Safety and Efficacy of KY1044 and Atezolizumab in Advanced Cancer

A Phase 1/2, Open-label, Multi-center Study of the Safety and Efficacy of KY1044 as Single Agent and in Combination With Anti-PD-L1 (Atezolizumab) in Adult Patients With Selected Advanced Malignancies

A Phase 1/2, open label, multi-center study to evaluate the safety, efficacy and tolerability of KY1044 as single agent and in combination with anti-PD-L1 (atezolizumab) in adult patients with selected advanced malignancies, who are ineligible for or there are no available therapies known to confer a clinical benefit for their disease, or they have exhausted all such available options in each indication and therefore will be patients for whom a clinical trial is appropriate.

Study Overview

• Status: Active, not recruiting
• Conditions: Melanoma; Renal Cell Carcinoma; Cervical Cancer; Hepatocellular Carcinoma; Gastric Cancer; Pancreatic Cancer; Esophageal Cancer; Metastatic Cancer; Squamous Cell Carcinoma of Head and Neck; Triple Negative Breast Cancer; Non-small Cell Lung Cancer; Advanced Cancer
• Intervention / Treatment: Drug: KY1044; Drug: KY1044 and atezolizumab

• Study Type: Interventional
• Enrollment (Estimated): 280
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Trial Transparency Email Recommended; Phone Number: Option 6 1-800-633-1610; Email: contact-US@sanofi.com

Study Locations

• Hungary
  • Budapest, Hungary, 1122
    • Kymab investigational site 3602
  • Szabolcs-Szatmár-Bereg
    • Nyíregyháza, Szabolcs-Szatmár-Bereg, Hungary, 4400
      • Kymab investigational site 3601
• Italy
  • Milano, Italy
    • Kymab investigational site 3901
  • Milano, Italy
    • Kymab investigational site 3903
  • Napoli, Italy
    • Kymab investigational site 3902
  • Roma, Italy
    • Kymab investigational site 3910
  • Turin, Italy, 10128
    • Kymab investigational site 3908
  • Forlì-Cesena
    • Meldola, Forlì-Cesena, Italy, 47014
      • Kymab investigational site 3904
  • Torino
    • Candiolo, Torino, Italy, 10060
      • Kymab investigational site 3906
• Poland
  • Mazowieckie
    • Siedlce, Mazowieckie, Poland, 04-141
      • Kymab investigational site 4801
• Taiwan
  • Taipei, Taiwan
    • Kymab investigational site 8801
  • Changhwa
    • Changhua City, Changhwa, Taiwan, 505
      • Kymab investigational site 8806
• United Kingdom
  • London, United Kingdom
    • Kymab investigational site 4405
  • Manchester, United Kingdom
    • Kymab investigational site 4402
  • Oxford, United Kingdom
    • Kymab investigational site 4404
  • Sutton, United Kingdom
    • Kymab investigational site 4401
• United States
  • California
    • Duarte, California, United States, 91010
      • Kymab investigational site 1109
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Kymab investigational site 1102
  • Florida
    • Orlando, Florida, United States, 32806
      • Kymab investigational site 1108
    • Sarasota, Florida, United States, 34232
      • Kymab investigational site 1104
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Kymab investigational site 1103
  • Texas
    • Houston, Texas, United States, 77030
      • Kymab investigator site 1101

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥18 years (≥20 years in Taiwan)
• Histologically documented advanced/metastatic malignancies

• Phase 1 and Phase 2 participants with advanced/metastatic malignancies who have measurable disease (non-measurable disease is allowed only in Phase 1) as determined by RECIST 1.1 will be eligible if, according to the National Comprehensive Cancer Network (NCCN) guidelines, there are no available therapies known to confer a clinical benefit for their disease, or they have exhausted all such available options. Additionally, the following specific tumor indications will be enrolled:

  1. Phase 1: Participants with advanced/metastatic malignancies, and preferred indications (non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), hepatocellular carcinoma (HCC), melanoma, cervical, esophageal, gastric, renal, pancreatic, and triple negative breast cancer)
  2. Phase 2 KY1044 single agent: Participants with advanced/metastatic malignancies in indications in which signs of anti-tumor activity (Complete Response (CR), Partial Response (PR) or durable stable disease (SD) with tumor shrinkage that does not qualify for PR) were seen during the dose escalation of KY1044 as single agent

  3. Phase 2 KY1044 in combination with atezolizumab: Participants with advanced/metastatic malignancies in the selected indications below, and/or indications which have shown promising activity in Phase 1:

     • NSCLC (anti-PD-(L)1 therapy naïve and pre-treated between 1 and 2 prior lines of systemic therapy for advanced disease)
     • Gastric (anti-PD-(L)1 therapy naïve and pre-treated)
     • Recurrent and/or metastatic HNSCC (anti-PD-(L)1 therapy naïve and pre-treated between 1 and 2 prior lines of systemic therapy for advanced disease)
     • Esophageal (anti-PD-(L)1 therapy naïve and pre-treated)
     • Cervical (anti-PD-(L)1 therapy naïve and pre-treated)
     • Indications, in which signs of anti-tumor activity has been observed in Phase 1 with KY1044 in combination with atezolizumab
• Prior therapy with anti-PD-(L)1 inhibitors is allowed provided any toxicity attributed to prior anti-PD-(L)1-directed therapy did not lead to discontinuation of therapy
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
• Life expectancy longer than 12 weeks
• Must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy according to the treating institution's guidelines. Participants must be willing to undergo a new tumor biopsy at screening, and during therapy on the study

Exclusion Criteria:

• Presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that require local CNS-directed therapy, or increasing doses of corticosteroids within the prior 2 weeks of first dose of study treatment
• History of severe hypersensitivity reactions to other monoclonal antibodies and/or their excipients
• Known presence of neutralizing anti-atezolizumab antibodies (for patients previously treated with atezolizumab)
• Having out of range laboratory values: creatinine, bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), absolute neutrophil count (ANC), platelet count, hemoglobin

• Impaired cardiac function or clinically significant cardiac disease, including any of the following:

  1. Clinically significant and/or uncontrolled heart disease such as congestive heart failure requiring treatment (New York Heart Association [NYHA] Grade ≥2), uncontrolled hypertension or clinically significant arrhythmia
  2. QTcF >470 msec on screening (electrocardiogram) ECG using Fridericia's formula (QTcF) or congenital long QT syndrome
  3. Acute myocardial infarction or unstable angina pectoris
• Known human immunodeficiency virus (HIV), active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection
• Malignant disease, other than that being treated in this study
• Any medical condition that would, in the Investigator's judgment, prevent participation in the clinical study due to safety concerns, compliance with clinical study procedures or interpretation of study results
• Active autoimmune disease or a documented history of autoimmune disease
• Participants previously exposed to anti-PD-(L)1 treatment who are not adequately treated for skin rash or had no replacement therapy for endocrinopathies should be excluded
• Participants with a history of drug-induced pneumonitis or current pneumonitis
• Systemic steroid therapy or any immunosuppressive therapy. Topical, inhaled, nasal, and ophthalmic steroids are not prohibited
• Use of live attenuated vaccines against infectious diseases within 4 weeks of the first dose of study treatment. SARS-CoV-2 vaccines authorized for use by the competent local regulatory health authorities for active immunization to prevent COVID 19 are allowed (unless the vaccine is live or live attenuated) and must be given in accordance with the prevailing immunization guidelines.
• Anti-CTLA4, anti-PD-(L)1 treatment within 4 weeks of the first dose of study treatment
• Pre-treatment with anti-CTLA4 antibodies in combination with any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathway
• Presence of Common Terminology Criteria for Adverse Events version 5 (CTCAE v5) ≥Grade 2 toxicity (except alopecia, peripheral neuropathy and ototoxicity, which are excluded if CTCAE v5 ≥Grade 3) due to prior cancer therapy
• Radiotherapy within 2 weeks of the first dose of study treatment, except for palliative radiotherapy to a limited field, such as for the treatment of bone pain or a focally painful tumor mass. To allow evaluation for response to treatment, participants enrolled in the Phase 2 part must have remaining measurable disease that has not been irradiated
• Pregnant or lactating women

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: KY1044 monotherapy phase 1; KY1044 monotherapy dose escalation	Drug: KY1044; A human anti-ICOS monoclonal antibody
Experimental: KY1044 and atezolizumab phase 1; KY1044 and atezolizumab combination dose escalation	Drug: KY1044 and atezolizumab; A human anti-ICOS monoclonal antibody in combination with anti-PD-L1 monoclonal antibody (atezolizumab)
Experimental: KY1044 monotherapy phase 2; KY1044 monotherapy	Drug: KY1044; A human anti-ICOS monoclonal antibody
Experimental: KY1044 and atezolizumab phase 2; KY1044 and atezolizumab combination	Drug: KY1044 and atezolizumab; A human anti-ICOS monoclonal antibody in combination with anti-PD-L1 monoclonal antibody (atezolizumab)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) (Phase 1)	Up to 48 months
Tolerability: Number of dose interruptions, reductions and dose intensity (Phase 1)	Up to 48 months
Overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (Phase 2)	Up to 48 months
Incidence of Dose Limiting Toxicities (DLTs) with KY1044 as single agent (Phase 1)	Within first 21 days of treatment
Incidence of DLTs with KY1044 in combination with atezolizumab (Phase 1)	Within first 21 days of treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Best overall response (BOR) per RECIST 1.1	Up to 48 months
Progression Free Survival (PFS) per RECIST 1.1	Up to a PFS event, approximately every 3 months
Duration of Response (DOR) per RECIST 1.1	Up to a PFS event, approximately every 3 months
ORR per Immune-Related Response Evaluation Criteria in Solid Tumors (iRECIST) (Phase 1 and Phase 2)	Up to 48 months
PFS per iRECIST (Phase 1 and Phase 2)	Up to 48 months
ORR per RECIST 1.1 (Phase 1)	Up to 48 months
Survival rate	At 12 and 24 months
Safety: Incidence and severity of AEs and SAEs (Phase 2)	Up to 48 months
Number of dose interruptions, reductions and dose intensity (Phase 2)	Up to 48 months
Maximum Concentration (Cmax) of KY1044 and of atezolizumab if in combination	Up to 48 months
Half-life (t1/2) of of KY1044 and of atezolizumab if in combination	Up to 48 months
Number of participants with anti-KY1044 and anti-atezolizumab antibodies	Up to 48 months
Number of participants with presence of tumor-infiltrating lymphocytes (TILs) as determined by expression of ICOS (Inducible T cell Costimulator), FOXP3 (Forkhead box P3) and CD8 cells	Up to 48 months

Collaborators and Investigators

• Sponsor: Kymab Limited
• Collaborators: Sanofi
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): January 28, 2019
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): April 1, 2024

Study Registration Dates

• First Submitted: January 17, 2019
• First Submitted That Met QC Criteria: February 1, 2019
• First Posted (Actual): February 4, 2019

Study Record Updates

• Last Update Posted (Actual): November 28, 2023
• Last Update Submitted That Met QC Criteria: November 27, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Breast Diseases; Head and Neck Neoplasms; Kidney Neoplasms; Carcinoma, Squamous Cell; Breast Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carcinoma, Renal Cell; Carcinoma; Squamous Cell Carcinoma of Head and Neck; Triple Negative Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Atezolizumab
• Other Study ID Numbers: KY1044-CT01; Sanofi Study ID (Other Identifier: TCD17370)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at https://vivli.org

Drug and device information, study documents

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