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Safety and Efficacy of KY1044 and Atezolizumab in Advanced Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03829501
Recruitment Status : Recruiting
First Posted : February 4, 2019
Last Update Posted : April 28, 2022
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Kymab Limited

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Squamous Cell Carcinoma of Head and Neck Non-small Cell Lung Cancer Hepatocellular Carcinoma Esophageal Cancer Gastric Cancer Melanoma Renal Cell Carcinoma Pancreatic Cancer Cervical Cancer Triple Negative Breast Cancer Advanced Cancer Metastatic Cancer Drug: KY1044 Drug: KY1044 and atezolizumab Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 412 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : January 28, 2019
Estimated Primary Completion Date : May 2023
Estimated Study Completion Date : May 2023


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)




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

Secondary Outcome Measures :
  1. Best overall response (BOR) per RECIST 1.1 [ Time Frame: Up to 48 months ]
  2. Progression Free Survival (PFS) per RECIST 1.1 [ Time Frame: Up to a PFS event, approximately every 3 months ]
  3. Duration of Response (DOR) per RECIST 1.1 [ Time Frame: Up to a PFS event, approximately every 3 months ]
  4. ORR per Immune-Related Response Evaluation Criteria in Solid Tumors (iRECIST) (Phase 1 and Phase 2) [ Time Frame: Up to 48 months ]
  5. PFS per iRECIST (Phase 1 and Phase 2) [ Time Frame: Up to 48 months ]
  6. ORR per RECIST 1.1 (Phase 1) [ Time Frame: Up to 48 months ]
  7. Survival rate [ Time Frame: At 12 and 24 months ]
  8. Safety: Incidence and severity of AEs and SAEs (Phase 2) [ Time Frame: Up to 48 months ]
  9. Number of dose interruptions, reductions and dose intensity (Phase 2) [ Time Frame: Up to 48 months ]
  10. Maximum Concentration (Cmax) of KY1044 and of atezolizumab if in combination [ Time Frame: Up to 48 months ]
  11. Half-life (t1/2) of of KY1044 and of atezolizumab if in combination [ Time Frame: Up to 48 months ]
  12. Number of participants with anti-KY1044 and anti-atezolizumab antibodies [ Time Frame: Up to 48 months ]
  13. 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 [ Time Frame: Up to 48 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03829501


Contacts
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Contact: Trial Transparency Email Recommended 1-800-633-1610 ext Option 6 contact-US@sanofi.com

Locations
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United States, Connecticut
Kymab investigational site 1102 Recruiting
New Haven, Connecticut, United States, 06510
Contact: Kymab investigator         
United States, Florida
Kymab investigational site 1104 Recruiting
Sarasota, Florida, United States, 34232
Contact: Kymab investigator         
United States, Tennessee
Kymab investigational site 1103 Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
Kymab investigator site 1101 Recruiting
Houston, Texas, United States, 77030
Contact: Kymab investigator         
Italy
Kymab investigational site 3901 Recruiting
Milano, Italy
Contact: Kymab investigator         
Kymab investigational site 3903 Recruiting
Milano, Italy
Contact: Kymab Investigator         
Kymab investigational site 3902 Recruiting
Napoli, Italy
Contact: Kymab investigator         
Taiwan
Kymab investigational site 8801 Recruiting
Taipei, Taiwan
Contact: Kymab investigator         
United Kingdom
Kymab investigational site 4405 Recruiting
London, United Kingdom
Contact: Kymab investigator         
Kymab investigational site 4402 Recruiting
Manchester, United Kingdom
Contact: Kymab investigator         
Kymab investigational site 4404 Recruiting
Oxford, United Kingdom
Contact: Kymab investigator         
Kymab investigational site 4401 Recruiting
Sutton, United Kingdom
Contact: Kymab investigator         
Sponsors and Collaborators
Kymab Limited
Sanofi
Investigators
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Study Director: Clinical Sciences & Operations Sanofi
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Responsible Party: Kymab Limited
ClinicalTrials.gov Identifier: NCT03829501    
Other Study ID Numbers: KY1044-CT01
Sanofi Study ID ( Other Identifier: TCD17370 )
First Posted: February 4, 2019    Key Record Dates
Last Update Posted: April 28, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Renal Cell
Triple Negative Breast Neoplasms
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Carcinoma, Squamous Cell
Adenocarcinoma
Urogenital Neoplasms
Kidney Neoplasms
Urologic Neoplasms
Kidney Diseases
Urologic Diseases
Head and Neck Neoplasms
Breast Neoplasms
Breast Diseases
Skin Diseases
Atezolizumab
Antineoplastic Agents