Open-label, dose-escalation trial to evaluate the safety and pharmacokinetics of GEN1046 in Japanese subjects with advanced solid malignancies

JRCT ID: jRCT2031210112

Registered date:25/05/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Solid tumor
• Date of first enrollment: 06/07/2021
• Target sample size: 18
• Study type: Interventional
• Intervention(s): Acasunlimab will be administered intravenously once every 21 days. The dose levels will be determined by the starting dose and the escalation steps taken in the trial.

Outcome(s)

Primary Outcome

- Number of Participants with Dose limiting Toxicities (DLTs)
- Number of Participants with Adverse Events (AEs)
- Area under the concentration time curve (AUC) of acasunlimab
- Maximum (Peak) Plasma Concentration (Cmax) of acasunlimab
- Time to Reach Cmax (Tmax) of acasunlimab
- Plasma Trough (Pre-dose) Concentrations (Cthrough) of acasunlimab
- Elimination half-life (t 1/2) of acasunlimab

• Secondary Outcome: Number of Participants with Anti-Drug Antibody (ADA) to acasunlimab

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

- Participant must have a histologically-confirmed non-central nervous system (CNS) solid tumor that is metastatic or unresectable and for whom there is no available standard therapy likely to confer clinical benefit; or a participant who is not a candidate for such available therapy and for whom, in the opinion of the investigator, experimental therapy with acasunlimab or acasunlimab in combination with pembrolizumab may be beneficial.
- Asian race and Japanese ethnicity.
- Have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
- Have Eastern Cooperative Oncology Group (ECOG) 0-1.
- Have an acceptable hematological status.
- Have acceptable liver function.
- Have an acceptable coagulation status.
- Have acceptable renal function.
- Should provide a tumor tissue sample (formalin-fixed paraffin-embedded [FFPE] blocks/slides) from archival tissue or fresh biopsy collected before C1D1, preferably derived from advanced disease stage.

Exclude criteria

* Have uncontrolled intercurrent illness, including but not limited to:
- Ongoing or active infection requiring intravenous treatment with anti-infective therapy, or any ongoing systemic inflammatory condition requiring further diagnostic work-up or management during screening.
- Symptomatic congestive heart failure (Grade III or IV as classified by the New York Heart Association), unstable angina pectoris or cardiac arrhythmia.
- Uncontrolled hypertension defined as systolic blood pressure >= 160 mmHg and/or diastolic blood pressure >= 100 mmHg, despite optimal medical management.
- Ongoing or recent evidence of autoimmune disease.
- History of irAEs that led to prior checkpoint treatment discontinuation.
- Prior history of myositis, Guillain-Barre syndrome, or myasthenia gravis of any grade.
- History of chronic liver disease or evidence of hepatic cirrhosis.
- Evidence of interstitial lung disease.
- History of non-infectious pneumonitis that has required steroids or currently has pneumonitis.
- History of organ allograft (except for corneal transplant) or autologous or allogeneic bone marrow transplant, or stem cell rescue within 3 months prior to the first dose of trial treatment.
- Serious, non-healing wound, skin ulcer (of any grade), or bone fracture.
* Any history of intracerebral arteriovenous malformation, cerebral aneurysm, new (younger than 6 months) or progressive brain metastases or stroke.
* Prior therapy:
- Radiotherapy: Radiotherapy within 14 days prior to the first dose of trial treatment administration. Palliative radiotherapy will be allowed.
- Treatment with an anti-cancer agent (within 28 days or after at least 5 half-lives of the drug, whichever is shorter), prior to trial treatment administration.
* Toxicities from previous anti-cancer therapies that have not adequately resolved.

Related Information

• Primary Sponsor: jRCT Inquiry Receipt Center
• Secondary ID(s): NCT04937153