S095029 as Monotherapy and in Combination With Sym021 in Patients With Advanced Solid Tumor Malignancies Followed by an Expansion Part With Triple Combinations in Patients With Metastatic Gastric or Colorectal Cancers

A Phase 1a/1b, Open-label, Multicenter Trial Investigating the Safety, Tolerability, and Preliminary Anti-neoplastic Activity of S095029 (Anti-NKG2A) as Monotherapy and in Combination With Sym021 (Anti-PD-1) in Patients With Advanced Solid Tumor Malignancies Followed by an Expansion Part With Triplet Combinations of S095029 and Sym021 and an Anti-HER2 mAb or Anti-EGFR mAbs (Futuximab/Modotuximab) in Patients With Metastatic Gastric or Colorectal Cancers

The purpose of the study is to investigate the safety, tolerability, and preliminary anti-neoplastic activity of S095029 alone and in combination with Sym021 in patients with advanced solid tumor malignancies followed by an expansion phase of triple combinations.

Study Overview

• Status: Active, not recruiting
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: S095029; Drug: S95029 and Sym021; Drug: S095029 and Sym021 and anti-HER2 therapy; Drug: Dose expansion 2b: S095029 and Sym021 and futuximab/modotuximab

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Institut de Recherches Internationales Servier, Clinical Studies Department; Phone Number: +33 1 55 72 43 66; Email: scientificinformation@servier.com

Study Locations

• Canada
  • Toronto, Canada
    • Princess Margaret Cancer Centre
• United States
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • START Midwest
  • Texas
    • Dallas, Texas, United States, 75230
      • Mary Crowley Cancer Research
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • The START Center for Cancer Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Dose escalation part:

Inclusion Criteria:

• Histologically or cytologically confirmed unresectable, locally advanced or metastatic solid tumor malignancies
• Patients with a malignancy not amenable to surgical intervention
• Patients with measurable disease and progression radiologically assessed
• Patients with disease progression after treatment with available standard of care therapies that are known to confer clinical benefit or who are intolerant to treatment.
• Patients with available archived tumor biopsy specimens or agree to mandatory biopsy
• Estimated life expectancy ≥ 12 weeks
• Adequate haematological function
• Adequate renal function
• Adequate hepatic function

Exclusion Criteria:

• Pregnant and lactating women
• Major surgery within 4 weeks prior to the first IMP administration or not recovered from the surgery
• Patients with serious/active/uncontrolled infection or infection requiring parenteral antibiotics, within 2 weeks prior to first IMP administration
• Active Hepatitis B Virus infection
• Carriers of HIV antibodies
• Patients with active thrombosis, or a history of deep vein thrombosis or pulmonary embolism, within 4 weeks prior to first IMP administration
• History of organ transplantation
• History of gastrointestinal perforation, or intra-abdominal abscess within 28 days of inclusion
• History of cirrhosis
• History of pulmonary fibrosis or relevant uncontrolled chronic pulmonary condition
• Treatment with systemic immunosuppressive therapy
• Active autoimmune disease
• Administration of a live vaccine within 28 days prior to inclusion

Cohort expansion part 2a:

Inclusion Criteria:

• Histologically proven metastatic HER2+ gastric cancer
• Have received treatment with first line of standard therapy and eligible for second line

Exclusion Criteria:

Same criteria as for Part 1 with the addition of:

- Left ventricle ejection fraction < 50%

Cohort expansion part 2b:

Inclusion Criteria:

• Patients with confirmed adenocarcinoma of metastatic colorectal cancer
• Patients must have a wild-type gene status for KRAS (exons 2, 3, 4), NRAS (exons 2, 3, 4) and BRAF (absence of V600E mutation) in a tumor biopsy collected at time of screening.

Exclusion Criteria:

Same criteria as for dose escalation part with the addition of:

• Patients with a significant gastrointestinal abnormality
• Patients with skin rash of Grade > 1 from prior anti-EGFR

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose escalation 1a: S95029	Drug: S095029; S095029 will be administered via IV infusion every 2 weeks. Once the DLT evaluations period at the second dose level is completed and it is deemed as safe, the dose escalation part 1b will be initiated.
Experimental: Dose escalation 1b: S95029 and Sym021	Drug: S95029 and Sym021; Sym021 will be administered at a fixed dose of 200mg. S095029 will be administered via IV infusion every 2 weeks. Once the RP2D dose of S95029 in combination with Sym21 is defined, dose expansion will begin.
Experimental: Dose expansion 2a: S095029 and Sym021 and anti-HER2 therapy	Drug: S095029 and Sym021 and anti-HER2 therapy; Patients will be administered with S095029, Sym021 and anti-HER2 therapy.
Experimental: Dose expansion 2b: S095029 and Sym021 and futuximab/modotuximab	Drug: Dose expansion 2b: S095029 and Sym021 and futuximab/modotuximab; Patients will be administered with S095029, Sym021 and futuximab/modotuximab.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events (AEs) (Dose escalation part)	Incidence, severity, and relationship of AEs	Through study completion, up to 2 years
Incidence of dose limiting toxicities (DLTs) (Dose escalation part)	DLTs observed during a 28-day period	At the end of Cycle 1 (each cycle is 28 days)
Assessment of antitumor activity using RECIST v1.1 (Dose expansion part)	Objective Response Rate	Through study completion, up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (Dose escalation part)		Through study completion, up to 2 years
Clinical Benefit Rate (CBR) (Dose escalation and dose expansion parts)	Assessment based on complete response, partial response and stable disease ≥ 6 months	Through study completion, up to 2 years
Duration of response (DOR) (Dose escalation and dose expansion parts)		Through study completion, up to 2 years
Progression Free Survival (PFS) (Dose escalation and dose expansion parts)		Through study completion, up to 2 years
Overall Survival (OS) (Dose escalation and dose expansion parts)		Through study completion, up to 2 years

Collaborators and Investigators

• Sponsor: Institut de Recherches Internationales Servier
• Collaborators: ADIR, a Servier Group company
• Investigators: Principal Investigator: Nehal Lakhani MD, MD, PhD, Director of Clinical Research START Midwest

Publications and helpful links

Helpful Links

• Find Results on Servier Clinical Trial Data website

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2021
• Primary Completion (Actual): February 1, 2024
• Study Completion (Estimated): July 31, 2024

Study Registration Dates

• First Submitted: October 14, 2021
• First Submitted That Met QC Criteria: December 6, 2021
• First Posted (Actual): December 17, 2021

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Adults; Advanced solid tumors; Anti-EGFR; Futuximab/modotuximab; Sym21; Triplet combination; Anti-HER2
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplasms; Colorectal Neoplasms
• Other Study ID Numbers: CL1-95029-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data.

Access can be requested for all interventional clinical studies:

• used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
• where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope.

In addition, access can be requested for all interventional clinical studies in patients:

• sponsored by Servier
• with a first patient enrolled as of 1 January 2004 onwards
• for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.

• IPD Sharing Time Frame: After Marketing Authorisation in EEA or US if the study is used for the approval.
• IPD Sharing Access Criteria: Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Study Data/Documents

1. Individual Participant Data Set
2. Study Protocol
3. Statistical Analysis Plan
4. Informed Consent Form
5. Clinical Study Report
6. Study-level clinical trial data

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No