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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Solid Tumor

Intervention / Treatment
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* Drug: S095029
* Drug: S95029 and Sym021
* Drug: S095029 and Sym021 and anti-HER2 therapy
* Drug: Dose expansion 2b: S095029 and Sym021 and futuximab/modotuximab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose escalation 1a: S95029<br> | Drug: S095029<br>* 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.<br>|
| Experimental: Dose escalation 1b: S95029 and Sym021<br> | Drug: S95029 and Sym021<br>* 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.<br>|
| Experimental: Dose expansion 2a: S095029 and Sym021 and anti-HER2 therapy<br> | Drug: S095029 and Sym021 and anti-HER2 therapy<br>* Patients will be administered with S095029, Sym021 and anti-HER2 therapy.<br>|
| Experimental: Dose expansion 2b: S095029 and Sym021 and futuximab/modotuximab<br> | Drug: Dose expansion 2b: S095029 and Sym021 and futuximab/modotuximab<br>* Patients will be administered with S095029, Sym021 and futuximab/modotuximab.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adults, Advanced solid tumors, Sym21, Futuximab/modotuximab, Triplet combination, Anti-EGFR, Anti-HER2