Clinical Trials /

Safety and Efficacy of KY1044 and Atezolizumab in Advanced Cancer

NCT03829501

Description:

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.

Related Conditions:
  • Breast Carcinoma
  • Cervical Carcinoma
  • Esophageal Carcinoma
  • Gastric Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Hematopoietic and Lymphoid Malignancy
  • Hepatocellular Carcinoma
  • Malignant Solid Tumor
  • Melanoma
  • Non-Small Cell Lung Carcinoma
  • Pancreatic Carcinoma
  • Renal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Safety and Efficacy of KY1044 and Atezolizumab in Advanced Cancer
  • 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

Clinical Trial IDs

  • ORG STUDY ID: KY1044-CT01
  • NCT ID: NCT03829501

Conditions

  • 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

Interventions

DrugSynonymsArms
KY1044KY1044 monotherapy phase 1
KY1044 and atezolizumabKY1044 and atezolizumab phase 1

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
KY1044 monotherapy phase 1ExperimentalKY1044 monotherapy dose escalation
  • KY1044
KY1044 and atezolizumab phase 1ExperimentalKY1044 and atezolizumab combination dose escalation
  • KY1044 and atezolizumab
KY1044 monotherapy phase 2ExperimentalKY1044 monotherapy
  • KY1044
KY1044 and atezolizumab phase 2ExperimentalKY1044 and atezolizumab combination
  • KY1044 and atezolizumab

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
Time Frame:Up to 24 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:
Measure:ORR per Immune-Related Response Evaluation Criteria in Solid Tumors (iRECIST) (for phase 1 and phase 2)
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:PFS per Immune-Related Response Evaluation Criteria in Solid Tumors (iRECIST) (for phase 1 and phase 2)
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Survival rate
Time Frame:At 12 and 24 months
Safety Issue:
Description:
Measure:Best overall response (BOR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Progression Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Incidence and severity of AEs and SAEs (phase 2)
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Number of dose interruptions, reductions and dose intensity (phase 2)
Time Frame:Up to 24 months
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Kymab Limited

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