Clinical trial NCT05021120: A Study to Evaluate the Safety, Pharmacokinetics, and Antitumor Activity of AK127 in Combination With AK104 in Advanced and Metastatic Solid Tumours
Official title: A Phase 1a/1b, Multicenter, Open-Label, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Pharmacokinetics, and Anti-tumour Activity of AK127 in Combination With AK104 in Subjects With Advanced or Metastatic Solid Tumours
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: EARLY_PHASE1
Conditions: Advanced or Metastatic Solid Tumours
Lead sponsor: Akeso
Sponsor class: INDUSTRY
First posted: 2021-08-25
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Sequential Assignment
Primary purpose: TREATMENT

Brief summary: A Phase 1 study to evaluate the safety, tolerability, PK, immunogenicity, pharmacodynamics, and preliminary antitumor activity of AK127 in combination with AK104.

Detailed description: This is a , Phase 1, first-in-human, multicenter, open label, dose escalation and dose expansion study designed to evaluate the safety, tolerability, PK, immunogenicity, pharmacodynamics, and preliminary antitumor activity of AK127 in combination with AK104 in subjects with advanced and metastatic solid tumours. The study comprises of 2 phases: a dose escalation phase and a dose expansion phase. Dose escalation for AK127 will occur using the 3+3+3 model given with a fixed regimen of AK104. Dose expansion will open at the discretion of the Sponsor.

Eligibility criteria: Inclusion Criteria:

1. Written and signed informed consent
2. In Phase 1a, patients with relapsed or refractory advanced solid malignancies
3. In Phase 1b, patients must have received no more than three prior lines of systemic therapy
4. Subject must have at least one measurable lesion according to RECIST Version1.1.
5. Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1.
6. Available archived or fresh tumor tissue
7. Adequate organ function.
8. For dose-expansion cohorts (Phase 1b), subjects must be willing to provide two fresh biopsy samples (pre-treatment and on treatment), where clinically appropriate.
9. Females of childbearing potential and non-sterilized males who are sexually active must use an effective method of contraception from screening until 120 days after final dose of investigational product.

Exclusion Criteria:

1. History of severe hypersensitivity reactions to other mAbs.
2. Subjects with a condition requiring systemic treatment with either corticosteroid (\> 10 mg daily ) or other immunosuppressive medications within 2 weeks of study drug administration.
3. Prior use of approved or investigational anti-TIGIT, anti-PVRIG, or anti-CD96 therapy
4. Receiving any Other anticancer therapy (e.g., chemotherapy, radiotherapy, biologic or hormonal therapy for cancer treatment. etc.) within 4 weeks prior to the first dose of treatment
5. Any major surgery within 4 weeks prior to the first dose of treatment
6. Receiving agents with immunomodulatory effect within 2 weeks prior to the first dose of treatment.
7. Active or prior documented inflammatory bowel disease
8. History of organ transplant.
9. History of interstitial lung disease, noninfectious pneumonitis except for those induced by radiation therapies.
10. Known active hepatitis B or C infections or history of HIV.
11. Receipt of live attenuated vaccines within 4 weeks prior to the first dose of investigational product.
12. Patients with severe heart and lung dysfunction.

Primary outcomes:
measure: Incidence and Nature of Adverse Events (AEs)
timeFrame: From the time of informed consent signed through to 90 days after end of treatment
measure: Number of participants with a Dose Limiting Toxicity (DLT)
timeFrame: Within the first six weeks of treatment
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: Up to 2 years
measure: Disease control rate (DCR)
timeFrame: Up to 2 years
measure: Progression-free survival (PFS)
timeFrame: Up to 2 years
measure: Overall survival (OS)
timeFrame: Up to 2 years
measure: Area under the curve (AUC) of AK127+AK104 for assessment of pharmacokinetics
timeFrame: From first dose of treatment through to 90 days after end of treatment
measure: Maximum observed concentration (Cmax) of AK127 + AK104
timeFrame: From first dose of treatment through to 90 days after end of treatment.
measure: Minimum observed concentration (Cmin) of AK127+AK104
timeFrame: From first dose of treatment through to 90 days after end of treatment
measure: Number of subjects who develop detectable anti-drug antibodies (ADAs)
timeFrame: From first dose of treatment through to 90 days after end of treatment
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Ashford Cancer Centre Research
city: Melbourne
country: Australia
facility: Austin Health
city: Melbourne
country: Australia
facility: Monash Health
city: Sydney
country: Australia
facility: Southside Cancer Care Centre
city: Sydney
country: Australia
facility: The Kinghorn Cancer Centre, St Vincents Hospital Sydney
Study officials:
References: