Up to 2 years.
measure: Phase 1b: Progression-free survival (PFS) in all patients assessed by the Investigator according to RECIST v1.1
timeFrame: Up to 2 years.
measure: Phase 1b: PFS in all patients assessed by the Investigator according to iRECIST
timeFrame: Up to 2 years.
measure: Phase 1b: PFS rate at 14 weeks
timeFrame: Up to 2 years.
measure: Phase 1b: Overall survival (OS)
timeFrame: Up to 2 years.
measure: Phase 1b: OS rate at 12 months
timeFrame: Up to 2 years.
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Beverly Hills
country: United States
facility: Beverly Hills Cancer Center
state: California
city: Chapel Hill
country: United States
facility: The University of North Carolina at Chapel Hill
state: North Carolina
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: San Antonio
country: United States
facility: NEXT Oncology-San Antonio-65273
state: Texas
city: Albury
country: Australia
facility: Border Cancer Hospital
state: New South Wales
city: Darlinghurst
country: Australia
facility: Kinghorn Cancer Centre
state: New South Wales
city: Douglas
country: Australia
facility: Townsville Hospital
state: Queensland
city: Heidelberg
country: Australia
facility: Austin Hospital
state: Victoria
city: Bruxelles
country: Belgium
facility: Brussels - UNIV Saint-Luc
city: Edegem
country: Belgium
facility: Edegem - UNIV UZ Antwerpen
city: Kortrijk
country: Belgium
facility: Kortrijk - HOSP AZ Groeninge Kennedylaan
city: Sao Paulo
country: Brazil
facility: ICESP - Instituto do Cancer do Estado de Sao Paulo
city: Sao Paulo
country: Brazil
facility: Beneficência Portuguesa - Real e Benemérita Associação Portuguesa de Beneficência
city: São Paulo
country: Brazil
facility: Hospital Sírio Libanês-São Paulo-68088
city: Bengbu
country: China
facility: The First Affiliated Hospital Of Bengbu Medical College
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
city: Shanghai
country: China
facility: Shanghai East Hospital
city: Wuhan
country: China
facility: Wuhan Union Hospital
city: Brno
country: Czechia
facility: Masaryk Memorial Cancer Institute
city: Bordeaux
country: France
facility: HOP Saint-André
city: Dijon
country: France
facility: CTR Georges-François Leclerc
city: Saint-Herblain
country: France
facility: INS Cancérologie Ouest Saint-Herblain
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg
city: Halle (Saale)
country: Germany
facility: Martin-Luther-Universität Halle-Wittenberg
city: Stuttgart
country: Germany
facility: Klinikum Stuttgart
city: Jerusalem
country: Israel
facility: Shaare-Zedek Medical Center, Oncology Institute
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center
city: Napoli
country: Italy
facility: Istituto Nazionale IRCCS Tumori Fondazione Pascale
city: Aichi, Nagoya
country: Japan
facility: Aichi Cancer Center Hospital
city: Chiba, Kashiwa
country: Japan
facility: National Cancer Center Hospital East
city: Kanagawa, Yokohama
country: Japan
facility: Kanagawa Cancer Center
city: Osaka, Osaka
country: Japan
facility: Osaka International Cancer Institute
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seongnam
country: Korea, Republic of
facility: CHA Bundang Medical Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Ciudad de Mexico
country: Mexico
facility: Centro Oncologico Internacional
city: Ciudad de Mexico
country: Mexico
facility: ARKE SMO S.A. de C.V
city: Mexico
country: Mexico
facility: Instituto Nacional de Cancerologia
city: Monterrey
country: Mexico
facility: Hospital Universitario Dr Jose Eleuterio Gonzalez
city: Zapopan
country: Mexico
facility: Investigacion Biomedica para el Desarrollo de Farmacos, S.A. de C.V.
city: Amsterdam
country: Netherlands
facility: VU University Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum-ROTTERDAM-50697
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra
Study officials:
References: