FAQs COMPOSE

At least 202 patients with advanced Grade 2 and Grade 3 GEP-NETs will be randomized at a ratio of 1:1 by a computerized system. You are equally as likely to receive RPT with n.c.a. Lutetium 177 edotreotide as you are to receive a standard therapy with CAPTEM, everolimus or FOLFOX. Neither you nor your trial doctor will be able to choose which group you will be assigned to.

• Half of patients are planned to receive RPT  with n.c.a. Lutetium 177 edotreotide with six cycles, administered as an infusion (second infusion at six weeks, then subsequent infusions at two-month intervals).

To protect the kidneys, 30-60 minutes before each cycle with RPT a specific Amino-Acid Solution (AAS) will be given as an infusion over 4-6 hours.

• Half of patients are planned to receive either CAPTEM or everolimus or FOLFOX. The appropriate standard therapy will be determined by your trial doctor based on your individual benefit-risk assessment and according to local prescribing information and guidelines.

According to your trial doctor’s assessment based on the following inclusion criteria, you may be able to participate in the COMPOSE trial:

• Your NET started in the gastrointestinal tract or pancreas (GEP-NET)
• Your GEP-NET is growing rapidly and classified as a well-differentiated or metastatic Grade 2 or Grade 3 tumor (Ki-67 index of 15 to 55, inclusive)
• Your tumor has spread to other parts of the body (metastatic) and cannot be removed completely by surgery
• You have not received previous treatment for GEP-NET, or you have received a maximum of one line prior to therapy  and your GEP-NET has progressed in the past four months

Please contact your trial doctor to learn more about the inclusion and exclusion criteria and to check if you meet all requirements.

The average trial duration for each patient (treatment and follow-up observation) will be approximately four years, but this may vary on an individual patient basis. The overall time in the trial depends on multiple factors, including the individual variability of treatment response and tumor progression.

If you are assigned to the treatment with n.c.a. Lutetium 177 edotreotide, you will have an appointment at the clinic for each of the six treatment cycles. A short hospital stay (one to three days) might be required for treatment depending on local regulations and your trial doctor.

If you are assigned to a standard therapy, the administration may be performed at or near your home if recommended by the trial doctor. However, the administration and frequency of the standard therapy assigned to you will be determined by your trial doctor based on your individual benefit-risk assessment and will follow local prescribing information and guidelines.

Your trial team will conduct tests to ensure that you are ready for the treatment.

The tests may include, but are not limited to:

• a physical examination
• blood tests and a urine tests (some of them can be collected at your local laboratory)
• a pregnancy test
• a recording of the electrical signals in your heart (ECG)
• a computerized tomography (CT scan) or a magnetic resonance imaging (MRI scan) for imaging and localization of the diseased tissue
• radioactive scans to ensure your tumor has somatostatin receptors on the cell surface (SSTR+) and to detect cancer cells with increased glucose consumption

For the trial doctors to identify the tumor grade, the trial team will ask to use a sample of your tumor taken at the time of your diagnosis. You will need to have a biopsy if a suitable sample is unavailable.

You will need to complete a quality-of-life (QoL) questionnaire before the treatment can start and at set times during the trial. The questionnaire will assess how you have been feeling and what side effects, if any, you have been experiencing.

The trial team will be monitoring your health during treatment and afterwards. The trial team will tell you about possible side effects of your treatment before you start the trial. Please consult your trial doctor should you feel sick or experience any symptoms. Your trial doctor may, depending on the severity of the side effects, give you medication to treat this side effect, prescribe a break from medication, or consider stopping the trial in consultation with you.

Medical administration of radionuclide therapies such as n.c.a. Lutetium 177 edotreotide is guided by national radiation safety regulations which differ from country to country. As you will be emitting small quantities of the radioactive substance over a seven-day period following the RPT, you will be given precautions and recommendations to follow by the trial team such as:

• good hydration is recommended – if advised by the trial doctor, drink more fluids (water) than you usually do
• urinate as often as possible and observe rigorous hygiene in order to avoid risk of contamination of others (sitting down to urinate; using toilet paper after urinating; flushing the toilet twice; washing hands thoroughly and having a towel that only you use)

If you are assigned to the treatment with n.c.a. Lutetium 177 edotreotide, you will be emitting small quantities of the radioactive substance over a seven-day period following the RPT . You will be given precautions and recommendations to follow by the trial team, such as:

• limit the time visitors spend with you to 30-40 minutes per visit for 1 week after treatment; for prolonged periods, visitors should stay more than 2 meters (6 feet) away; visitors under 15 years of age and pregnant visitors should spend less time with you.
• avoid any physical contact with children or pregnant women for 1 week
• do not sleep in the same bed as your partner for 1 week
• avoid crowded public places for 1 week

The comparator treatments CAPTEM, everolimus or FOLFOX used in this trial are some of the current standard of care treatments. If you are allocated to the standard of care group, you will receive treatment with one of these drugs based on the prior benefit-risk assessment of your trial doctor and according to local practice.

• CAPTEM is a chemotherapy that combines the two orally or intravenous administered active ingredients capecitabine and temozolomide. CAPTEM inhibits the cell division of tumor cells.
• Everolimus is an orally administered immunosuppressive cancer therapy that affects the division and growth of cancer cells by blocking the enzyme mTOR.
• FOLFOX is a chemotherapy that contains the active ingredients folinic acid, fluorouracil and oxaliplatin. FOLFOX is given by intravenous infusion and affects the DNA synthesis and tumor cell division.

You may withdraw your consent to treatment at any time; however, follow-up procedures and information will continue to be collected unless you withdraw from the trial completely. You are free to withdraw from the trial at any time. If you withdraw, your regular medical care will continue unchanged.

All treatment costs will be covered. Should travel be necessary, expenses will be covered based on travel distance and country and according to sponsorship regulations.

Should travel be necessary, travel assistance will be offered, and expenses will be covered based on travel distance and country and according to local and sponsorship regulations.

If you are interested in taking part in the COMPOSE trial, please contact your attending physician or reach out to a participating trial center nearby. You can find a full list of all participating centers at the website: clinicaltrials.gov.