A Study to Evaluate the Safety of INCA33890 in Participants With Advanced or Metastatic Solid Tumors

Official title

A Phase 1, Open-Label, Multicenter Study of INCA33890 in Participants With Advanced or Metastatic Solid Tumors

Overview

To evaluate the safety, tolerability, and DLTs and determine the MTD and/or RDE(s) of INCA33890 in participants with select advanced or metastatic solid tumors.

Interventions

• Drug INCA33890
  INCA33890 will be administered at protocol defined dose.
• Drug bevacizumab
  Bevacizumab will be administered at protocol defined dose.
• Drug FOLFIRI
  FOLFIRI will be administered at protocol defined dose.
• Drug FOLFOX
  FOLFOX will be administered at protocol defined dose.
• Drug Cetuximab
  Cetuximab will be administered at protocol defined dose.
• Drug ADG126
  ADG126 will be administered at protocol defined dose.

Primary outcome measures

• Dose Limiting Toxicities (DLTs) [Time frame: Up to 28 days]
• Treatment Emerging Adverse Events (TEAEs) [Time frame: Up to 2 years]
• TEAEs leading to dose modification or discontinuation [Time frame: Up to 2 years]

Secondary outcome measures (11)

• Objective response Rate [Time frame: 2 years]
• Disease Control Rate [Time frame: 2 years]
• Duration of Response [Time frame: 2 years]
• Pharmacokinetics Parameter : Cmax of INCA33890 [Time frame: Pre dose - Day 1 of Cycle 1(C1D1)- 28 (each cycle is 28 days), Day 15 of Cycle 1-3; 10min and 4hrs Post dose(PD) - C1D1,C1D4, 24hrs PD C1D2, any time PD Day 4, 8, 22, of Cycle 1, and any time during 30 day Follow Up]
• Pharmacokinetics Parameter : Tmax of INCA33890 [Time frame: Pre dose - Day 1 of Cycle 1(C1D1)- 28 (each cycle is 28 days), Day 15 of Cycle 1-3; 10min and 4hrs Post dose(PD) - C1D1,C1D4, 24hrs PD C1D2, any time PD Day 4, 8, 22, of Cycle 1, and any time during 30 day Follow Up]
• Pharmacokinetics Parameter : Cmin of INCA33890 [Time frame: Pre dose - Day 1 of Cycle 1(C1D1)- 28 (each cycle is 28 days), Day 15 of Cycle 1-3; 10min and 4hrs Post dose(PD) - C1D1,C1D4, 24hrs PD C1D2, any time PD Day 4, 8, 22, of Cycle 1, and any time during 30 day Follow Up]
• Pharmacokinetics Parameter : AUC(0-t) of INCA33890 [Time frame: Pre dose - Day 1 of Cycle 1(C1D1)- 28 (each cycle is 28 days), Day 15 of Cycle 1-3; 10min and 4hrs Post dose(PD) - C1D1,C1D4, 24hrs PD C1D2, any time PD Day 4, 8, 22, of Cycle 1, and any time during 30 day Follow Up]
• Pharmacokinetics Parameter : AUC 0-∞ of INCA33890 [Time frame: Pre dose - Day 1 of Cycle 1(C1D1)- 28 (each cycle is 28 days), Day 15 of Cycle 1-3; 10min and 4hrs Post dose(PD) - C1D1,C1D4, 24hrs PD C1D2, any time PD Day 4, 8, 22, of Cycle 1, and any time during 30 day Follow Up]
• Pharmacokinetics Parameter : CL of INCA33890 [Time frame: Pre dose - Day 1 of Cycle 1(C1D1)- 28 (each cycle is 28 days), Day 15 of Cycle 1-3; 10min and 4hrs Post dose(PD) - C1D1,C1D4, 24hrs PD C1D2, any time PD Day 4, 8, 22, of Cycle 1, and any time during 30 day Follow Up]
• Pharmacokinetics Parameter : Vz of INCA33890 [Time frame: Pre dose - Day 1 of Cycle 1(C1D1)- 28 (each cycle is 28 days), Day 15 of Cycle 1-3; 10min and 4hrs Post dose(PD) - C1D1,C1D4, 24hrs PD C1D2, any time PD Day 4, 8, 22, of Cycle 1, and any time during 30 day Follow Up]
• Pharmacokinetics Parameter : t1/2 of INCA33890 [Time frame: Pre dose - Day 1 of Cycle 1(C1D1)- 28 (each cycle is 28 days), Day 15 of Cycle 1-3; 10min and 4hrs Post dose(PD) - C1D1,C1D4, 24hrs PD C1D2, any time PD Day 4, 8, 22, of Cycle 1, and any time during 30 day Follow Up]

Eligibility criteria

Inclusion criteria

• ≥18 years old
• Histologically or cytologically confirmed advanced or metastatic malignancies as defined in the protocol.
• Part 1: Participants must have experienced disease progression after treatment with, be intolerant to, or be ineligible for, or refused available therapies, including anti-PD-(L)1 or anti-CTLA4 therapy if applicable, that are known to confer clinical benefit. Part 2: depending on cohort, participants may have received or not prior treatment for the malignancy under study.
• ECOG performance status score of 0 or 1.
• Willingness to undergo pre- and on-treatment tumor biopsy (core or excisional). Biopsies are mandatory depending on the cohorts.
• Presence of measurable disease according to RECIST v1.1.

Exclusion criteria

• Any known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years.
• Not recovered to ≤ Grade 1 or baseline from residual toxicities of prior therapy.
• Has active autoimmune disease requiring systemic immunosuppression with corticosteroids.
• Brain or CNS metastases untreated or that have progressed.
• History of organ transplant, including allogeneic stem cell transplantation.
• History of clinically significant or uncontrolled cardiac disease.
• Active HBV, active HCV, or HIV positive.
• Is on chronic systemic steroids (> 10 mg/day of prednisone or equivalent).
• Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment
• Participants that have been initiated on or had modifications in anticoagulation therapies within the last 3 months prior to first dose of treatment.
• Significant concurrent, uncontrolled medical condition, eg:

• Cardiovascular: Participants with known vasculitis, aneurisms, and other vascular malformations of clinical significance or history of myocarditis.
• Gastrointestinal: Any bowel obstruction within 60 days prior to C1D1.
• Participants with adequate laboratory values within the protocol defined ranges.

Other protocol-defined Inclusion/Exclusion Criteria may apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 11 centers

• The Angeles Clinic and Research Institute — Los Angeles
• Valkyrie Clinical Trials — Los Angeles
• Dana Farber Cancer Institute — Boston
• Cancer and Hematology Centers of Western Michigan-Start Midwest — Grand Rapids
• Hackensack University Medical Center — Hackensack
• Nyu Langone Health - Long Island Hospital — Mineola
• Laura and Isaac Perlmutter Cancer Center — New York
• University of Pennsylvania — Philadelphia
• … and 3 more centers

Spain · 5 centers

• Start Barcelona — Barcelona
• Hospital General Universitario Vall D Hebron — Barcelona
• Fundacion Jimenez Diaz University Hospital — Madrid
• Hospital Universitario 12 de Octubre — Madrid
• Centro Integral Oncologico Clara Campal — Madrid

United Kingdom · 5 centers

• Cambridge University Hospitals Nhs Foundation Trust — Cambridge
• Guys and St Thomas Nhs Foundation Trust — London
• Imperial College Healthcare Nhs Trust - Hammersmith Hospital — London
• The Christie Nhs Foundation Trust Uk — Manchester
• Freeman Hospital Newcastle Upon Tyne Foundation Nhs Trust — Newcastle upon Tyne

Denmark · 4 centers

• Rigshospitalet Uni of Hospital of Copenhagen — Copenhagen
• Herlev Og Gentofte Hospital — Herlev
• Odense University Hospital — Odense C
• Vejle Hospital — Vejle

China · 3 centers

• Cancer Hospital Chinese Academy of Medical Sciences — Beijing
• Peking University People'S Hospital — Beijing
• The First Affiliated Hospital, Zhejiang University School of Medicine (Fahzu) — Hangzhou

Italy · 3 centers

• Fondazione Irccs Istituto Nazionale Dei Tumori — Milan
• Irccs Istituto Clinico Humanitas — Rozzano
• Centro Ricerche Cliniche Di Verona — Verona

Japan · 3 centers

• Kansai Medical University Hospital — Hirakata
• National Cancer Center Hospital — Tokyo
• The Cancer Institute Hospital of Jfcr — Tokyo

Switzerland · 3 centers

• Istituto Oncologico Della Svizzera Italiana — Bellinzona
• Centre Hospitalier Universitaire Vaudois (Chuv) — Lausanne
• Kantonsspital St. Gallen — Sankt Gallen

France · 2 centers

• Centre Leon Berard — Lyon
• Institut Gustave Roussy — Villejuif

Identifiers

NCT: NCT05836324 · INCA 33890-101 · 2022-502456-31-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗