Efficacy of Tislelizumab and Spartalizumab Across Multiple Cancer-types in Patients with PD1-high MRNA Expressing Tumors

NCT04802876 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: ACROPOLI (SOLTI-1904)
• Study Type: interventional
• Target: 184
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, parallel group, non-randomized, multicenter phase II study to evaluate the efficacy of spartalizumab (cohorts 1 and 2) and tislelizumab (cohort 3) in monotherapy in patients with PD1-high-expressing tumors.

Conditions

MSI-H Colorectal Cancer; Melanoma; Anal Carcinoma; Mesothelioma; Triple Negative Breast Cancer; Lung Adenocarcinoma; Cholangiocarcinoma; Cervical Carcinoma; Kidney Clear Cell Carcinoma; Stomach Adenocarcinoma; Esophageal Adenocarcinoma; Uterine Adenocarcinoma; Head and Neck Squamous Cell Carcinoma; Sarcoma; Lung Squamous Cell Carcinoma; Urothelial Carcinoma; Thyroid Carcinoma; Hepatocellular Carcinoma; Uveal Melanoma; HER2-positive Breast Cancer; Pancreatic Adenocarcinoma; Squamous Esophageal Carcinoma; Epithelial Ovarian Cancer; Uterine Carcinosarcoma; Small Cell Lung Cancer; Hormone Receptor Positive / HER2-negative Breast Cancer; Lung Adenocarcinoma EGFR-mutated/ ALK Traslocation; Colorectal Adenocarcinoma; Prostate Adenocarcinoma; Carcinoma of Unknown Primary; Other Histology

Keywords

PD1; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Overall Response rate (ORR) (Cohort 3)

  Proportion of patients with best overall response of complete response (CR) or partial response (PR), as per local investigator´s assessment and according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria.

  Until objective tumor response, on average 10 months

Secondary Outcomes (14)

• Clinical Benefit Rate (CBR) in patients with high mRNA PD1 expressing tumors (Cohort 3)

  Until objective tumor response, on average 10 months

• Progression free survival (PFS) in patients with high mRNA PD1 expressing tumors (Cohort 3)

  From date of allocation to disease progression or death from any cause,whichever came first, assessed up to approximately 36 months

• Duration of response (DoR) in patients with high mRNA PD1 expressing tumors (Cohort 3)

  From date of allocation to disease progression or death from any cause,whichever came first, assessed up to approximately 36 months

• Time to response (TtR) in patients with high mRNA PD1 expressing tumors (Cohort 3)

  Until objective tumor response, on average 10 months

• Overall survival (OS) in patients with high mRNA PD1 expressing tumors (Cohort 3)

  From date of allocation to death assessed up to approximately 36 months

Study Arms (3)

Spartalizumab (PDR001) (Cohort-1 PD1-high)

EXPERIMENTAL

400mg/intravenous every 28 days

Drug: Spartalizumab

Spartalizumab (PDR001) (Cohort-2 PD1-low)

EXPERIMENTAL

400mg/intravenous every 28 days

Drug: Spartalizumab

Tislelizumab (Cohort-3 PD1-high)

EXPERIMENTAL

300mg/intravenous every 28 days

Drug: Tislelizumab

Interventions

Spartalizumab DRUG

Spartalizumab (PDR001) 400mg will be given intravenously every 28 days

Also known as: PDR001

Spartalizumab (PDR001) (Cohort-1 PD1-high); Spartalizumab (PDR001) (Cohort-2 PD1-low)

Tislelizumab DRUG

Tislelizumab 300mg will be given intravenously every 28 days

Tislelizumab (Cohort-3 PD1-high)

Eligibility Criteria

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

You may qualify if:

• Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of PD1 mRNA high-expression (cohort 1, 3) or PD1 mRNA low-expression (cohort 2) determined on the tumor sample will be enrolled in this study. Enrollment of patients \> 75 years of age is allowed after consultation and approval of the study medical monitor.
• Life expectancy \> 3 months as per investigator opinion.
• Have measurable disease based on RECIST 1.1 or RANO criteria, as appropriate to tumor type. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Have radiologic evidence of disease progression or recurrence after the previous oncologic treatment
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 10 days prior to the date of allocation.
• Have adequate organ function. Specimens must be collected within 28 days prior to the start of study treatment.
• Patients could have received a maximum of 3 lines of prior standard of care chemotherapy in the inoperable/metastatic setting.
• Treatment-related toxicities (except alopecia) must ≤ Grade 1 at the time of allocation according to CTCAE version 5.0.

You may not qualify if:

• A Women of childbearing potential who has a positive urine pregnancy test within 72 hours prior to allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
• Has received prior therapy with an anti-PD1, anti-PDL1, or anti-PDL2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor.
• Has received prior systemic anti-cancer therapy, including investigational agents within 2 weeks. Medical Monitor could consider shorter interval for kinase inhibitors or other short half-life drugs prior to allocation.
• Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline according to CTCAE version 5.0 (except alopecia). Participants with ≤Grade 2 neuropathy may be eligible.
• Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
• Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
• Use of any live vaccines against infectious diseases within 4 weeks of initiation of study treatment.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 2 weeks prior to the first dose of study treatment.
• Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 2 weeks after the last dose of the previous investigational agent.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
• Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
• Patients with thymoma are not eligible. Patients with active CNS metastases and/or carcinomatous meningitis are not eligible. Subjects with up to three cerebral metastases are eligible, if all lesions are stable and have been definitively treated with stereotactic radiation therapy, surgery or gamma knife therapy with no evidence of disease progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
• Has severe hypersensitivity (≥Grade 3) to Spartalizumab or Tislelizumab and/or any of its excipients.

Sponsors & Collaborators

• SOLTI Breast Cancer Research Group: lead
• Novartis: collaborator

Study Sites (1)

Grupo SOLTI

Barcelona, Spain

Location

Related Publications (1)

• Prat A, Paz-Ares L, Juan M, Felip E, Garralda E, Gonzalez B, Arance A, Martin-Liberal J, Gavila J, Lopez-Gonzalez A, Cejalvo JM, Izarzugaza Y, Amillano K, Corbacho JG, Saura C, Racca F, Hierro C, Sanfeliu E, Gonzalez X, Canes J, Villacampa G, Salvador F, Pascual T, Mesia R, Cervantes A, Tabernero J. SOLTI-1904 ACROPOLI TRIAL: efficacy of spartalizumab monotherapy across tumor-types expressing high levels of PD1 mRNA. Future Oncol. 2022 Oct 6. doi: 10.2217/fon-2022-0660. Online ahead of print.

  PMID: 36200668 DERIVED

MeSH Terms

Conditions

Melanoma; Anus Neoplasms; Mesothelioma; Triple Negative Breast Neoplasms; Adenocarcinoma of Lung; Cholangiocarcinoma; Uterine Cervical Neoplasms; Carcinoma, Renal Cell; Adenocarcinoma Of Esophagus; Squamous Cell Carcinoma of Head and Neck; Sarcoma; Carcinoma, Transitional Cell; Thyroid Neoplasms; Carcinoma, Hepatocellular; Uveal Melanoma; Carcinoma, Ovarian Epithelial; Small Cell Lung Carcinoma; Neoplasms, Unknown Primary

Interventions

spartalizumab; tislelizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Anus Diseases; Rectal Diseases; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms, Mesothelial; Breast Neoplasms; Breast Diseases; Adenocarcinoma; Carcinoma; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Kidney Neoplasms; Urologic Neoplasms; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Neoplasms, Connective and Soft Tissue; Endocrine Gland Neoplasms; Endocrine System Diseases; Thyroid Diseases; Liver Neoplasms; Liver Diseases; Uveal Neoplasms; Eye Neoplasms; Eye Diseases; Uveal Diseases; Ovarian Neoplasms; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplasm Metastasis; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2021
• First Posted: March 17, 2021
• Study Start: April 12, 2021
• Primary Completion: September 30, 2025
• Study Completion (Estimated): March 31, 2027
• Last Updated: March 21, 2025

Record last verified: 2025-03

Locations

ES (1)