Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication AFINITOR is a kinase inhibitor indicated for the treatment of: Postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer in combination with exemestane after failure of treatment with letrozole or anastrozole. FDA label
Also known as pasireotide, Pasireotide LAR, Octreotide LAR, Pasireotide (SOM230), Pasireotide s.c., Afinitor
SOM230 · 25 trials · 23 indications
PFS is defined as the time from randomization to the first occurrence of progression (centrally assessed by Blinded Independent Review Committee (BIRC) according to RECIST v1.1) or death due to any cause.
Percentage of participants who achieved biochemical control defined as GH \<1μg/L and IGF-1 \<ULN at week 36.
Percentage of participants who achieved biochemical control defined as GH \<1μg/L and IGF-1 \<ULN at week 36, for participants who had been up-titrated with pasireotide LAR 60 mg.
Percentage of participants who achieved biochemical control defined as GH \<1μg/L and IGF-1 \<ULN at week 36.
Percentage of participants who achieved biochemical control defined as GH \<1μg/L and IGF-1 \<ULN at week 36, overall by baseline diabetic status.
Percentage of participants who achieved biochemical control defined as GH \<1μg/L and IGF-1 \<ULN at week 36, by previous treatment and overall - last observation carried forward (LOCF)
Percentage of participants that attained a mean urinary free cortisol (mUFC) \<= 1.0 x upper limit of normal (ULN) at Month 7 regardless of dose up-titration at Month 4. Patients who discontinued before month 4 evaluations classed as non-responders. For patients missing month 7 mUFC assessments, the last available mUFC assessment at or after month 4 was carried forward as the month 7 mUFC assessment value.
The primary objective of this study was to compare the percentage of patients achieving biochemical control (defined as mean GH levels \<2.5 µg/L and normalization of sex- and age- adjusted IGF-1) at 24 weeks with pasireotide LAR 40 mg and pasireotide LAR 60 mg separately versus continued treatment with octreotide LAR 30 mg or lanreotide autogel (ATG) 120 mg. The primary efficacy variable is the proportion of patients with a reduction of mean GH levels to \< 2.5 µg/L and normalization of sex- and age-adjusted IGF-1 at 24 weeks.
Percentage of patients who received clinical benefit in symptom (diarrhea and/or flushing) improvement as: Diarrhea (D)+Flushing (F): Patients with a daily mean number (#) of at least four bowel movements and a total of five or more flushing episodes. Clinical Benefit Response Criteria (CBRC): \<4 daily mean bowel movements AND at least 20% reduction from Baseline in the daily mean # of bowel movements AND any reduction in the total # of flushing episodes compared with Baseline. (D) Patients with a daily mean # of at least four bowel movements and a total # of \<5 flushing episodes. (CBRC) \<4 daily mean bowel movements AND at least a 20% reduction from Baseline in the daily mean # of bowel movements. (F) Patients with a total # of at least 14 flushing episodes and a daily mean # of \<4 bowel movements (CBRC) At least a 30% reduction from Baseline in the total # of flushing episodes.
Percentage of participants with a reduction of mean GH levels to \<2.5μg/L (based on a 5-point 2-hour profile) and normalization of sex- and age-adjusted IGF-1. Post surgery = patients with prior surgery but no previous medical treatment for acromegaly De novo = patients with de novo disease who refused pituitary surgery or for whom pituitary surgery was contraindicated.
A responder in the primary efficacy analysis was a patient with a mUFC≤ULN at Month 6 and whose dose was not increased prior to Month 6.
Patients with Complete Response (CR), Partial Response (PR), or Stable Disease (SD) at Month 9 were to be considered as "progression-free" based on RECIST v1.1. Patients with missing tumor assessment, or with overall lesion response "unknown" at Month 9 were considered as "non progression-free", unless any of the following assessments at Week 48 or Week 52 indicate CR, PR, or SD, in which case the patient was to be considered as progression-free at Month 9. Patients discontinuing the study for any reason prior to the 9 month assessment were to be considered as "non progression-free".
Response rate is defined as percentage of patients with no glucose values \< 60 mg/dL at 90,120, 150 and 180 min during the Oral Glucose Tolerance Test (OGTT) at the end of s.c. dose escalation phase
Tumor volume was evaluated by MRI. MRIs were performed and processed according to the guidelines of the central evaluator's facility.The pituitary adenomas were measured by a neuro-radiologist, using manual tracing together with the imaging analysis software. The largest diameter at any plan determined the maximum diameter of the tumor. A change ≥ 20% in the original volume of the tumor was considered to be clinically significant. Evaluable participants required tumor volume assessment at baseline and at week 24.
Percentage of participants with a reduction of mean growth hormone (GH) levels to \< 2.5 µg/L and the normalization of insulin-like growth factor-1 (IGF-1) to within normal limits (age and sex related) at 3 months across all doses
Treatment Success was defined as: less than 2 episodes of vomiting on average per day for the 4 days prior to Day 14 \[from Day 10 to Day 13\] and no use of an Nasogastric Tube (NGT) since at least Day 10 and no use of an anticholinergic agent until Day 14. Treatment Failure is defined as: 2 or more episodes of vomiting per day on average for the 4 days prior to Day 14 or use of an NGT after Day 9 or use of an anticholinergic agent before Day 14 or withdrawal from the trial between Day 1 and Day 14 (included), whatever the cause.
A participant was a responder to a dose level if the mean GH level after dosing (t30, t60, t90, and t120) was below/equal to 2.5 microgram/litre (μg/L), and if the mean of IGF-1 of the two pre-dose values (t-30, t-1) was within normal limits for age-sex matched controls. If three or more of t30, t60, t90, or t120 were missing, mean GH was considered missing. If either t-30 or t-1 was missing, mean IGF-1 was considered missing. Pasireotide incident dose classes were defined by total daily doses ranges (\<1200 μg/d, 1200 to \<1500 μg/d, ≥ 1500 μg/d).
A participant was considered a responder if the mean UFC from the two 24-hour urine samples collected at Month 6 was within normal limits. The normal range for UFC is 55 to 276 nmol/day.
24-hour urine samples were collected to obtain mean UFC measurements. A negative mean change from baseline indicates improvement.
Complete Symptom Control: an average of ≤ 3 bowel movements per day for at least 15 consecutive days, with no more than 3 episodes on any given day, and no episodes of flushing over the time interval being studied. Partial Symptom Control: an average of \< 4 bowel movements per day for at least 15 consecutive days, with no more than 6 episodes per given day, and an average of fewer than 2 daily flushing episodes over the same given time interval. Treatment failure: Failure to obtain partial or complete treatment success over a consecutive 15-day period at a constant dose level.
The primary outcome is the number of hypoglycemic events occurring.
DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications as defined per study prototol. These will be evaluated according to the CTCAE v4.03.
Progression is defined as a PSA-increase of at least 25% and an absolute increase of at least 2 ng/ml from a nadir value, confirmed by a second value four weeks later.
Description: Cmax, AUCinf, AUClast, CL/F, CLR, glucose, insulin, glucagon
Frequency of dose-limiting toxicities (DLTs) at each dose level associated with q28 days administration of pasireotide LAR during the first 2 treatment cycles.
in patients with acromegaly and in patients with carcinoid disease
| Arm | Type | Description |
|---|---|---|
| [177Lu]Lu-DOTA-TATE + Octreotide LAR | EXPERIMENTAL | Participants in this arm will receive \[177Lu\]Lu-DOTA-TATE plus Octreotide long-acting release (LAR). |
| Octreotide LAR | ACTIVE_COMPARATOR | Participants in this arm will receive Octreotide LAR only. |
| Pasireotide LAR | EXPERIMENTAL | Patients who qualify for the core phase of the study will be treated with pasireotide LAR 40 mg initially. Patients not achieving biochemical control can be up-titrated to pasireotide LAR 60 mg. |
| 10 mg LAR dose | EXPERIMENTAL | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. |
| 30 mg LAR dose | EXPERIMENTAL | Randomization was stratified based on Screening mUFC to ensure balanced distribution of disease severity in the two dose arms. |
| Pasireotide LAR 40 mg | EXPERIMENTAL | Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) |
| Pasireotide LAR 60 mg | EXPERIMENTAL | Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) |
| Control arm (octreotide or lanreotide) | ACTIVE_COMPARATOR | If a patient is randomized to the open label arm the investigator will either: * be instructed to contact a Novartis delegate to initiate shipment of either octreotide LAR 30 mg or lanreotide ATG 120 mg from a Novartis or designee depot to the site, or * continue to dispense either octreotide LAR 30 mg or lanreotide ATG 120 mg available at the institution to the patient if permitted by local regulations. |
| Pasireotide 600 ug | EXPERIMENTAL | At randomization, participants received 600 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was \<= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 900ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotide was available commercially in their country. |
| Pasireotide 900 ug | EXPERIMENTAL | At randomization, participants received 900 ug subcutaneously (sc) twice daily (bid). Participants continued at this dose until month 6 if their month 3 mean urinary free cortisol (mUFC) was \<= 2 x the upper limit of normal (ULN) and the mUFC was below or equal to their baseline mUFC. Participants not meeting the mUFC criteria at month 3 were unblinded and required to increase their dose to 1200 ug bid on an open label basis. Participants had the option to continue in the extension phase as long as they did not meet any discontinuation criteria or until pasireotide was available commercially in their country. |
| SMS995 | EXPERIMENTAL | - |
| Everolimus | EXPERIMENTAL | Everolimus 10 mg taken orally (p.o) once daily starting on Day 1 |
| Pasireotide LAR and Everolimus Combination | EXPERIMENTAL | Pasireotide LAR 60 mg i.m. injected once every 28 days + Everolimus 10 mg p.o. daily starting on Day 1 |
| SOM230 | EXPERIMENTAL | Subjects with dumping syndrome treated with pasireotide |
| Pasireotide LAR 20mg | EXPERIMENTAL | Enrolled patients were randomized to 20mg pasireotide LAR. |
| Pasireotide LAR 40mg | EXPERIMENTAL | Enrolled patients were randomized to 40mg pasireotide LAR. |
| Pasireotide LAR 60mg | EXPERIMENTAL | Enrolled patients were randomized to 60mg pasireotide LAR. |
| Octreotide | EXPERIMENTAL | Participants received Octreotide long-acting release (LAR) 30 mg intramuscular injection every 28 days for 3 months beginning on Day 1. Participants also received immediate-release Octreotide 600 µg/day (administered subcutaneously 2 or 3 times a day or via continuous intravenous (IV) or subcutaneous injection over a 24 hour period) and methlylpredinisolone 3-4 mg/kg per day (IV bolus for 1 hour or 2 subcutaneous injections) for the first 6 days. |
| Placebo | PLACEBO_COMPARATOR | Participants received physiologic saline solution intramuscular injection every 28 days for 3 months beginning on Day 1. Participants also received physiologic saline solution (administered subcutaneously 2 or 3 times a day or via continuous intravenous or subcutaneous injection over a 24 hour period) and methlylpredinisolone 3-4 mg/kg per day (IV bolus for 1 hour or 2 subcutaneous injections) for the first 6 days. |
| Pasireotide s.c. Overall | EXPERIMENTAL | Participants received pasireotide as a daily subcutaneous (s.c) injection, every 12 hours at 9:00 AM and 9:00 PM at the dose at which the biochemical control was achieved (either 200, 400, or 600 microgram (μg)) for as long as the participant benefited from the treatment, and there were no safety or tolerability concerns (median duration of 22.7 months). |
| Pasireotide 600 μg BID SC or Ramp up Dose 900 μg BID SC | EXPERIMENTAL | Participants received pasireotide 600 micrograms (μg) twice daily (BID) subcutaneously (SC) to achieve or maintain urinary free cortisol (UFC) normalization. If UFC levels were increased at any time, participants received 900 μg BID SC, until no safety or tolerability concerns were observed as per investigators assessment. If the participant was unable to tolerate the 900 μg BID, dosing of 600 μg three times a day was given. |
| Sandostatin s.c. (Octreotide) | EXPERIMENTAL | - |
| Pasireotide (SOM230) | EXPERIMENTAL | - |
| Pasireotide | EXPERIMENTAL | - |
| SOM230 LAR | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| [177Lu]Lu-DOTA-TATE | RADIATION | \[177Lu\]Lu-DOTA-TATE will be administered 4 times during treatment period with frequency of every 8 weeks (Q8W) |
| Octreotide LAR | DRUG | Octreotide LAR will be administered Q8W when co-administered with \[177Lu\]Lu-DOTA-TATE in the investigational arm followed by Q4W. In the control arm Octreotide LAR will be administered Q4W. |
| Pasireotide LAR | DRUG | Pasireotide 40 mg and 60 mg. Pasireotide 20 mg which was allowed for dose decrease in case of adverse event. |
| SOM230 LAR 30 mg | DRUG | starting dose of 30 mg i.m. administered once every 28 days for 4 months, followed by dose up-titration or continuation of starting dose. |
| SOM230 LAR 10 mg | DRUG | starting does of SOM230 LAR 10 mg i.m. administered once every 28 days for 4 months, followed by dose up-titration or continuation of the starting dose. |
| Pasireotide | DRUG | * Double-blind pasireotide LAR 40 mg i.m. injection once every 28 ± 2 days for 24 weeks or * Double-blind pasireotide LAR 60 mg i.m. injection once every 28 ± 2 days for 24 weeks |
| octreotide LAR 30mg | DRUG | In an open-label, active control arm, continue on the same treatment with octreotide LAR 30 mg every 28 ± 2 days as received for at least 6 months prior to randomization |
| lanreotide ATG 120mg | DRUG | In an open-label, active control arm, continue on the same treatment with lanreotide ATG 120 mg every 28 ± 2 days as received for at least 6 months prior to randomization |
| Octreotide | DRUG | Octreotide LAR 40mg i.m. depot injection - Patients may also receive octreotide 100 µg s.c. 3 times a day for symptom control as needed |
| Everolimus | DRUG | 10 mg tables administered orally once a day |
| Pasireotide LAR and Everolimus Combination | DRUG | Pasireotide LAR 60 mg i.m. injected once every 28 days + Everolimus 10 mg p.o. daily |
| SOM230 | DRUG | Pasireotide (SOM230) sc injection was provided as solution for injection in individual 1-point-cut 1 mL ampule, containing nominally 200 μg of pasireotide (as free base). Doses: 50, 100, 150 and 200 μg. Pasireotide im LAR depot injection was provided as micro particles powder in vials containing nominally 10, 20, 40 \& 60 mg of pasireotide (as free base) \& solvent for suspension for injection in ampules for the reconstitution of the LAR micro particles. Doses: 10, 20, 30, 40 or 60 mg |
| Octreotide (Immediate release) | DRUG | Immediate-release Octreotide supplied in 100 µg/mL ampules. |
| methylprednisolone | DRUG | methlylpredinisolone 3-4 mg/kg per day (IV bolus for 1 hour or 2 subcutaneous injections). |
| Placebo | DRUG | Physiologic saline solution |
| Pasireotide (SOM230), Octreotide (Sandostatin) | DRUG | - |
| Pasireotide (SOM230) | DRUG | Open label. Patients received starting dose of 300 µg of study drug subcutaneously (s.c.) twice (total of 600 µg ) daily for three days, which could be increased in 150 µg increments up to 900 µg twice daily (total 1800 µg daily) if control of symptoms was not achieved. Prior sponsor agreement was required for a higher dose. A dose of 2400 µg/day was the maximum allowed. Dose reductions of 300 µg/day were allowed at any time if unacceptable toxicity occurred. |
Inclusion Criteria: * Presence of metastasized or locally advanced, unresectable (curative intent), histologically proven, well differentiated Grade 1 or Grade 2 (Ki-67 \<10%) gastroenteropancreatic neuroendocrine tumor (GEP-NET) diagnosed within 6 months prior to screening. * Participants with hig...
SOM230, also known as pasireotide, is an investigational small molecule being studied for Dumping Syndrome, Castration Resistant Prostate Cancer, and Renal Impairment. It is developed by Novartis AG (NVS) and is in clinical development, with trials completed in these indications.
SOM230 is a somatostatin analog that targets somatostatin receptors. It is being studied for its effects in conditions like Dumping Syndrome and Castration Resistant Prostate Cancer, where it may modulate hormone and growth factor signaling.
SOM230 is developed by Novartis AG, a global healthcare company traded on the NYSE under the ticker NVS. It is an investigational small molecule in clinical development for multiple indications.
SOM230 has completed Phase 1 and Phase 2 clinical trials. It is not approved and remains investigational. Completed trials include a Phase 1 study in Renal Impairment, a Phase 2 study in Dumping Syndrome, and a Phase 1 study in Castration Resistant Prostate Cancer.
SOM230 has completed three clinical trials: NCT01578928, a Phase 1 pharmacokinetic and safety study in subjects with Renal Impairment; NCT01637272, a Phase 2 efficacy and safety study in Dumping Syndrome; and NCT01646684, a Phase 1 safety and preliminary efficacy study in Castration Resistant Prostate Cancer.
Yes, SOM230 is also known as pasireotide. Clinical trials for SOM230, such as NCT01578928 and NCT01637272, refer to pasireotide in their titles, confirming they are the same drug.