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Safety and Efficacy of KY1044 and Atezolizumab in Advanced Cancer

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ClinicalTrials.gov Identifier: NCT03829501
Recruitment Status : Recruiting
First Posted : February 4, 2019
Last Update Posted : August 14, 2019
Sponsor:
Information provided by (Responsible Party):
Kymab Limited

Tracking Information
First Submitted Date  ICMJE January 17, 2019
First Posted Date  ICMJE February 4, 2019
Last Update Posted Date August 14, 2019
Actual Study Start Date  ICMJE January 28, 2019
Estimated Primary Completion Date May 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 1, 2019)
  • Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Up to 24 months ]
  • Number of dose interruptions, reductions and dose intensity [ Time Frame: Up to 24 months ]
  • Overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (phase 2) [ Time Frame: Up to 24 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03829501 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 1, 2019)
  • ORR per RECIST 1.1 (phase 1) [ Time Frame: Every 8 weeks after the start of treatment for the first 16 weeks, after that every 12 weeks till the end of 24 months of treatment or until objective disease progression ]
  • ORR per Immune-Related Response Evaluation Criteria in Solid Tumors (iRECIST) (for phase 1 and phase 2) [ Time Frame: Up to 24 months ]
  • PFS per Immune-Related Response Evaluation Criteria in Solid Tumors (iRECIST) (for phase 1 and phase 2) [ Time Frame: Up to 24 months ]
  • Survival rate [ Time Frame: At 12 and 24 months ]
  • Best overall response (BOR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) [ Time Frame: Up to 24 months ]
  • Progression Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) [ Time Frame: Up to 24 months ]
  • Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) [ Time Frame: Up to 24 months ]
  • Incidence and severity of AEs and SAEs (phase 2) [ Time Frame: Up to 24 months ]
  • Number of dose interruptions, reductions and dose intensity (phase 2) [ Time Frame: Up to 24 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of KY1044 and Atezolizumab in Advanced Cancer
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • Drug: KY1044
    A human anti-ICOS monoclonal antibody
  • Drug: KY1044 and atezolizumab
    A human anti-ICOS monoclonal antibody in combination with anti-PD-L1 monoclonal antibody (atezolizumab)
Study Arms  ICMJE
  • Experimental: KY1044 monotherapy phase 1
    KY1044 monotherapy dose escalation
    Intervention: Drug: KY1044
  • Experimental: KY1044 and atezolizumab phase 1
    KY1044 and atezolizumab combination dose escalation
    Intervention: Drug: KY1044 and atezolizumab
  • Experimental: KY1044 monotherapy phase 2
    KY1044 monotherapy
    Intervention: Drug: KY1044
  • Experimental: KY1044 and atezolizumab phase 2
    KY1044 and atezolizumab combination
    Intervention: Drug: KY1044 and atezolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 1, 2019)
412
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2023
Estimated Primary Completion Date May 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 Response Evaluation Criteria in Solid Tumors version 1.1 (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)
      • Gastric (anti-PD-(L)1 therapy naïve and pre-treated)
      • HNSCC (anti-PD-(L)1 therapy naïve and pre-treated)
      • 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
  • 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 life attenuated vaccines against infectious diseases within 4 weeks of the first dose of study treatment
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Kymab Ltd +44 (0)1223 833301 clinicaltrial@kymab.com
Listed Location Countries  ICMJE Italy,   Taiwan,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03829501
Other Study ID Numbers  ICMJE KY1044-CT01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Kymab Limited
Study Sponsor  ICMJE Kymab Limited
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Kymab Ltd Kymab Ltd
PRS Account Kymab Limited
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP