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
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.
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
5. 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.
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
8. Treatment-related toxicities (except alopecia) must ≤ Grade 1 at the time of
allocation according to CTCAE version 5.0.
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
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
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
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
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
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. 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
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
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
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)
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
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.
- 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
- 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
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.