A Study to Evaluate the Safety, Pharmacokinetics, and Antitumor Activity of AK127 in Combination With AK104 in Advanced and Metastatic Solid Tumours

Advanced or Metastatic Solid Tumours Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05021120
• Other study ID #: AK127-101
• Status: Recruiting
• Phase: Early Phase 1
• Start date: October 12, 2021
• Est. completion date: April 7, 2025

Study information

• Verified date: March 2024
• Source: Akeso
• Contact: Baiyong Li
• Phone: +86 (0760) 8987 3999
• Email: global.trials[@]akesobio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 143
• Est. completion date: April 7, 2025
• Est. primary completion date: January 10, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced or Metastatic Solid Tumours
• Neoplasms

Intervention

Drug:
• AK127
Subjects will receive AK127 by intravenous administration
• AK104
After AK127 infusion, on the same day subjects will receive AK104 by intravenous administration

Locations

Country	Name	City	State
Australia	Ashford Cancer Centre Research	Adelaide
Australia	Austin Health	Melbourne
Australia	Monash Health	Melbourne
Australia	Southside Cancer Care Centre	Sydney
Australia	The Kinghorn Cancer Centre, St Vincents Hospital Sydney	Sydney

Sponsors (1)

Lead Sponsor	Collaborator
Akesobio Australia Pty Ltd

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and Nature of Adverse Events (AEs)	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.	From the time of informed consent signed through to 90 days after end of treatment
Primary	Number of participants with a Dose Limiting Toxicity (DLT)	DLTs will be assessed during the first treatment cycle and assessed as having a suspected relationship to study drug according to pre-specific criteria in the protocol.	Within the first six weeks of treatment
Secondary	Objective response rate (ORR)	The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR, based on RECIST Version 1.1.	Up to 2 years
Secondary	Disease control rate (DCR)	Progression-free survival is defined as the time from the start of treatment with AK127 + AK104 until the first documentation of disease progression or death due to any cause, whichever occurs first.	Up to 2 years
Secondary	Progression-free survival (PFS)	Progression-free survival is defined as the time from the start of treatment until the first documentation of disease progression or death due to any cause, whichever occurs first.	Up to 2 years
Secondary	Overall survival (OS)	Overall survival is defined as the time from the start of treatment until death due to any cause.	Up to 2 years
Secondary	Area under the curve (AUC) of AK127+AK104 for assessment of pharmacokinetics	The endpoints for assessment of PK including serum concentrations of AK127+AK104 at different timepoints after treatment administration.	From first dose of treatment through to 90 days after end of treatment
Secondary	Maximum observed concentration (Cmax) of AK127 + AK104	The endpoints for assessment of PK of AK127+AK104 include serum concentrations of AK127+AK104 at different timepoints after treatment administration.	From first dose of treatment through to 90 days after end of treatment.
Secondary	Minimum observed concentration (Cmin) of AK127+AK104	The endpoints for assessment of PK of AK127+AK104 include serum concentrations of AK127+AK104 at different timepoints after treatment administration.	From first dose of treatment through to 90 days after end of treatment
Secondary	Number of subjects who develop detectable anti-drug antibodies (ADAs)	The immunogenicity of AK127+AK104 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies (ADAs).	From first dose of treatment through to 90 days after end of treatment