A Safety and Pharmacokinetic Phase I/Ib Study of AMC303 in Patients With Solid Tumours

Sponsor

amcure GmbH (Industry)

Overall Status

Completed

CT.gov ID

NCT03009214

Collaborator

(none)

Enrollment

Locations

Arm

53.2

Duration (Months)

7.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a two part Phase I/Ib, open-label, non-randomized and multi-center, dose escalation study with a 3+3 design (Part 1) and an expansion cohort at the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) (Part 2). If MTD is not reached in Part 1, RP2D will be determined after completion of Part 1 considering safety and tolerability, also beyond the dose limiting toxicity (DLT) period, pharmacokinetic (PK) and pharmacodynamic (PD) results.

Condition or Disease	Intervention/Treatment	Phase
Malignant Solid Tumor	Drug: AMC303	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

55 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Safety, Tolerability and Pharmacokinetic Dose Escalation and Expansion, Phase I/Ib Study of AMC303 as Monotherapy in Patients With Advanced or Metastatic, Malignant Solid Tumour of Epithelial Origin

Study Start Date :

Dec 1, 2016

Actual Primary Completion Date :

Jul 28, 2020

Actual Study Completion Date :

May 7, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AMC303 cohorts will receive ascending doses of AMC303 as intravenous infusion Planned doses are: 0.1 mg/kg, 0.5 mg/kg, 1.5 mg/kg, 4 mg/kg, 10 mg/kg and 20 mg/kg	Drug: AMC303 AMC303 is a CD44v6 inhibitor blocking receptor tyrosine kinase (RTK) pathways Other Names: CD44v6 inhibitor

Arm

Intervention/Treatment

Experimental: AMC303

cohorts will receive ascending doses of AMC303 as intravenous infusion Planned doses are: 0.1 mg/kg, 0.5 mg/kg, 1.5 mg/kg, 4 mg/kg, 10 mg/kg and 20 mg/kg

Drug: AMC303

AMC303 is a CD44v6 inhibitor blocking receptor tyrosine kinase (RTK) pathways

Other Names:

CD44v6 inhibitor

Outcome Measures

Primary Outcome Measures

Safety and tolerability of AMC303 [6 months]
Number of patients with treatment-related adverse events as assessed by CTCAE v4.0

Secondary Outcome Measures

Pharmacokinetic properties of AMC303 (Cmax) [2 days]
Determine maximum plasma concentration (Cmax)
Pharmacokinetic properties of AMC303 (AUC) [2 days]
Determine systemic exposure (AUC) after intravenous infusion
Pharmacokinetic properties of AMC303 (t1/2) [2 days]
Determine half-life of AMC303 after intravenous infusion
Response rate of treatment with AMC303 in patients with metastatic solid tumors [12 months]
Determination of the complete response (CR) and partial response (PR) in patients treated with AMC303

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed and documented, advanced or metastatic, accessible malignant solid tumour of epithelial origin and for which no standard therapy exists or standard therapy has failed.
Presence of a measurable tumour according to RECIST 1.1. criteria
At least 4 weeks from the completion of any previous cytotoxic chemotherapy, 6 weeks from biological therapy (monoclonal antibodies) or cancer immunotherapy (immune checkpoint modulators) or 2 weeks from targeted therapy (receptor tyrosine kinase inhibitors) at time of administration of AMC303.
Male or female patients, at least 18 years of age
Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1
Life expectancy > 12 weeks.
Adequate haematological function defined as

Absolute neutrophil count (ANC) > 1,500 / µL
Platelets > 100,000 / µL
Haemoglobin > 9 g /dL.

Adequate renal function defined as

Glomerular filtration rate (GFR) ≥ 50 ml/min according to local laboratory standard or
Serum creatinine < 1.5 mg / dL.

Adequate hepatic function defined as

Total bilirubin < 1.5x institutional upper limit of normal (ULN)
AST, ALT ≤ 3x institutional ULN or < 5x institutional ULN if known hepatic metastases
Alkaline phosphatase < 3x institutional ULN or < 5x institutional ULN if known hepatic metastases.

Patient may have central nervous system (CNS) involvement if metastases have been treated and are stable at least 4 weeks after completion of radiation therapy and/or surgery. Stable disease is defined as absence of new neurological symptoms, absence of the need for steroid therapy and radiographic confirmation of stable disease. Radiographic confirmation of stable disease 4 weeks after completion of radiation therapy is not required unless indicated by neurological examination.
All female subjects will be considered to be of childbearing potential unless they are postmenopausal (at least 12 months consecutive amenorrhea, in the appropriate age group and without other known or suspected cause), or have been sterilized surgically. For female participants and female partners of childbearing potential, willingness and able to use two forms of highly effective contraception methods (e.g. oral contraceptive and condom, intra-uterine device and condom) while on study and for 30 days after the last study treatment. For male participants or male partners of childbearing potential, willingness and able to use two forms of highly effective contraception methods (e.g. oral contraceptive and condom, intra-uterine device and condom,) while on study and for three months after the last study treatment.
Provision of signed Informed Consent prior to any study related procedure being performed

Exclusion Criteria:

Receipt of any other investigational agent within 28 days prior to first administration of AMC303. Investigational monoclonal antibodies must not be given within 6 weeks before treatment start with AMC303.
Enrolment in another clinical study with an investigational drug
Presence of residual toxicities of CTCAE Grade > 1 after prior anti-tumour therapy within 2 weeks of first treatment with AMC303 with the exception of Grade 3 alopecia and infusion site reactions
Severe concurrent illness or psychiatric illness/social situation that would limit compliance with study requirements
Anticipation of major surgical procedures within first 4 weeks of first dose
Pregnancy or breast-feeding as determined by a serum pregnancy test (β-HCG) at screening prior to administration of AMC303 and willingness to father a child or to become pregnant
Untreated acute infectious disease
Patient is known to be suffering from Acquired Immune Deficiency Syndrome (AIDS) or is known to be HIV seropositive without AIDS defining disease
Known chronic hepatitis B or C.
History of allergic reactions attributed to compounds of similar chemical or biological composition to AMC303.
Evidence of any other medical conditions that in the opinion of the investigator may interfere with the planned treatment, affect patient compliance or place the patient at high risk from treatment-related complications
Previous malignant disease other than the target malignancy to be investigated within the last 5 years with the exception of basal or squamous carcinoma of the skin or cervical carcinoma in situ
Legal incapacity or limited legal capacity

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Jules Bordet Instiut	Brussels		Belgium	1000
2	Cliniques Universitaires Saint Luc	Brussel		Belgium	1200
3	Institut Català d'Oncologia, Hospital Duran i Reynals	L'Hospitalet de Llobregat	Barcelona	Spain	08908
4	Vall d'Hebron Institute of Oncology (VHIO)	Barcelona		Spain	08035
5	START Madrid-CIOCC, Centro Integral Oncológico Clara Campal	Madiedo		Spain	28050
6	Hospital Universitario Virgen de la Victoria	Málaga		Spain
7	Instituto de Investigación Sanitaria INCLIVA, Hospital Clínico de Valencia	Valencia		Spain	46010