A Study of AP601 in Patients With Locally Unresectable Advanced or Metastatic Solid Tumors
ConditionSolid Tumours
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorAP Biosciences Inc.
About this trial
A Phase 1, Open-Label Study of the Safety, Tolerability,Pharmacokinetics, Pharmacodynamics and Clinical Activity of AP601 in Patients with Solid Tumours.The study is designed to find the highest dose of AP601 that can be given safely. Participants will be assigned to one of six cohorts. Each cohort will receive a different dose of the study medication, AP601, based on the body weight. Each cohort will initially enrol 1-3 participants. If no serious side effects are seen in the first participant(s), the next cohort will receive the next dose level.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Patients with histologically or cytologically proven locally unresectable advanced or metastatic solid tumors. Patients must be relapsed or refractory to at least one standard-of-care therapy, and/or have refused standard-of-care therapy.
Must agree not to donate sperm from signing the ICF until at aleast 90 days after the last dose of the study drug.
If engaging in sexual intercourse with a female partner who could become pregnant, must agree to use adequate contraception.
Willing and able to comply with all study assessments and adhere to the protocol schedule and restrictions.
Disqualifiers
Has received concurrent antitumor treatment or IPs within 28 days of C1D1. The antitumor treatments include chemotherapy, radiotherapy, immunotherapy, targeted therapy, hormonal therapy, or cytokine therapy.
Has received prior CD73-targeted and/or CD137-targeted therapeutics.
Has had major surgery within 28 days prior to C1D1 (excluding prior diagnostic biopsy).
Any unresolved toxicity (except alopecia) from prior therapy of ≥CTCAE Grade 1, prior to the day of the first dose of IP. Participants with Grade 2 toxicity that is not CS (e.g., alopecia, vitiligo), or that is deemed stable or irreversible (e.g., peripheral neuropathy) can be enrolled.
Trial design
Design model
Sequential
Treatments tested in this trial
AP601
DrugAP601 is a fully human bispecific antibody designed for the treatment of CD73-expressing solid tumours. Participants will receive a single infusion of AP601 once every 2 weeks (14 days) (Q2W) for up to 12 months. All doses of AP601 will be admistered intraveneously. The infusion time for all doses of AP601 in each patient will be approximately 60 to 120 minutes.
Treatment groups
36 Participants
are divided into 6 treatment groups6
Treatment groupsSee each treatment group below.
Group A: Cohort 1Experimental treatment 1 intervention
Group B: Cohort 2Experimental treatment 1 intervention
Group C: Cohort 3Experimental treatment 1 intervention
Group D: Cohort 4Experimental treatment 1 intervention
Group E: Cohort 5Experimental treatment 1 intervention
Group F: Cohort 6Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
To determine the tolerability (MTD and/or maximum administered dose [MAD] of AP601 in patients with solid tumours.
Estimate of the MTD based on DLTs observed during the DLT evaluation period.
Time frame
Initial 28 days from the first dose of AP601 which is Cycle1Day1 (each cycle is 14 days) until Cycle2Day14 (each cycle is 14 days)2
To determine the tolerability of Recommend Phase 2 Dose [RP2D])- MTD and/or maximum administered dose [MAD] of AP601 in patients with solid tumours.
RP2D is based on the safety data - Estimate of the MTD based on DLTs observed during the DLT evaluation period
Time frame
TEAEs and SAEs will be assessed at Screening until 90-day safety follow up visit.3
To determine the tolerability of Recommend Phase 2 Dose [RP2D])
RP2D tolerability is based on Pharmacokinetics data- blood samples will be collected to assess this.
Time frame
Cycle 1 - pre-dose, immediately following End of Infusion (EOI), 4 hours, 24 hours, 72 hours, 168 hours. Cycle 2- pre-dose, EOI, 4 hours, 24hours, 72hours, 168hours, Cycle 3 to Cycle 24- Predose (each cycle is 14 days), 0-6 hours, End of Trial Visit.4
To determine the tolerability of Recommend Phase 2 Dose [RP2D])
RP2D tolerability is based on Pharmacodynamics data- blood samples will be collected to assess this
Time frame
PD will be assessed Cycle 1 - pre-dose, 24 hous, 72 hours, 168 hours. Cycle 2- pre-dose, 4 hours, 24hours, 72hours, 168hours, Cycle 3 to Cycle 24- Pre-dose (each cycle is 14days) and at End of Trial Visit.Secondary outcomes
1
To assess the PK of AP601 in patients with solid tumours - Serum PK concentration of AP601.
Blood samples will be collected to assess PK.
Time frame
Cycle 1 - Pre-dose, immediately following End of Infusion (EOI), 4 hours, 24 hours, 72 hours, 168 hours. Cycle 2- pre-dose, EOI, 4 hours, 24hours, 72hours, 168hours, Cycle 3 to Cycle 24 - Predose (each cycle is 14 days), 0-6 hours and End of Trial Visit.2
To assess the PK of AP601 in patients with solid tumours - Individual maximum concentration values, directly determined from the serum concentration time profiles for each participant (Cmax)
Blood samples are collected to assess PK.
Time frame
Cycle 1 - pre-dose, immediately following End of Infusion (EOI), 4 hours, 24 hours, 72 hours, 168 hours. Cycle 2- pre-dose, EOI, 4 hours, 24hours, 72hours, 168hours, Cycle 3 to Cyle 24- Predose(each cycle is 14 days), 0-6 hours and End of Trial Visit.3
To assess the PK of AP601 in patients with solid tumours -Serum clearance following IV administration (CL)
Blood samples are collected to assess PK.
Time frame
Cycle 1 - Pre-dose, immediately following End of Infusion (EOI), 4 hours, 24 hours, 72 hours, 168 hours. Cycle 2- pre-dose, EOI, 4 hours, 24hours, 72hours, 168hours, Cycle 3 -to Cycle 24- Predose(each cycle is 14days), 0-6 hours and End of Trial Visit.4
To assess the PK of AP601 in patients with solid tumours -Area under the serum concentration-time curve (AUC) from time zero to 168 hours post-dose (AUC0-168)
Blood samples are collected to assess PK.
Time frame
Cycle 1 - Pre-dose, immediately following End of Infusion (EOI), 4 hours, 24 hours, 72 hours, 168 hours. Cycle 2- pre-dose, EOI, 4 hours, 24hours, 72hours, 168hours, Cycle 3 to Cycle 24 Predose(each cycle is 14days), 0-6 hours and End of Trial Visit.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
AP Biosciences Inc.
Lead sponsor
Avance Clinical Pty Ltd.
Collaborator
Source ClinicalTrials.gov