Safety and Efficacy of KY1044 and Atezolizumab in Advanced Cancer

Non-small Cell Lung Cancer Clinical Trial

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 Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03829501
• Other study ID #: KY1044-CT01
• Secondary ID: Sanofi Study ID
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: January 28, 2019
• Est. completion date: August 5, 2024

Study information

• Verified date: April 2024
• Source: Kymab Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 280
• Est. completion date: August 5, 2024
• Est. primary completion date: August 5, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Cancer
• Carcinoma
• Carcinoma, Renal Cell
• Cervical Cancer
• Esophageal Cancer
• Gastric Cancer
• Hepatocellular Carcinoma
• Melanoma
• Metastatic Cancer
• Non-small Cell Lung Cancer
• Pancreatic Cancer
• Renal Cell Carcinoma
• Squamous Cell Carcinoma of Head and Neck
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Drug:
• KY1044
A human anti-ICOS monoclonal antibody
• KY1044 and atezolizumab
A human anti-ICOS monoclonal antibody in combination with anti-PD-L1 monoclonal antibody (atezolizumab)

Locations

Country	Name	City	State
Hungary	Kymab investigational site 3602	Budapest
Hungary	Kymab investigational site 3601	Nyíregyháza	Szabolcs-Szatmár-Bereg
Italy	Kymab investigational site 3906	Candiolo	Torino
Italy	Kymab investigational site 3904	Meldola	Forlì-Cesena
Italy	Kymab investigational site 3901	Milano
Italy	Kymab investigational site 3903	Milano
Italy	Kymab investigational site 3902	Napoli
Italy	Kymab investigational site 3910	Roma
Italy	Kymab investigational site 3908	Turin
Poland	Kymab investigational site 4801	Siedlce	Mazowieckie
Taiwan	Kymab investigational site 8806	Changhua City	Changhwa
Taiwan	Kymab investigational site 8801	Taipei
United Kingdom	Kymab investigational site 4405	London
United Kingdom	Kymab investigational site 4402	Manchester
United Kingdom	Kymab investigational site 4404	Oxford
United Kingdom	Kymab investigational site 4401	Sutton
United States	Kymab investigational site 1109	Duarte	California
United States	Kymab investigator site 1101	Houston	Texas
United States	Kymab investigational site 1103	Nashville	Tennessee
United States	Kymab investigational site 1102	New Haven	Connecticut
United States	Kymab investigational site 1108	Orlando	Florida
United States	Kymab investigational site 1104	Sarasota	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Kymab Limited	Sanofi

Countries where clinical trial is conducted

United States,  Hungary,  Italy,  Poland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) (Phase 1)		Up to 48 months
Primary	Tolerability: Number of dose interruptions, reductions and dose intensity (Phase 1)		Up to 48 months
Primary	Overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (Phase 2)		Up to 48 months
Primary	Incidence of Dose Limiting Toxicities (DLTs) with KY1044 as single agent (Phase 1)		Within first 21 days of treatment
Primary	Incidence of DLTs with KY1044 in combination with atezolizumab (Phase 1)		Within first 21 days of treatment
Secondary	Best overall response (BOR) per RECIST 1.1		Up to 48 months
Secondary	Progression Free Survival (PFS) per RECIST 1.1		Up to a PFS event, approximately every 3 months
Secondary	Duration of Response (DOR) per RECIST 1.1		Up to a PFS event, approximately every 3 months
Secondary	ORR per Immune-Related Response Evaluation Criteria in Solid Tumors (iRECIST) (Phase 1 and Phase 2)		Up to 48 months
Secondary	PFS per iRECIST (Phase 1 and Phase 2)		Up to 48 months
Secondary	ORR per RECIST 1.1 (Phase 1)		Up to 48 months
Secondary	Survival rate		At 12 and 24 months
Secondary	Safety: Incidence and severity of AEs and SAEs (Phase 2)		Up to 48 months
Secondary	Number of dose interruptions, reductions and dose intensity (Phase 2)		Up to 48 months
Secondary	Maximum Concentration (Cmax) of KY1044 and of atezolizumab if in combination		Up to 48 months
Secondary	Half-life (t1/2) of of KY1044 and of atezolizumab if in combination		Up to 48 months
Secondary	Number of participants with anti-KY1044 and anti-atezolizumab antibodies		Up to 48 months
Secondary	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