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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 : February 19, 2019
Sponsor:
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 Drug: KY1044 Drug: KY1044 and atezolizumab Phase 1 Phase 2

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. Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Up to 24 months ]
  2. Number of dose interruptions, reductions and dose intensity [ Time Frame: Up to 24 months ]
  3. Overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (phase 2) [ Time Frame: Up to 24 months ]

Secondary Outcome Measures :
  1. 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 ]
  2. ORR per Immune-Related Response Evaluation Criteria in Solid Tumors (iRECIST) (for phase 1 and phase 2) [ Time Frame: Up to 24 months ]
  3. PFS per Immune-Related Response Evaluation Criteria in Solid Tumors (iRECIST) (for phase 1 and phase 2) [ Time Frame: Up to 24 months ]
  4. Survival rate [ Time Frame: At 12 and 24 months ]
  5. Best overall response (BOR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) [ Time Frame: Up to 24 months ]
  6. Progression Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) [ Time Frame: Up to 24 months ]
  7. Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) [ Time Frame: Up to 24 months ]
  8. Incidence and severity of AEs and SAEs (phase 2) [ Time Frame: Up to 24 months ]
  9. Number of dose interruptions, reductions and dose intensity (phase 2) [ Time Frame: Up to 24 months ]


Information from the National Library of Medicine

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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 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

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
Contact: Kymab Ltd +44 (0)1223 833301 clinicaltrial@kymab.com

Locations
United States, Connecticut
Kymab investigational site 1102 Not yet 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, New York
Kymab investigational site Not yet recruiting
New York, New York, United States, 10065
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 Not yet recruiting
Milan, Italy
Contact: Kymab investigator         
Kymab investigational site 3902 Not yet recruiting
Napoli, Italy
Contact: Kymab investigator         
Taiwan
Kymab investigational site 8802 Not yet recruiting
Tainan, Taiwan
Contact: Kymab investigator         
Kymab investigational site 8801 Not yet recruiting
Taipei, Taiwan
Contact: Kymab investigator         
United Kingdom
Kymab investigational site 4402 Not yet recruiting
Manchester, United Kingdom
Contact: Kymab investigator         
Kymab investigational site 4401 Not yet recruiting
Sutton, United Kingdom
Contact: Kymab investigator         
Sponsors and Collaborators
Kymab Limited
Investigators
Study Director: Kymab Ltd Kymab Ltd

Responsible Party: Kymab Limited
ClinicalTrials.gov Identifier: NCT03829501     History of Changes
Other Study ID Numbers: KY1044-CT01
First Posted: February 4, 2019    Key Record Dates
Last Update Posted: February 19, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Pancreatic Neoplasms
Stomach Neoplasms
Uterine Cervical Neoplasms
Esophageal Neoplasms
Neoplasms
Triple Negative Breast Neoplasms
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Neoplasms, Squamous Cell
Digestive System Neoplasms
Endocrine Gland Neoplasms
Liver Neoplasms
Gastrointestinal Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Kidney Neoplasms
Urologic Neoplasms
Breast Neoplasms
Carcinoma
Carcinoma, Squamous Cell
Carcinoma, Hepatocellular