A Phase 1/2, Open-label, Multi-center Study of the Safety and Efficacy of Alomfilimab (KY1044) as Single Agent and in Combination With Anti-PD-L1 (Atezolizumab) in Adult Patients With Selected Advanced Malignancies

NCT ID: NCT03829501

Last Updated: 2025-04-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 222 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-28
• Study Completion Date: 2024-10-03

Brief Summary

A Phase 1/2, open label, multi-center study to evaluate the safety, efficacy and tolerability of alomfilimab 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.

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; Metastatic Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1: Alomfilimab Monotherapy

Participants will receive alomfilimab 0.8 to 240 mg as a single agent via intravenous (IV) infusion every 3 weeks (Q3W).

Group Type: EXPERIMENTAL

Alomfilimab

Intervention Type: DRUG

A human anti-ICOS monoclonal antibody

Phase 1: Alomfilimab + Atezolizumab Combination Therapy

Participants will receive alomfilimab 2.4 to 80 mg in combination with atezolizumab 1200 mg via IV infusion Q3W.

Group Type: EXPERIMENTAL

Alomfilimab

Intervention Type: DRUG

A human anti-ICOS monoclonal antibody

Atezolizumab

Intervention Type: DRUG

An anti-PD-L1 monoclonal antibody

Phase 2: Alomfilimab + Atezolizumab in Anti-PD-(L)1 Naïve Participants

Anti-PD-(L)1 naïve participants with pancreatic cancer, triple negative breast cancer (BC) or head and neck squamous cell carcinoma (HNSCC) will receive alomfilimab 2.4 to 24 mg in combination with atezolizumab 1200 mg via IV infusion Q3W.

Group Type: EXPERIMENTAL

Alomfilimab

Intervention Type: DRUG

A human anti-ICOS monoclonal antibody

Atezolizumab

Intervention Type: DRUG

An anti-PD-L1 monoclonal antibody

Phase 2: Alomfilimab + Atezolizumab in Pre-treated Participants

Pre-treated participants with pancreatic cancer, triple negative BC or HNSCC will receive alomfilimab 2.4 to 24 mg in combination with atezolizumab 1200 mg via IV infusion Q3W.

Group Type: EXPERIMENTAL

Alomfilimab

Intervention Type: DRUG

A human anti-ICOS monoclonal antibody

Atezolizumab

Intervention Type: DRUG

An anti-PD-L1 monoclonal antibody

Interventions

Alomfilimab

A human anti-ICOS monoclonal antibody

Intervention Type: DRUG

Atezolizumab

An anti-PD-L1 monoclonal antibody

Intervention Type: DRUG

Other Intervention Names

KY1044; SAR445256; TECENTRIQ

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 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 Alomfilimab 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 Alomfilimab as single agent

3. Phase 2 Alomfilimab 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 Alomfilimab 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: collaborator

Kymab Limited

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Kymab investigational site 1109

Duarte, California, 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, United States

Kymab investigational site 1103

Nashville, Tennessee, United States

Kymab investigator site 1101

Houston, Texas, United States

Kymab investigational site 3601

Nyíregyháza, Szabolcs-Szatmár-Bereg, Hungary

Kymab investigational site 3602

Budapest, , Hungary

Kymab investigational site 3904

Meldola, Forlì-Cesena, Italy

Kymab investigational site 3906

Candiolo, Torino, Italy

Kymab investigational site 3901

Milan, , Italy

Kymab investigational site 3903

Milan, , Italy

Kymab investigational site 3902

Napoli, , Italy

Kymab investigational site 3910

Roma, , Italy

Kymab investigational site 3908

Turin, , Italy

Kymab investigational site 4801

Siedlce, Masovian Voivodeship, Poland

Kymab investigational site 8806

Changhua, Changhwa, Taiwan

Kymab investigational site 8801

Taipei, , Taiwan

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 Kingdom

Countries

United States; Hungary; Italy; Poland; Taiwan; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

Sanofi Study ID

Identifier Type: OTHER

Identifier Source: secondary_id

2018-003172-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1269-6777

Identifier Type: OTHER

Identifier Source: secondary_id

KY1044-CT01

Identifier Type: -

Identifier Source: org_study_id