A study to test whether different combinations of BI 765063, ezabenlimab, chemotherapy, cetuximab, and BI 836880 help people with head and neck cancer or liver cancer

JRCT ID: jRCT2031210650

Registered date:08/03/2022

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) or hepatocellular c
• Date of first enrollment: 25/02/2022
• Target sample size: 150
• Countries of recruitment: Belgium,Japan,Chilie,Japan,France,Japan,Gerymany,Japan,Georgia,Japan,Italy,Japan,Malaysia,Japan,Mexico,Japan,Poland,Japan,Portugal,Japan,Russian Federation,Japan,Slovakia,Japan,Spain,Japan,Sweden,Japan,Thailand,Japan,Ukraine,Japan,United Kingdom,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

Intravenous (IV)
Ezabenlimab: 240 mg once every three weeks (q3w)
BI 836880: 720 mg q3w
BI 765063: 24 mg/kg q3w
Dosed on Day 1 of each 21-day cycle.
Cetuximab:
400 mg/m2 initial dose followed by 250 mg/m2 weekly
or
500 mg/m2 administered every 2 weeks
Paclitaxel: 80 mg/m2 weekly
Docetaxel: 75 mg/m2 every 3 weeks
or
30 mg/m2 weekly, may be increased to 40 mg/m2 if tolerated as per local practice
5-fluorouracil: 1,000 mg/m2/day for 4 days every 3 weeks
Methotrexate: 40 mg/m2 weekly, may be increased to 60 mg/m2 if tolerated as per local practices

Oral (tablet):
Capecitabine: 1250 mg/m2 twice daily orally for 2 weeks followed by a one week rest period in 3-week cycles

Outcome(s)

• Primary Outcome: Objective response (OR) with confirmation, defined as the best overall response of complete response (CR) or partial response (PR), where best overall response is determined according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1(v1.1) by investigators assessment from first treatment administration until the earliest of disease progression, death, or last evaluable tumour assessment before start of subsequent anti-cancer therapy, loss to follow-up, or withdrawal of consent.

Secondary Outcome

Duration of objective response (DOR), defined as the time from first documented CR or PR (RECIST v1.1) until the earliest sign of disease progression or death among patients with OR.
Disease control (CR, PR, or stable disease) according to RECIST v1.1 as assessed by the Investigator.
Progression-free survival (PFS), which is defined as the duration from the date of first treatment to the date of progressive disease (PD) or death.
Occurrence of treatment emergent adverse events (AEs) by investigators assessment from first treatment administration until the earliest of death, subsequent anti-cancer therapy, lost to follow-up or withdrawal of consent.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Patients homozygous for V1 allele (including V1-like alleles) of SIRPa
Patients with at least one measurable lesion as per RECIST v1.1
Eastern Cooperative Oncology Group (ECOG) performance status <=1
For patients with HNSCC only (Cohorts A and B)
Patients with recurrent or metastatic histologically or cytologically confirmed HNSCC of the oral cavity, oropharynx, hypopharynx, and larynx which is considered incurable by local therapies (e.g. surgery, radiotherapy).
Immune checkpoint inhibitor naive patients who progressed on a standard platinum-based therapy in the recurrent/metastatic setting.
For patients with HCC only (Cohorts C, D, and E)
Patients with locally advanced/metastatic and/or unresectable HCC as confirmed histologically or by diagnostic imaging (dynamic Computed Tomography CT or Magnetic Resonance Imaging MRI) according to AASLD criteria
60 patients who have not received prior systemic therapy will be randomized in 2 1st line HCC.
30 patients who have progressed on 1st line atezolizumab+bevacizumab therapy/regimen will be included in a 2nd line HCC.
Child-Pugh Score of A.

Exclude criteria

Patients with at least one SIRPa V2 allele, i.e. SIRPa V1/V2 or V2/V2 individuals.
Previous treatment with any anti-PD-(L)1, anti-SIRPa, or anti-VEGF (for cohorts using BI 836880 only), except for patients treated in 2nd line HCC cohort where previous treatment with atezolizumab+bevacizumab is required.
For patients with HNSCC only (Cohorts A and B )
Patients with nasopharyngeal carcinoma.
For patients with HCC only (Cohorts C, D and E)
Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
Tumour of diffuse infiltrative HCC type (hypovascular infiltrative tumours with ill-defined borders).
Clinically meaningful ascites, defined as ascites requiring non-pharmacologic intervention (e.g. paracentesis) to maintain symptomatic control, within 6 months prior to the first scheduled dose.
History of recent bleeding disorders or risk of bleeding (including history of fistulae, GI perforation, or intra-abdominal abscess) within 6 months of initiation of study treatment.
Patients with untreated or incompletely treated varices with bleeding or high-risk for bleeding

Related Information

• Primary Sponsor: Tsunoda Toru
• Secondary ID(s): NCT05249426