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

NCT03009214 | Completed Phase 1 DMC

• 1 other identifier: AMC303-01
• Study Type: interventional
• Target: 55
• Locations: 2 countries
• Sites: 7

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.

Conditions

Malignant Solid Tumor

Keywords

solid epithelial cancer; CD44v6; c-Met; VEGFR-2; RON; receptor tyrosine kinase

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of AMC303

  Number of patients with treatment-related adverse events as assessed by CTCAE v4.0

  6 months

Secondary Outcomes (4)

• Pharmacokinetic properties of AMC303 (Cmax)

  2 days

• Pharmacokinetic properties of AMC303 (AUC)

  2 days

• Pharmacokinetic properties of AMC303 (t1/2)

  2 days

• Response rate of treatment with AMC303 in patients with metastatic solid tumors

  12 months

Study Arms (1)

AMC303

EXPERIMENTAL

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

Interventions

AMC303 DRUG

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

Also known as: CD44v6 inhibitor

AMC303

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• amcure GmbH: lead

Study Sites (7)

Jules Bordet Instiut

Brussels, 1000, Belgium

Location

Cliniques Universitaires Saint Luc

Brussels, 1200, Belgium

Location

Institut Català d'Oncologia, Hospital Duran i Reynals

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Vall d'Hebron Institute of Oncology (VHIO)

Barcelona, 08035, Spain

Location

START Madrid-CIOCC, Centro Integral Oncológico Clara Campal

Madiedo, 28050, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, Spain

Location

Instituto de Investigación Sanitaria INCLIVA, Hospital Clínico de Valencia

Valencia, 46010, Spain

Location

Related Publications (1)

• Matzke-Ogi A, Jannasch K, Shatirishvili M, Fuchs B, Chiblak S, Morton J, Tawk B, Lindner T, Sansom O, Alves F, Warth A, Schwager C, Mier W, Kleeff J, Ponta H, Abdollahi A, Orian-Rousseau V. Inhibition of Tumor Growth and Metastasis in Pancreatic Cancer Models by Interference With CD44v6 Signaling. Gastroenterology. 2016 Feb;150(2):513-25.e10. doi: 10.1053/j.gastro.2015.10.020. Epub 2015 Oct 24.

  PMID: 26597578 BACKGROUND

Related Links

• Homepage amcure

Study Officials

• Klaus Dembowsky, MD PhD

  amcure GmbH

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2016
• First Posted: January 4, 2017
• Study Start: December 1, 2016
• Primary Completion: July 28, 2020
• Study Completion: May 7, 2021
• Last Updated: May 10, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

ES (5); BE (2)