PCA062 in pCAD-positive Tumors.

A Phase 1 Multi-center, Open-label Dose Escalation and Expansion Study of PCA062 Administered Intravenously in Adult Patients With p-CAD Positive Tumors

A first-in-human sttudy using PCA062 in patients with p-CAD positive solid tumors.

Study Overview

• Status: Completed
• Conditions: Esophageal Cancer; Triple Negative Breast Cancer; Head & Neck Cancer
• Intervention / Treatment: Drug: PCA062

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Villejuif Cedex, France, 94805
    • Novartis Investigative Site
• Italy
  • MI
    • Milano, MI, Italy, 20133
      • Novartis Investigative Site
• Japan
  • Tokyo
    • Koto ku, Tokyo, Japan, 135 8550
      • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 169610
    • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28009
    • Novartis Investigative Site
• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Novartis Investigative Site
    • San Antonio, Texas, United States, 78229
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. Male or female ≥ 18 years of age
2. Documented pCAD expressing tumor cells with the exception of HNSCC and ESCC. An archived tumor sample collected within 36 months prior to baseline if available, or a new tumor biopsy sample must be available for molecular pre-screening.
3. Consent for a tumor biopsy at screening
4. Progressive disease and no effective therapy exists
5. Measurable disease as per RECIST v1.1 criteria
6. ECOG Performance status of ≤ 2

Exclusion criteria:

1. CNS metastatic involvement
2. Clinically significant cardiac, respiratory, gastrointestinal, renal, hepatic or neurological conditions.
3. A history of serious allergic reactions, which in the opinion of the investigator pose an increased risk of serious infusion reactions.
4. Monocular vision or has media opacities or any other condition that precludes monitoring of the retina or the fundus, or has a history of ophthalmology exam with retina or cornea abnormalities
5. Previously treated with anti-pCAD biologic therapies.

6. Received anti-cancer therapies within the following time frames prior to the first dose of study treatment:

   • Conventional cytotoxic chemotherapy: ≤4 weeks
   • Biologic therapy (eg, antibodies), other than ADCs: ≤4 weeks
   • Non-cytotoxic small molecule therapeutics: ≤5 T1/2 or ≤2 weeks (whichever is longer)
   • Other investigational agents: ≤4 weeks
   • Radiation therapy (palliative setting is allowed.): ≤4 weeks
   • Major surgery: ≤2 weeks

7. Patient has out of range laboratory values defined as:

   • Hematological values:
   • Absolute neutrophil count (ANC) <1.5 x 109/L
   • Hemoglobin (Hgb) <9 g/dL
   • Platelets <100 x 109/L
   • Hepatic and renal function
   • Total bilirubin >1.5 x upper limit of normal (ULN). For patients with Gilbert's syndrome, total bilirubin >2.5 x ULN.
   • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 x ULN for patients without tumor involvement of the liver or >5 x ULN for patients with tumor involvement of the liver.
   • Serum creatinine >1.5 x ULN and/or measured creatinine clearance < 40 ml/min

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Esophageal Cancer	Drug: PCA062
Experimental: Triple Negative Breast Cancer	Drug: PCA062
Experimental: Head and Neck Cancer	Drug: PCA062

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence rate of dose limiting toxicities	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of serious/adverse events		Duration of study (each treatment cycle = 14 days)
Pharmacokinetic parameter Cmax	Cmax = the maximum concentration (peak) of the drug observed in the blood after a single administration of the drug	84 days
Presence of PCA062 anti-bodies	The presence and/or concentration of the anti-bodies will be tested from the blood samples collected	84 days
Overall response rate		Duration of study (each treatment cycle = 14 days)
Duration of response		Duration of study (each treatment cycle = 14 days)
Progression free survival		18 months
Disease control rate		18 months
Best overall response		Duration of study (each treatment cycle = 14 days)
Pharmacokinetic paramater Tmax	Tmax = the time the drug takes to reach maximum (peak) concentration in the blood	84 days

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Duca M, Lim DW, Subbiah V, Takahashi S, Sarantopoulos J, Varga A, D'Alessio JA, Abrams T, Sheng Q, Tan EY, Rosa MS, Gonzalez-Maffe J, Sand-Dejmek J, Fabre C, Martin M. A First-in-Human, Phase I, Multicenter, Open-Label, Dose-Escalation Study of PCA062: An Antibody-Drug Conjugate Targeting P-Cadherin, in Patients With Solid Tumors. Mol Cancer Ther. 2022 Apr 1;21(4):625-634. doi: 10.1158/1535-7163.MCT-21-0652.

Helpful Links

• Results for CPCA062X2101 can be found on the Novartis Clinical Trial Results Website

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2015
• Primary Completion (Actual): July 17, 2018
• Study Completion (Actual): July 17, 2018

Study Registration Dates

• First Submitted: February 9, 2015
• First Submitted That Met QC Criteria: February 24, 2015
• First Posted (Estimate): March 3, 2015

Study Record Updates

• Last Update Posted (Actual): December 19, 2020
• Last Update Submitted That Met QC Criteria: December 16, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Triple Negative Breast Cancer; Esophageal Cancer; Head & Neck Cancer; PCA062; pCAD, pcadherin, solid-tumors
• Additional Relevant MeSH Terms: Digestive System Diseases; Skin Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Breast Diseases; Esophageal Diseases; Breast Neoplasms; Head and Neck Neoplasms; Triple Negative Breast Neoplasms; Esophageal Neoplasms
• Other Study ID Numbers: CPCA062X2101; 2014-003732-40 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No