A Multicenter, Phase 1, Dose Escalation and Dose Expansion Study to Evaluate the Safety, Pharmacokinetics, and Antitumor Activity of AK117 in Subjects With Advanced Solid Tumors or Lymphomas
Overview
- Phase
- Phase 1
- Intervention
- AK117
- Conditions
- Neoplasms Malignant
- Sponsor
- Akeso
- Enrollment
- 49
- Locations
- 1
- Primary Endpoint
- Number of participants with adverse events (AEs)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is a multicenter, open label, single arm, Phase 1，dose escalation and dose expansion study designed to evaluate the safety, tolerability, pharmacodynamics, PK, immunogenicity, and preliminary antitumor activity of AK117 administered intravenously to adult subjects with relapsed/refractory advanced or metastatic solid tumors or lymphomas.
Detailed Description
The study comprises a dose escalation phase and a dose expansion phase. The phases will be conducted sequentially. Approximately 162 subjects will be enrolled in this study.
Investigators
Eligibility Criteria
Inclusion Criteria
- •All Subjects
- •Able to provide written and signed informed consent and any locally required authorization obtained from the subject/legal representative, which must be obtained prior to performing any protocol related procedures.
- •Men or women aged ≥18 years and ≤75 at the time of study entry.
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or
- •Life expectancy ≥12 weeks.
- •Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures as specified in the protocol.
- •Subjects must provide the tumor tissue samples after the diagnosis of solid tumor or lymphoma.
- •Adequate organ function.
- •Subjects with Solid Tumors：Subjects must have a histologically or cytologically confirmed advanced solid tumor that is refractory or relapsed to the current standard therapies, or for which no effective standard therapy is available. Subject must have at least 1 measurable lesion according to RECIST v1.
- •Subjects with Lymphomas：Subjects must have histologically confirmed non-Hodgkin lymphoma(NHL), which may include transformed lymphoma, relapsed or refractory to autologous hematopoietic stem cell transplantation, or at least 2 lines of prior chemotherapy. Subjects must have disease that is measurable or assessable for response as per Lugano Classification 2014.
Exclusion Criteria
- •All Subjects
- •Concurrent enrollment in another clinical study, unless it is an observational clinical study or the follow up period of an interventional study.
- •Prior malignancy active within the previous 3 years except for the tumor for which a subject is enrolled in the study, and locally curable cancers that have been apparently cured.
- •Receipt: The last cycle of anticancer therapy within 3 weeks prior to the first dose of investigational product; Anticancer small molecule targeted agent, palliative local treatment for non-target lesions, non-specific immunomodulatory therapy within 2 weeks prior to the first dose of investigational product; Chinese medicines with anti-tumor indications within 1 week prior to the first dose of investigational product; Any major surgery within 4 weeks; RBC infusion within 3 months.
- •Metastasis or infiltration of brainstem and meninges;Metastasis or compression of the spinal cord; Active brain/central nervous system (CNS) metastases.
- •Subjects with clinical symptoms or repeated drainage of pleural effusion, pericardial effusion or ascites.
- •Cancer invasion of important surrounding organs or risk of esophageal tracheal fistula or esophageal pleural fistula.
- •Known history of testing positive for human immunodeficiency virus (HIV) or known active acquired immunodeficiency syndrome.
- •Known active hepatitis B or C infections (known positive HBsAg result or positive HCV antibody with detectable HCV ribonucleic acid \[RNA\] results).
- •Active or prior documented autoimmune disease that may relapse.
Arms & Interventions
AK117 monotherapy
AK117 monotherapy intravenous (IV) infusion - Weekly doses
Intervention: AK117
Outcomes
Primary Outcomes
Number of participants with adverse events (AEs)
Time Frame: From the time of informed consent signed through 30 days after the last dose of AK117
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Number of participants with a Dose Limiting Toxicity (DLT)
Time Frame: During the first 21 days
DLTs will be assessed during the first 21 days of treatment for dose-escalation phase and are defined as toxicities that meet pre-defined severity criteria, and assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications .
Secondary Outcomes
- Disease control rate (DCR)(Up to 2 years)
- Maximum observed concentration (Cmax) of AK117(From first dose of AK117 through to 30 days after last dose of AK117)
- Objective response rate (ORR)(Up to 2 years)
- Minimum observed concentration (Cmin) of AK117 at steady state(From first dose of AK117 through to 30 days after last dose of AK117)
- Number of subjects who develop detectable anti-drug antibodies (ADAs)(From first dose of AK117 through to 30 days after last dose of AK117)