Shionogi, 2023P2411(aCCeleR8-001), Ph1b/2,Open,Advanced Solid Tumors,S-531011 +/- Pembrolizumab

What is the Purpose of this Study?

Primary: -To evaluate the safety and tolerability of S-531011 and to determine the MTD and/or RP2D of S-531011. Secondary: - To evaluate the preliminary antitumor activity of S-531011 per RECIST version 1.1a. - To characterize the PK profile of S-531011. -To evaluate the host immune response (immunogenicity) to S-531011. -To evaluate serum tumor-specific markers. Exploratory: -To explore the potential pharmacodynamic markers and proof of mechanism of S-531011 in tumor tissues. -To explore the potential pharmacodynamic markers of S-531011 in PBMCs and plasma. -To explore the potential biomarkers associated with S-531011 clinical activity.

Eligibility

1. Male or female participant must be at least 18 years of age inclusive (or complies with country-specific regulatory requirements), at the time of signing the informed consent.
2. Participants with histologically or cytologically confirmed advanced (locoregionally recurrent, not amenable to curative therapy) or metastatic solid tumors who have no standard therapies with a proven clinical benefit, or who are intolerant to or unwilling to receive these therapies for any reasons.
3. Measurable disease by RECIST 1.1.
4. (Part A only) Participants should have 1 of the following tumor types: malignant melanoma (MEL), head and neck squamous cell carcinoma (HNSCC), renal cell carcinoma (RCC), urothelial carcinoma (UC), non-small cell lung cancer (NSCLC), or triple-negative breast cancer (TNBC), esophageal cancer (EC; esophageal squamous cell carcinoma and adenocarcinoma), or gastric cancer (GC; gastric and gastroesophageal junction adenocarcinoma).

Inclusion Criteria:

1. Male or female participant must be at least 18 years of age inclusive (or complies with country-specific regulatory requirements), at the time of signing the informed consent.
2. Participants with histologically or cytologically confirmed advanced (locoregionally recurrent, not amenable to curative therapy) or metastatic solid tumors who have no standard therapies with a proven clinical benefit, or who are intolerant to or unwilling to receive these therapies for any reasons.
3. Measurable disease by RECIST 1.1.
4. (Part A only) Participants should have 1 of the following tumor types: malignant melanoma (MEL), head and neck squamous cell carcinoma (HNSCC), renal cell carcinoma (RCC), urothelial carcinoma (UC), non-small cell lung cancer (NSCLC), or triple-negative breast cancer (TNBC), esophageal cancer (EC; esophageal squamous cell carcinoma and adenocarcinoma), or gastric cancer (GC; gastric and gastroesophageal junction adenocarcinoma).
5. (Part B only) Participants should have 1 of specific histologically or cytologically confirmed tumor types selected by the sponsor after the determination of tentative RP2D(s) in Part A-1.
6. (Part C only) Participants should have 1 of specific histologically or cytologically confirmed tumor types selected by the sponsor after the determination of tentative RP2D(s) in Part A-2.
7. Participants should be willing and able to provide permission to access archival formalin-fixed paraffin-embedded (FFPE) tumor tissues (as block or unstained slides) for this study.
8. Participants should be willing and able to provide both pre-treatment and on-treatment paired tumor biopsy samples.
9. (At selected sites only) Participants should be willing and able to provide both pre-treatment and on-treatment paired tumor biopsy samples. Fresh tissue samples are required as these will be used for the proof of mechanism analysis.
10. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
11. An estimated life expectancy of at least 12 weeks.
12. Adequate hematologic and organ function as confirmed by laboratory values.
13. QT interval corrected with the Fridericia formula (QTcF) ≤ 480 milliseconds in 12-lead electrocardiogram (ECG) at Screening.

Exclusion Criteria:

1. Presence or history of autoimmune diseases or immune-mediated diseases that require chronic use of systemic corticosteroids (\> 10 mg of prednisone equivalent per day), immunosuppressive agents, or disease-modifying agents.
2. Presence or history of interstitial lung disease and (non-infectious) pneumonitis that required corticosteroids.
3. Active clinically significant bacterial, viral or fungal infection, or any major episode of infection requiring hospitalization or treatment with parenteral anti-infectives within 4 weeks before the first dose of study intervention.
4. Uncontrolled or clinically significant cardiovascular disease defined as New York Heart Association (NYHA) classification III or IV.
5. A positive test for hepatitis B surface antigen (HBsAg) and/or hepatitis C virus (HCV) antibody (a confirmatory HCV RNA test if HCV antibody was positive).
6. A positive serological test for human immunodeficiency virus (HIV) infection.
7. Known history of any other relevant congenital or acquired immunodeficiency.
8. Known history of an allogeneic tissue and/or solid organ transplant.
9. Known history of severe allergy, hypersensitivity, anaphylaxis, or any serious adverse reaction to any component of study intervention or formulation components and/or any other monoclonal antibodies.
10. Women who are pregnant or breastfeeding or trying to become pregnant.
11. Clinical evidence of uncontrolled brain metastasis.
12. Known additional malignancy that is progressing or has required active treatment within the past 3 years.
13. (Parts A-2 and C only): Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137), and was discontinued from that treatment due to ≥ Grade 3 immune-related adverse event (irAE).
14. Prior treatment with systemic anticancer drugs (including any investigational medicinal products) within 28 days or 5 half-lives (whichever is shorter) before the first dose of study intervention.
15. Prior major surgery within 28 days before the first dose of study intervention.
16. Prior extended field radiotherapy within 28 days before the first dose of study intervention (within 14 days for limited field radiation for palliation) or history of radiation pneumonitis.
17. Participants who have not recovered from any previous treatment toxicities to ≤ Grade 1 or baseline (except alopecia and peripheral neuropathy) before the first dose of study intervention.
18. Prior treatment with anti-CCR8 antibody for any indication.
19. Receipt of hematopoietic growth factors (eg, granulocyte-colony stimulating factor \[G-CSF\] or erythropoietin) within 14 days before the first dose of study intervention or blood transfusions within 14 days before the first dose of study intervention.
20. Receipt of a live, attenuated vaccine within 30 days before the first dose of study intervention.

Show less

Where can I participate?

CS Cancer at The Angeles Clinic and Research Institute : Saba Mukarram

More about this Clinical Trial

What is the full name of this clinical trial?

A phase 1b/2, multicenter, open-label study of S-531011 as monotherapy and in combination with an immune checkpoint inhibitor in participants with locally advanced or metastatic solid tumors

Study Details

Disease Type/Condition

Breast, Colon, Esophagus, Kidney, Lung, Melanoma, Ovary

Principal Investigator

Hamid, Omid

Co-Investigators

Ani Balmanoukian, Cathie T Chung, Inderjit Mehmi, Iryna Singh, Justin Moyers, Kristopher Wentzel, Navid Hafez, Vi K. Chiu

Age Group

Adult

Phase

I/II

IRB Number

STUDY00001962

ClinicalTrials.gov ID

NCT05101070

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

Name

Saba Mukarram

Phone

+1 310-231-2181

MukarramS@cshs.org