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Efficacy of Spartalizumab Across Multiple Cancer-types in Patients With PD1-high mRNA Expressing Tumors (ACROPOLI)

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ClinicalTrials.gov Identifier: NCT04802876
Recruitment Status : Recruiting
First Posted : March 17, 2021
Last Update Posted : June 10, 2021
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
SOLTI Breast Cancer Research Group

Brief Summary:
This is an open-label, single arm, non-randomized, multicenter phase II study to evaluate the efficacy of spartalizumab in monotherapy in metastatic patients with Programmed Death-1 (PD1)-high-expressing tumors.

Condition or disease Intervention/treatment Phase
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 Endometrial Carcinoma Head and Neck Squamous Cell Carcinoma Sarcoma Lung Squamous Cell Carcinoma Bladder Carcinoma Thyroid Carcinoma Hepatocellular Carcinoma Uveal Melanoma HER2-positive Breast Cancer Pancreatic Adenocarcinoma Squamous Esophageal Carcinoma Ovarian Serous Cystadenocarcinoma 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 Drug: Spartalizumab Phase 2

Detailed Description:

A molecular pre-screening will be performed to know PD1 messenger RNA (mRNA) expression levels on a tumor sample using the nCounter-based technology. This will be centrally performed at Hospital Clinic of Barcelona. If the tumor is PD1-high (Cohort 1), as defined by the pre-specified cutoff, patients (a total of 111) will receive spartalizumab 400 mg every four weeks. A cohort of 30 patients with PD1-low advanced solid tumors where the efficacy of PD1 inhibitors has been previously established (i.e. with a FDA or EMA monotherapy indication approved) will also be recruited (cohort 2).

One of the aims of the study is to show the value of the biomarker independently of the tumor histology. Thus, a wide variety of cancer-types (30 different types) will be represented.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 141 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Efficacy of Spartalizumab Across Multiple Cancer-types in Patients With PD1-high mRNA Expressing Tumors Defined by a Single and Pre-specified Cutoff
Actual Study Start Date : April 12, 2021
Estimated Primary Completion Date : December 31, 2023
Estimated Study Completion Date : December 11, 2024


Arm Intervention/treatment
Experimental: Spartalizumab (PDR001)
400mg/intravenous every 28 days
Drug: Spartalizumab
Spartalizumab (PDR001) 400mg will be given intravenously every 28 days
Other Name: PDR001




Primary Outcome Measures :
  1. Overall Response rate (ORR) [ Time Frame: Until objective tumor response, on average 10 months ]
    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.


Secondary Outcome Measures :
  1. Clinical Benefit Rate (CBR) in patients with high mRNA PD1 expressing tumors (Cohort 1) [ Time Frame: Until objective tumor response, on average 10 months ]
    Proportion of patients with a best overall response of CR, PR or an overall lesion response of Stable Disease (SD) or Non-PR/Non-progression disease (PD) lasting ≥ 24 weeks, based on local investigator´s assessment according to RECIST v1.1.

  2. Progression free survival (PFS) in patients with high mRNA PD1 expressing tumors (Cohort 1) [ Time Frame: From date of allocation to disease progression or death from any cause,whichever came first, assessed up to approximately 36 months ]
    Time from allocation to the first occurrence of disease progression, as determined locally by the investigator using RECIST v.1.1, or death from any cause, whichever occurs first.

  3. Duration of response (DoR) in patients with high mRNA PD1 expressing tumors (Cohort 1) [ Time Frame: From date of allocation to disease progression or death from any cause,whichever came first, assessed up to approximately 36 months ]
    Time from the first occurrence of a documented objective response to disease progression, as determined locally by the investigator through use of RECIST v.1.1, or death from any cause, whichever occurs first

  4. Time to response (TtR) in patients with high mRNA PD1 expressing tumors (Cohort 1) [ Time Frame: Until objective tumor response, on average 10 months ]
    Time from allocation to the first objective tumor response (tumor shrinkage of ≥30%) observed for patients who achieved a CR or PR.

  5. Overall survival (OS) in patients with high mRNA PD1 expressing tumors (Cohort 1) [ Time Frame: From date of allocation to death assessed up to approximately 36 months ]
    Time from allocation to death from any cause

  6. PFS compared to PFS on prior line of therapy (pre-PFS) in patients with high mRNA PD1 expressing tumors (Cohort 1) [ Time Frame: From date of allocation to disease progression or death from any cause,whichever came first, assessed up to approximately 36 months ]
    PFS on study treatment compared to PFS on prior line of therapy (pre-PFS).

  7. ORR in patients with low mRNA PD1-expressing tumors (Cohort 2) [ Time Frame: Until objective tumor response, on average 10 months ]
    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.

  8. CBR in patients with low mRNA PD1 expressing tumors (Cohort 2) [ Time Frame: Until objective tumor response, on average 10 months ]
    Proportion of patients with a best overall response of CR, PR or an overall lesion response of Stable Disease (SD) or Non-PR/Non-progression disease (PD) lasting ≥ 24 weeks, based on local investigator´s assessment according to RECIST v1.1.

  9. PFS in patients with low mRNA PD1 expressing tumors (Cohort 2) [ Time Frame: From date of allocation to disease progression or death from any cause,whichever came first, assessed up to approximately 36 months ]
    Time from allocation to the first occurrence of disease progression, as determined locally by the investigator using RECIST v.1.1, or death from any cause, whichever occurs first.

  10. DoR in patients with low mRNA PD1 expressing tumors (Cohort 2) [ Time Frame: From date of allocation to disease progression or death from any cause,whichever came first, assessed up to approximately 36 months ]
    Time from the first occurrence of a documented objective response to disease progression, as determined locally by the investigator through use of RECIST v.1.1, or death from any cause, whichever occurs first

  11. TtR in patients with low mRNA PD1 expressing tumors (Cohort 2) [ Time Frame: Until objective tumor response, on average 10 months ]
    Time from allocation to the first objective tumor response (tumor shrinkage of ≥30%) observed for patients who achieved a CR or PR.

  12. OS in patients with low mRNA PD1 expressing tumors (Cohort 2) [ Time Frame: From date of allocation to death assessed up to approximately 36 months ]
    Time from allocation to death from any cause

  13. PFS compared to PFS on prior line of therapy (pre-PFS) in patients with low mRNA PD1 expressing tumors (Cohort 2) [ Time Frame: From date of allocation to disease progression or death from any cause,whichever came first, assessed up to approximately 36 months ]
    PFS on study treatment compared to PFS on prior line of therapy (pre-PFS).

  14. Incidence, seriousness, treatment-related and intensity of Treatment Emergent Adverse Events [ Time Frame: During the whole treatment period (from baseline until patients' final treatment which is defined as the end of the Treatment Phase of the study, an average of 10 months ]
    Incidence, seriousness, treatment-related and intensity of Treatment Emergent Adverse Events (TEAEs) assessed by the NCI Common Terminology for Classification of Adverse Events (CTCAE) version 5, including dose reductions, delays and treatment discontinuations.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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) 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.
  2. Life expectancy > 3 months as per investigator opinion.
  3. The participant (or legally acceptable representative if applicable) provides written specific informed consent for the remaining screening tests and study procedures before inclusion in the trial.
  4. Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
  5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. Evaluation of ECOG is to be performed within 7 days prior to the date of allocation.
  6. Have adequate organ function. Specimens must be collected within 10 days prior to the start of study treatment.
  7. Patients could have received any number of previous treatments other than immune checkpoint inhibitors.
  8. Treatment-related toxicities (except alopecia) must ≤ Grade 1 at the time of allocation according to CTCAE version 5.0.

Exclusion Criteria:

  1. 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.

  2. 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.
  3. 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.

  4. 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.
  5. Use of any live vaccines against infectious diseases within 4 weeks of initiation of study treatment.
  6. 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.

  7. 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.
  8. 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.

  9. Has known active CNS metastases and/or carcinomatous meningitis. 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.
  10. Has severe hypersensitivity (≥Grade 3) to Spartalizumab and/or any of its excipients.
  11. History of severe hypersensitivity reactions to other monoclonal antibodies, which in the opinion of the investigator may pose an increased risk of serious infusion reaction.
  12. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  13. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  14. Has an active infection requiring systemic therapy.
  15. Has a known history of Human Immunodeficiency Virus (HIV).
  16. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA is detected) infection.
  17. Has a known history of active TBC (Bacillus Tuberculosis).
  18. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  19. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  20. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 150 days after the last dose of trial treatment.
  21. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 150-days after stopping treatment with spartalizumab. Highly effective contraception methods include:

    1. Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
    2. Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.
    3. Male sterilization (at least 6 months prior to screening). The vasectomized male partner should be the sole partner for that subject.
    4. Placement of a non-hormonal intrauterine device (IUD) or intrauterine system (IUS) with a documented failure rate of less than 1% per year.

    Notes:

    • Double-barrier contraception: condom and occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/cream/suppository) are not considered highly effective methods of contraception.
    • Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (i.e. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.
  22. Sexually active males, unless they use a condom during intercourse while on treatment and for 150 days after stopping treatment with spartalizumab should not father a child in this period. A condom is required to be used by vasectomized men as well during intercourse in order to prevent delivery of the drug via semen.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04802876


Contacts
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Contact: Fernando Salvador, PhD +34 616 194 478 fernando.salvador@gruposolti.org
Contact: Laura Creus laura.creus@gruposolti.org

Locations
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Spain
Ico Badalona Recruiting
Badalona, Barcelona, Spain, 08916
Contact: OLGA FERNANDEZ       ofernandez@iconcologia.net   
Principal Investigator: Mireia Margeli Vila         
Hospital Universitari Sant Joan de Reus Recruiting
Reus, Tarragona, Spain, 43204
Contact: Berta Caballe       bcaballe@grupsagessa.com   
Principal Investigator: Kepa Amillano         
IOB - H. Quironsalud Barcelona Recruiting
Barcelona, Spain, 08023
Contact: IRENE MARIMÓN       imarimon@i-crom.net   
Principal Investigator: Fabricio Racca         
Hospital Vall Hebron Recruiting
Barcelona, Spain, 08035
Contact: Cristina Saura Manich         
Principal Investigator: Cristina Saura Manich         
Hospital Clinic Barcelona Recruiting
Barcelona, Spain, 08036
Contact: Pol Sole       solei@clinic.cat   
Principal Investigator: Javier Garcia Corbacho         
Complejo Asistencial Universitario de León Recruiting
León, Spain, 24001
Contact: Pilar de la Torre       ptorref.asitec@saludcastillayleon.es   
Principal Investigator: Ana López         
Fundación Jiménez Díaz Recruiting
Madrid, Spain, 28040
Contact: Berta Martin       BMartinL@fjd.es   
Principal Investigator: Yann Izarzugaza         
Hospital Universitario 12 de Octubre Recruiting
Madrid, Spain, 28041
Contact: Raquel Rodriguez       unidadfase1.imas12@h12o.es   
Principal Investigator: Luis Paz-Ares         
Instituto Valenciano de Oncología (IVO) Recruiting
Valencia, Spain, 46009
Contact: Pedro Mallol Roselló       coordinacion@fincivo.org   
Principal Investigator: Joaquin Gavilà Gregori         
Hospital Clínico Universitario de Valencia Recruiting
Valencia, Spain, 46010
Contact: Inmaculada Blasco Blasco       iblasco@incliva.es   
Principal Investigator: Juan Miguel Cejalvo Andújar         
Sponsors and Collaborators
SOLTI Breast Cancer Research Group
Novartis
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Responsible Party: SOLTI Breast Cancer Research Group
ClinicalTrials.gov Identifier: NCT04802876    
Other Study ID Numbers: ACROPOLI (SOLTI-1904)
First Posted: March 17, 2021    Key Record Dates
Last Update Posted: June 10, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by SOLTI Breast Cancer Research Group:
PD1
Immunotherapy
Additional relevant MeSH terms:
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Breast Neoplasms
Triple Negative Breast Neoplasms
Endometrial Neoplasms
Thyroid Neoplasms
Esophageal Neoplasms
Urinary Bladder Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neoplasms, Squamous Cell
Neoplasms, Connective and Soft Tissue
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms, Mesothelial
Head and Neck Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine Gland Neoplasms
Neoplasms, Cystic, Mucinous, and Serous
Neoplasms, Complex and Mixed