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

NCT03829501 | Terminated Phase 1 Results DMC FDA Drug

• 4 other identifiers: KY1044-CT01Sanofi Study ID2018-003172-12U1111-1269-6777
• Study Type: interventional
• Target: 222
• Locations: 6 countries
• Sites: 22

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

Outcome Measures

Primary Outcomes (6)

• Phase 1: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)

  An adverse event (AE) was any untoward medical occurrence in a participant administered a pharmaceutical product, which did not necessarily have a causal relationship with this treatment. An serious AE (SAE) was any AE that: * resulted in death; * was life-threatening; * resulted in inpatient hospitalization or prolongation of existing hospitalization; * resulted in a persistent or significant disability/incapacity; * resulted in congenital anomaly/birth defect in the offspring of a participant who received IMPs; * constituted an important medical event. Clinically significant changes in laboratory parameters, vital signs and electrocardiogram results were reported as AEs. A TEAE was defined as an AE observed after starting administration of the specific treatment.

  From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment; maximum duration of treatment exposure was up to approximately 212 weeks

• Phase 1: Number of Participants Experiencing Dose Changes

  Dose changes were defined as infusion interruption and dose reduction.

  From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment; maximum duration of treatment exposure was up to approximately 212 weeks

• Phase 1: Absolute Dose Intensity

  Absolute dose intensity was calculated as cumulative dose received (mg) / study treatment duration (weeks).

  From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment; maximum duration of treatment exposure was up to approximately 212 weeks

• Phase 1: Relative Dose Intensity

  Relative dose intensity was calculated as the cumulative dose received (mg) / initial planned cumulative dose (mg). Initial planned cumulative dose was calculated as the starting dose multiplied by the scheduled number of administrations within the study treatment duration.

  From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment; maximum duration of treatment exposure was up to approximately 212 weeks

• Phase 1: Number of Participants Experiencing Dose Limiting Toxicities (DLTs)

  A DLT was defined as a clinically relevant AE or abnormal laboratory value of Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0) ≥ Grade 3 assessed as unrelated to disease, PD, inter-current illness or concomitant medications, which occurs within the first cycle (21 days) of treatment with alomfilimab as single agent or in combination with atezolizumab during the dose escalation part of the study.

  From first dose of study treatment (Day 1) up to 21 days

• Phase 2: Overall Response Rate (ORR) Per RECIST 1.1

  ORR was the percentage of participants with a measurable disease at baseline and with a confirmed response of complete response (CR) or partial response (PR) according to RECIST v1.1 as the best response. The response is confirmed by a later scan conducted at least 4 weeks after the initial response is observed. The 95% confidence interval (CI) was calculated using the exact binomial method (Clopper-Pearson). CR: disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to \< 10 mm. All lymph nodes must have been non-pathological in size (\< 10mm short axis). PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters.

  From first dose of study treatment (Day 1) up to the end of the long term follow-up, approximately 162 weeks

Secondary Outcomes (15)

• Best Overall Response (BOR) Per RECIST 1.1

  From first dose of study treatment (Day 1) up to the end of the long term follow-up, approximately 236 and 162 weeks for Phase 1 and 2, respectively

• Progression-free Survival (PFS) Per RECIST 1.1

  From first dose of study treatment (Day 1) up to the end of the long term follow-up, approximately 236 and 162 weeks for Phase 1 and 2, respectively

• Duration of Response Per RECIST 1.1

  From first dose of study treatment (Day 1) up to the end of the long term follow-up, approximately 236 and 162 weeks for Phase 1 and 2, respectively

• ORR Per iRECIST

  From first dose of study treatment (Day 1) up to the end of the long term follow-up, approximately 236 and 162 weeks for Phase 1 and 2, respectively

• PFS Per iRECIST

  From first dose of study treatment (Day 1) up to the end of the long term follow-up, approximately 236 and 162 weeks for Phase 1 and 2, respectively

Study Arms (4)

Phase 1: Alomfilimab Monotherapy

EXPERIMENTAL

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

Drug: Alomfilimab

Phase 1: Alomfilimab + Atezolizumab Combination Therapy

EXPERIMENTAL

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

Drug: Alomfilimab; Drug: Atezolizumab

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

EXPERIMENTAL

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.

Drug: Alomfilimab; Drug: Atezolizumab

Phase 2: Alomfilimab + Atezolizumab in Pre-treated Participants

EXPERIMENTAL

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.

Drug: Alomfilimab; Drug: Atezolizumab

Interventions

Alomfilimab DRUG

A human anti-ICOS monoclonal antibody

Also known as: KY1044, SAR445256

Phase 1: Alomfilimab + Atezolizumab Combination Therapy; Phase 1: Alomfilimab Monotherapy; Phase 2: Alomfilimab + Atezolizumab in Anti-PD-(L)1 Naïve Participants; Phase 2: Alomfilimab + Atezolizumab in Pre-treated Participants

Atezolizumab DRUG

An anti-PD-L1 monoclonal antibody

Also known as: TECENTRIQ

Phase 1: Alomfilimab + Atezolizumab Combination Therapy; Phase 2: Alomfilimab + Atezolizumab in Anti-PD-(L)1 Naïve Participants; Phase 2: Alomfilimab + Atezolizumab in Pre-treated Participants

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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)
• 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
• 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

You may not qualify if:

• 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:
• 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
• QTcF \>470 msec on screening (electrocardiogram) ECG using Fridericia's formula (QTcF) or congenital long QT syndrome
• 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

Sponsors & Collaborators

• Kymab Limited: lead
• Sanofi: collaborator

Study Sites (22)

Kymab investigational site 1109

Duarte, California, 91010, United States

Location

Kymab investigational site 1102

New Haven, Connecticut, 06510, United States

Location

Kymab investigational site 1108

Orlando, Florida, 32806, United States

Location

Kymab investigational site 1104

Sarasota, Florida, 34232, United States

Location

Kymab investigational site 1103

Nashville, Tennessee, 37203, United States

Location

Kymab investigator site 1101

Houston, Texas, 77030, United States

Location

Kymab investigational site 3601

Nyíregyháza, Szabolcs-Szatmár-Bereg, 4400, Hungary

Location

Kymab investigational site 3602

Budapest, 1122, Hungary

Location

Kymab investigational site 3904

Meldola, Forlì-Cesena, 47014, Italy

Location

Kymab investigational site 3906

Candiolo, Torino, 10060, Italy

Location

Kymab investigational site 3901

Milan, Italy

Location

Kymab investigational site 3903

Milan, Italy

Location

Kymab investigational site 3902

Napoli, Italy

Location

Kymab investigational site 3910

Roma, Italy

Location

Kymab investigational site 3908

Turin, 10128, Italy

Location

Kymab investigational site 4801

Siedlce, Masovian Voivodeship, 04-141, Poland

Location

Kymab investigational site 8806

Changhua, Changhwa, 505, Taiwan

Location

Kymab investigational site 8801

Taipei, Taiwan

Location

Kymab investigational site 4405

London, United Kingdom

Location

Kymab investigational site 4402

Manchester, United Kingdom

Location

Kymab investigational site 4404

Oxford, United Kingdom

Location

Kymab investigational site 4401

Sutton, United Kingdom

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Carcinoma, Non-Small-Cell Lung; Carcinoma, Hepatocellular; Esophageal Neoplasms; Stomach Neoplasms; Melanoma; Carcinoma, Renal Cell; Pancreatic Neoplasms; Uterine Cervical Neoplasms; Triple Negative Breast Neoplasms; Neoplasm Metastasis

Interventions

atezolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Liver Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Gastrointestinal Neoplasms; Esophageal Diseases; Gastrointestinal Diseases; Stomach Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Genital Diseases; Breast Neoplasms; Breast Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2019
• First Posted: February 4, 2019
• Study Start: January 28, 2019
• Primary Completion: October 3, 2024
• Study Completion: October 3, 2024
• Last Updated: April 2, 2025
• Results First Posted: April 2, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share

Locations

GB (4); US (6); TW (2); HU (2); PL (1); IT (7)