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

Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05162755
• Other study ID #: CL1-95029-001
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: October 15, 2021
• Est. completion date: July 31, 2024

Study information

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

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 51
• Est. completion date: July 31, 2024
• Est. primary completion date: February 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Neoplasms
• Solid Tumor

Intervention

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.
• 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.
• S095029 and Sym021 and anti-HER2 therapy
Patients will be administered with S095029, Sym021 and anti-HER2 therapy.
• Dose expansion 2b: S095029 and Sym021 and futuximab/modotuximab
Patients will be administered with S095029, Sym021 and futuximab/modotuximab.

Locations

Country	Name	City	State
Canada	Princess Margaret Cancer Centre	Toronto
United States	Mary Crowley Cancer Research	Dallas	Texas
United States	START Midwest	Grand Rapids	Michigan
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	The START Center for Cancer Care	San Antonio	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Institut de Recherches Internationales Servier	ADIR, a Servier Group company

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse Events (AEs) (Dose escalation part)	Incidence, severity, and relationship of AEs	Through study completion, up to 2 years
Primary	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)
Primary	Assessment of antitumor activity using RECIST v1.1 (Dose expansion part)	Objective Response Rate	Through study completion, up to 2 years
Secondary	Objective Response Rate (Dose escalation part)		Through study completion, up to 2 years
Secondary	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
Secondary	Duration of response (DOR) (Dose escalation and dose expansion parts)		Through study completion, up to 2 years
Secondary	Progression Free Survival (PFS) (Dose escalation and dose expansion parts)		Through study completion, up to 2 years
Secondary	Overall Survival (OS) (Dose escalation and dose expansion parts)		Through study completion, up to 2 years

External Links

•   Find Results on Servier Clinical Trial Data website