Efficacy of antibodies targeting PD1 protein in patients with advanced or metastatic tumors that express high levels of PD1 biomarker.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Solti Group

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

30 Apr 2021 → 31 Jul 2025

Decision date (initial)

2024-10-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2023-508549-41-00

EudraCT number

2020-003022-22

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To assess the efficacy of tislelizumab across multiple cancer-types in patients with high mRNA PD1 expressing tumors defined by a single and pre-specified cut-off (Cohort 3)

Secondary objectives 3

1. To determine the clinical benefit of tislelizumab in patients with high mRNA PD1 expressing tumors (Cohort 3)
2. To determine the clinical benefit of spartalizumab in patients with high and low mRNA PD1-expressing tumors (Cohort 1 and 2, respectively)
3. To assess the safety and tolerability of spartalizumab and tislelizumab.

Conditions and MedDRA coding

Metastatic disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

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 (cohorts 1 and 3) or PD1 mRNA lowexpression (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 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. Note: Patient with primary central nervous system should meet the following criterion: a. Have ≥ 1 site of bi-dimensionally measurable disease (confirmed by magnetic resonance imaging [MRI] and evaluable by RANO criteria), with the size of at least one of the measurable lesions ≥ 1 cm in each dimension and noted on more than one imaging slice
5. Have radiologic evidence of disease progression or recurrence after the previous oncologic treatment.
6. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. Evaluation of ECOG is to be performed within 10 days prior to the date of allocation.
7. Have adequate organ function as per protocol defined. Specimens must be collected within 28 days prior to the start of study treatment.
8. Patients could have received a maximum of 3 lines of prior standard of care chemotherapy in the inoperable/metastatic setting. Note: A chemotherapy line in advanced disease is an anticancer regimen(s) that contains at least 1 cytotoxic chemotherapy agent and given for 28 days or longer. If a cytotoxic chemotherapy regimen was discontinued for a reason other than disease progression and lasted less than 28 days, then this regimen does not count as a "prior line of chemotherapy". Targeted agents (such as CDK 4/6 inhibitos, mTOR inhibitor, PARP inhibitors) endocrine therapies, on their own no contribute to the count of a prior line of the chemotherapy; however, regimens with such agents in combination with cytotoxic chemotherapy should be classified as one line of chemotherapy
9. Treatment-related toxicities (except alopecia) must ≤ Grade 1 at the time of allocation according to CTCAE version 5.0.

Exclusion criteria 23

1. A Women of childbearing potential who has a positive urine pregnancy test within 72 hours prior to allocation.
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 (e.g., CTLA-4, OX 40, CD137).
3. Has received prior systemic anti-cancer therapy, including investigational agents within 2 weeks.
4. Has received prior radiotherapy within 2 weeks of start of study treatment.
5. Use of any live vaccines against infectious diseases within 4 weeks of initiation of study treatment. Note: It is not recommended the use of live or attenuated COVID-19 vaccines within 4 weeks of initiation or during study treatment. However, if vaccination with these vaccines is required, please ask for advice on how to proceed the Medical Monitor
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.
7. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
8. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
9. Patients with thymoma are not eligible. Patients with active CNS metastases and/or carcinomatous meningitis are not eligible.
10. Has severe hypersensitivity (≥Grade 3) to Spartalizumab/ tislelizumab 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). For more information, see appendix 2.
13. Prior allogeneic stem cell transplantation or organ transplantation
14. Has a history of interstitial lung disease, (non-infectious) pneumonitis that required steroids or has current pneumonitis, uncontrolled lung including pulmonary fibrosis, acute lung diseases, etc. Patients with significantly impaired pulmonary function, or who require supplemental oxygen at baseline must undergo an assessment of pulmonary function at screening
15. Has an active infection requiring systemic therapy.
16. Has a known history of Human Immunodeficiency Virus (HIV).
17. 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.
18. Has a known history of active TBC (Bacillus Tuberculosis).
19. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study.
20. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
21. 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.
22. 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 /tislelizumab
23. Sexually active males, unless they use a condom during intercourse while on treatment and for 150 days after stopping treatment with spartalizumab/tislelizumab 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall Response rate (ORR) defined as the 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 endpoints 14

1. Clinical Benefit Rate (CBR) defined as the 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) defined as the 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) defined as the 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) defined as the 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) defined as the time from allocation to death from any cause (OS will be determined at the end of the study). 1.6. PFS on study treatment compared to PFS on prior line of therapy (pre-PFS).
6. ORR as per local investigator´s assessment and according to RECIST v1.1.
7. CBR based on local investigator´s assessment according to RECIST v1.1.
8. PFS as determined locally by the investigator using RECIST v.1.1, or death from any cause, whichever occurs first.
9. DoR as determined locally by the investigator through use of RECIST v.1.1, or death from any cause, whichever occurs first
10. TtR observed for patients who achieved a CR or PR.
11. OS defined as the time from allocation to death from any cause.
12. PFS on study treatment compared to PFS on prior line of therapy (pre-PFS).
13. Incidence, seriousness, treatment-related and severity (grade) of Treatment Emergent Adverse Events (TEAEs) assessed by the NCI Common Terminology for Classification of Adverse Events (CTCAE) version 5, including delays and treatment discontinuations.
14. Frequency of clinically significant abnormalities in physical examination, safety laboratory tests, urinalysis and vital signs.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Solti Group

Sponsor organisation

Solti Group

Address

Calle Balmes 89 Planta 1 Puerta 2

City

Barcelona

Postcode

08008

Country

Spain

Scientific contact point

Organisation

Solti Group

Contact name

SOLTI-Start-Up Group

Public contact point

Organisation

Solti Group

Contact name

SOLTI-Start-Up Group

Third parties 2

Locations

1 EU/EEA country · 13 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications