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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT06184035




Registration number
NCT06184035
Ethics application status
Date submitted
6/12/2023
Date registered
28/12/2023
Date last updated
28/12/2023

Titles & IDs
Public title
A Dose Escalation and Expansion Study of [177Lu]Lu-SN201 in Participants With Advanced Cancer
Scientific title
A Phase I/IIa, Dose Escalation and Dose Expansion, First-in-human, Open-label, Multicenter, Single-arm Study Evaluating the Safety, Tolerability, Dosimetry, and Early Efficacy of [177Lu]Lu-SN201 in Participants With Progressive or Treatment-refractory Locally Advanced Unresectable, Metastatic or Recurrent Solid Tumors
Secondary ID [1] 0 0
2023-505224-64
Secondary ID [2] 0 0
Tumorad-01
Universal Trial Number (UTN)
Trial acronym
Tumorad
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumor 0 0
Metastatic Cancer 0 0
Unresectable Solid Tumor 0 0
Recurrent Solid Tumor 0 0
Locally Advanced Solid Tumor 0 0
Refractory Cancer 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - [177Lu]Lu-SN201

Experimental: Phase I/IIa Dose escalation and dose expansion - Participants will initially receive 1 cycle of [177Lu]Lu-SN201 via slow intravenous infusion and progress to up to 3 cycles, provided retreatment criteria are met before the start of each cycle, occurring every 6 weeks (with an allowable window to delay each cycle by +3 weeks per retreatment criteria).
Dose escalation: The study will evaluate up to 5 dose levels of [177Lu]Lu-SN201 (A1=10 MBq/kg, A2=25 MBq/kg, A=50 MBq/kg, A4= <33% of A3, A5= <33% of A4). Additional dose levels may be explored until MTD/RP2D is identified. Up to 9 participants may be enrolled at any pre-specified dose level shown to be tolerated for confirmation of MTD and/or RP2D.
Dose expansion: Once the MTD/RP2D has been defined, an expansion phase consisting of multiple tumor types, each with up to 20 participants, will be enrolled to further characterize the safety, tolerability, and assess preliminary efficacy of [177Lu]Lu-SN201 at the RP2D and/or MTD identified in Phase I.


Treatment: Drugs: [177Lu]Lu-SN201
Intravenous infusion
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase I/IIa: Frequency and severity of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
Timepoint [1] 0 0
48 months
Primary outcome [2] 0 0
Phase I/IIa: Incidence of Dose-Limiting Toxicity (DLT) during the first cycle of treatment.
Timepoint [2] 0 0
48 months
Primary outcome [3] 0 0
Phase I: Dose escalation to identify RP2D and/or MTD dose
Timepoint [3] 0 0
24 months
Primary outcome [4] 0 0
Phase IIa: Clinical benefit in solid tumor subgroups at RP2D and/or MTD
Timepoint [4] 0 0
24 months
Secondary outcome [1] 0 0
Phase I/IIa: Measure peak plasma [177Lu]Lu-SN201 activity concentration (Cmax)
Timepoint [1] 0 0
48 months
Secondary outcome [2] 0 0
Phase I/IIa: Measure plasma half-life of the [177Lu]Lu-SN201 activity
Timepoint [2] 0 0
48 months
Secondary outcome [3] 0 0
Phase I/IIa: Measure the area under the plasma concentration versus time curve (AUC) of [177Lu]Lu-SN201 activity
Timepoint [3] 0 0
48 months
Secondary outcome [4] 0 0
Phase I/IIa: Evaluation of clinical dosimetry
Timepoint [4] 0 0
48 months
Secondary outcome [5] 0 0
Phase IIa: Evaluation of clinical benefit based on disease control rates (DCR)
Timepoint [5] 0 0
12 months

Eligibility
Key inclusion criteria
Inclusion criteria:

1. Male or female participants = 18 years of age on the day of signing informed consent.

2. Histologically or cytologically documented, recurrent, locally advanced, or metastatic
solid malignancy that has failed at least one prior systemic standard therapy, or for
which standard therapy is not appropriate, or for which no standard therapy exists.

3. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

4. Life expectancy = 3 months.

5. Adequate bone marrow, liver, and renal function, as assessed by the following
laboratory requirements, to be conducted within 28 days before the start of the study
IMP administration:

1. Hemoglobin = 9.0 g/dL (transfusions are allowed).

2. Absolute neutrophil count (ANC) = 1500/mm3.

3. Platelet count = 100,000 mm3.

4. Total bilirubin = 2.5 x upper limit of normal (ULN) (in participants with liver
metastases = 5 ULN).

5. Alanine transaminase (ALT) and aspartate transaminase (AST) = 5 x ULN.

6. On a stable dose of anti-coagulation therapy will be allowed to participate if they
have no sign of bleeding or clotting and prothrombin/international normalized ratio
and partial thromboplastin time (PT/INR and PTT, respectively) test results are
compatible with the acceptable benefit-risk ratio at the Investigator's discretion.

7. Serum creatinine = 1.5 x ULN and estimated glomerular filtration rate (eGFR) > 30
mL/min/1.73 m2 (per local values).

8. Contraceptive use by men and women should be consistent with local regulations
regarding the methods of contraception for those participating in clinical studies.

1. Male participants must agree to use a highly effective method of birth control as
defined in ICH M3(R2) starting with the first dose of study medication through
120 days after the last dose of study medication.

2. Female participants of childbearing potential* must have a negative pregnancy
test documented at Screening and Baseline and be willing to use a highly
effective method of contraception** or practice abstinence starting from ICF
signature through to 120 days after the last dose of study medication.

- A female of childbearing potential is a sexually mature female who 1) has
not undergone a hysterectomy or bilateral oophorectomy, or 2) has not been
naturally postmenopausal for at least 24 consecutive months (i.e., had had
menses at any time in the preceding 24 consecutive months).

- Effective contraception is defined as contraceptive methods with a
failure rate of < 1% to prevent pregnancy (combined [estrogen and
progestogen containing] hormonal contraception associated with
inhibition of ovulation [oral, intravaginal, transdermal],
progestogen-only hormonal contraception associated with inhibition of
ovulation [oral, injectable, implantable], intrauterine device [IUD] or
intrauterine hormone-releasing system).

9. Written informed consent to study participation.

10. Be able to understand and comply with the requirements of the study, as judged by the
Investigator.

11. Phase I: At least one lesion as per RECIST v1.1.

12. Phase IIa: At least one measurable lesion as per RECIST v1.1.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

1. Unstable systemic disease (including but not limited to active infection, hepatic,
renal, or metabolic disease).

2. Clinically significant cardiac disease including any of the following:

1. Congestive heart failure requiring treatment (New York Heart Association Grade =
2).

2. LVEF of < 50%, as determined by MUGA or ECHO.

3. Uncontrolled hypertension, defined as persistent systolic blood pressure = 150
mmHg or diastolic blood pressure = 100 mmHg despite current therapy.

4. History or presence of clinically significant ventricular arrhythmias or atrial
fibrillation.

5. Clinically significant resting bradycardia.

6. Unstable angina pectoris = 3 months before the start of study treatment.

7. Acute myocardial infarction = 3 months before the start of study treatment.

8. Mean triplicate QT interval corrected for heart rate using Fridericia's formula
(QTcF) value > 480 msec (as specified in Section 10.5).

3. Known hypersensitivity to pegylated drugs or vaccines (e.g., covid-19 vaccines).

4. Concurrent or active solid or hematologic malignancy within the last 2 years with a
distinct primary site or histology from the cancer being evaluated in this study
except for the following cancer types: cervical cancer in situ, treated basal cell
carcinoma, superficial bladder tumors (Ta and Tis).

5. Infections not responding to therapy or active clinically serious infections.

6. Known human immunodeficiency virus (HIV) infection, active hepatitis B virus (HBV), or
hepatitis C virus (HCV) infection requiring treatment. Participants with chronic HBV
or HCV infection are eligible at the Investigator's discretion provided that the
disease is stable and sufficiently controlled under treatment.

NB: Participants with CNS metastases may be included after discussion with Sponsor,
except for the sentinel participants.

7. Chemotherapy, experimental cancer therapy, biologic therapy, or immunotherapy within 2
weeks (or 5 half-lives, whatever is shortest) before the start of the study IMP
administration.

8. Palliative radiotherapy completed less than 2 weeks before the start of the study IMP
administration will be allowed as long as no more than 10% of the participant's bone
marrow was irradiated.

9. Not recovered to Grade 1 from any prior anti-cancer therapy, excluding alopecia.

10. Previous high-dose chemotherapy needing hemopoietin-stem-cell-rescue.

11. Major surgery, open biopsy, or significant trauma within 4 weeks before the start of
study treatment.

12. A psychiatric or functional disorder that prevents participants from providing
informed consent or following protocol instructions.

13. A participant that has a condition or is in a situation, in the Investigator's opinion
may put the individual at significant risk, may confound the study results, or may
interfere significantly with their participation in the study.

14. Is currently participating and receiving study therapy or has participated in a study
of an investigational agent and received study therapy or used an investigational
device within 2 weeks or 5 half-lives of the agent, whichever is the shortest.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/11/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2027
Actual
Sample size
Target
90
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment hospital [1] 0 0
Cancer Research South Adelaide - Adelaide
Recruitment hospital [2] 0 0
St Vincent Hospital Melbourne - Melbourne
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
3065 - Melbourne

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Spago Nanomedical AB
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this first-in-human (FIH) study is to determine the maximum tolerated dose
(MTD) and to characterize the safety, tolerability, PK, and dosimetry profile of
[177Lu]Lu-SN201 in adult participants with advanced solid tumors who have no standard of care
treatment options.

[177Lu]Lu-SN201 is a radiolabeled, nanomedical investigational medicinal product (IMP) whose
mechanism of delivery is based on the Enhanced Permeability and Retention (EPR) effect.
Trial website
https://clinicaltrials.gov/ct2/show/NCT06184035
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Chief Development Officer
Address 0 0
Country 0 0
Phone 0 0
+46 46 81188
Fax 0 0
Email 0 0
info@spagonanomedical.se
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT06184035