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Also known as AZD6094, [11C]savolitinib, HMPL - 504
Savolitinib · 10 trials · 15 indications
Defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause.
Defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause. The analysis will include all randomised participants as randomised, regardless of whether the participant withdraws from therapy, receives another anti-cancer therapy or clinically progresses prior to RECIST 1.1 progression.
Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Progressive Disease (PD): \>= 20% increase in the sum of diameters of TLs and an absolute increase in sum of diameters of \>=5mm (compared to the previous minimum sum) or progression of NTLs or a new lesion. PFS is the time from date of randomisation until the date of PD (defined by Recist 1.1 and confirmed by BICR) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from randomised therapy or received another anti-cancer therapy prior to progression.
PFS (Progression-Free Survival ) will be defined as the time from first dose of study intervention until progression per RECIST 1.1 as assessed by the investigator or death due to any cause prior to progressive disease.
The primary outcome measure was Objective Response Rate (ORR), defined as the proportion of patients with either a complete response or a partial response by investigator assessment according to Response Evaluation Criteria for Solid Tumours (RECIST) v1.1.
The primary outcome measure was ORR, defined as the proportion of patients with either a complete response or a partial response by investigator assessment according to RECIST v1.1.
The primary outcome measure was ORR, defined as the proportion of patients with either a confirmed complete response/partial response by investigator assessment according to RECIST v1.1.
To assess the effect of savolitinib on the PK of midazolam.
To assess the effect of savolitinib on the PK of midazolam.
Cmax ratio of test treatment (savolitinib+famotidine) relative to reference treatment (savolitinib alone) to assess effect of the gastric acid modifier, famotidine, on the PK of savolitinib.
AUC ratio of test treatment (savolitinib+famotidine) relative to reference treatment (savolitinib alone) to assess effect of the gastric acid modifier, famotidine, on the PK of savolitinib.
To assess the effect of itraconazole on the PK of savolitinib
To assess the effect of itraconazole on the PK of savolitinib
To assess the effect of rifampicin on the PK of savolitinib
To assess the effect of rifampicin on the PK of savolitinib
To assess the effect of AZD6094 at single therapeutic dose (600mg) on ventricular repolarization by assessing the time matched baseline-adjusted, placebo subtracted QTc interval corrected for RR (R waves on electrocardiogram \[ECG\]) by the Fridericia formula (QTcF). The ECGs -digital (dECG) and page (pECG) would be recorded during the study for the assessment of safety. Paper ECG for safety review will be performed following the dECG recordings and at additional intervals if required.
| Arm | Type | Description |
|---|---|---|
| Chemotherapy | ACTIVE_COMPARATOR | Pemetrexed (500 mg/m2) with either cisplatin (75 mg/m2) or carboplatin (AUC5) on Day 1 of 21-day cycles (Q3W) for 4 cycles, followed by pemetrexed maintenance (500 mg/m2) Q3W |
| Savolitinib + Osimertinib | EXPERIMENTAL | 300 mg savolitinib BID plus 80 mg osimertinib QD |
| Arm A | EXPERIMENTAL | savolitinib 600mg plus durvalumab 1500mg |
| Arm B | ACTIVE_COMPARATOR | sunitinib 50mg |
| Arm C | EXPERIMENTAL | durvalumab 1500mg |
| Savolitinib | EXPERIMENTAL | See: intervention description |
| Sunitinib | ACTIVE_COMPARATOR | See: intervention description |
| Savolitinib combine with Durvalumab | EXPERIMENTAL | single-arm |
| AZD6094 600 mg daily continuously | EXPERIMENTAL | All patients entering the study will take AZD6094 600 mg by mouth (PO) once daily (QD). Treatment will be given continuously. |
| Midazolam + Savolitinib | EXPERIMENTAL | * Treatment Period 1: Single administration of midazolam (1 mg) will occur on Study Day 1, after a high fat, high calorie breakfast, followed by PK sampling for 24 hours. * Treatment Period 2: Single administration of midazolam 1 mg in combination with a single administration of savolitinib (600 mg), after a high fat, high calorie breakfast will occur on Study Day 5 and PK sampling will occur for 24 hours. |
| Savolitinib + Famotidine | EXPERIMENTAL | Subjects will receive savolitinib 600mg single dose after high-fat, high-calorie meal and after 1.5 hours (Part A) or 5.5 hours (Part B) of famotidine 40mg dose. Famotidine will be administered after an overnight fast of at least 8 hours with approximately 240 mL of water. |
| Savolitinib and/or Itraconazole | EXPERIMENTAL | Treatment Period 1: Single administration of savolitinib (200 mg) will occur on Study Day 1 after a high-fat, high-calorie breakfast followed by PK sampling for 48 hours Treatment Period 2: Itraconazole will be administered (200 mg BID) on Study Day 15, and (200 mg QD) on Study Days 16 and 17, 1 hour before breakfast (and before dinner, when applicable) Treatment Period 3: A single combination of itraconazole (200 mg) 1 hour before breakfast + savolitinib (200 mg) after a high-fat, high-calorie breakfast on Study Day 18, and a single dose of itraconazole (200 mg) on Study Day 19, 1 hour before breakfast |
| Savolitinib and/or Rifampicin | EXPERIMENTAL | Treatment Period 1 consists of 16 days starting with admission on Study Day -1, followed by a single dose administration of savolitinib on Day 1, followed by a washout period of at least 14 days. Subjects will be discharged from the Study Centre on Study Day 3, after the last PK sample is collected Treatment Period 2 consists of 6 days, starting with admission on Study Day 14, followed by QD dose administrations of rifampicin for 5 consecutive days (Study Day 15 to Study Day 19) Treatment Period 3 consists of 4 days, starting immediately after Treatment Period 2, comprising of a single dose administration of savolitinib on Study Day 20 and QD dose administration of rifampicin on Study Day 20 and Study Day 21. Subjects will be discharged from the Study Centre on Study Day 22, after the last PK sample is collected |
| Cohort 1 | EXPERIMENTAL | Participants will receive orally single dose of study drugs in the sequence of ABC. A - AZD6094 600 mg (3X 200 mg tablet) B - Placebo C - Moxifloxacin 400 mg |
| Cohort 2 | EXPERIMENTAL | Participants will receive orally single dose of study drugs in the sequence of ACB. A - AZD6094 600 mg (3X 200 mg tablet) B - Placebo C - Moxifloxacin 400 mg |
| Cohort 3 | EXPERIMENTAL | Participants will receive orally single dose of study drugs in the sequence of BAC. A - AZD6094 600 mg (3X 200 mg tablet) B - Placebo C - Moxifloxacin 400 mg |
| Cohort 4 | EXPERIMENTAL | Participants will receive orally single dose of study drugs in the sequence of BCA. A - AZD6094 600 mg (3X 200 mg tablet) B - Placebo C - Moxifloxacin 400 mg |
| Cohort 5 | EXPERIMENTAL | Participants will receive orally single dose of study drugs in the sequence of CAB. A - AZD6094 600 mg (3X 200 mg tablet) B - Placebo C - Moxifloxacin 400 mg |
| Cohort 6 | EXPERIMENTAL | Participants will receive orally single dose of study drugs in the sequence of CBA. A - AZD6094 600 mg (3X 200 mg tablet) B - Placebo C - Moxifloxacin 400 mg |
| Name | Type | Description |
|---|---|---|
| Savolitinib | DRUG | 300 mg savolitinib (3 × 100 mg tablets twice daily) Administrative route : oral |
| Osimertinib | DRUG | 80 mg osimertinib (1 × 80 mg tablet once daily) Administrative route : oral |
| Pemetrexed | DRUG | Pemetrexed (500 mg/m2) Administrative route : IV infusion |
| Cisplatin | DRUG | Cisplatin (75 mg/m2) Administrative route : IV infusion |
| Carboplatin | DRUG | Carboplatin (AUC5) Administrative route : IV infusion |
| durvalumab | DRUG | Concentrate for solution for IV infusion : 1500 mg durvalumab every 4 weeks |
| sunitinib | DRUG | Capsules : 2 x 25mg capsules once daily 4 weeks on, 2 weeks off |
| AZD6094 | DRUG | AZD6094 is a potent and selective small molecule mesenchymal epithelial transition (c-MET) kinase inhibitor. |
| Midazolam | DRUG | Single dose (alone) on Study Day 1 and single dose (together with savolitinib) on Study Day 5, both after a high fat, high calorie breakfast. |
| Famotidine | DRUG | Subjects will receive famotidine tablet 40mg orally after an overnight (minimum 8hours) of fasting. |
| Itraconazole | DRUG | Twice daily on first day of dosing (Study Day 15) followed by once daily for 4 days (Study Day 16 - Study Day 19) administered 1 hour before any breakfast (and 1 hour before dinner on Study Day 15) |
| Rifampicin | DRUG | Patients will receive Rifampicin once daily on Study Day 15, 16, 17, 18, 19, 20 and 21. Rifampicin will be administered 1 hour before breakfast. |
| AZD6094 200 mg | DRUG | A potent and selective small molecule mesenchymal epithelial transition (MET) kinase inhibitor with significant antitumor activity. |
| Placebo | OTHER | AZD6094 matching placebo without any pharmacological activity. |
| Moxifloxacin | DRUG | A fluoroquinolone broad-spectrum antibiotic, produces a mild, but reproducible increase in QT interval corrected (QTc) in healthy normal participants at time to reach maximum concentration (tmax - approximately 2 hours (0.5 to 4 hours)). This effect is close to the ECG interval measured from the onset of the QRS complex (onset of the QRS complex to the J point) to the offset of the T wave (QT)/QTc effect that represents the threshold of regulatory concern, around 5 ms mean QTc interval prolongation. |
Inclusion Criteria: * Provision of signed and dated written ICF prior to any mandatory and non-mandatory study-specific procedures, sampling and analyses. * Participant must be ≥18 years (≥ 19 years of age in South Korea) at the time of signing the informed consent. All genders are permitted. * His...
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Savolitinib is an investigational oral medicine being studied in oncology for non-small cell lung cancer, papillary renal cell carcinoma, and other solid tumors. It is being developed both as a single agent and in combination with other therapies such as osimertinib and durvalumab. It is not yet approved for commercial use.
Savolitinib targets MET, a receptor tyrosine kinase. It is a small-molecule inhibitor that blocks MET signaling, which is relevant in tumors where the MET pathway drives growth. Trials are biomarker-selected, meaning patients are chosen based on MET-related characteristics.
Savolitinib is being developed by AstraZeneca PLC, which trades under the ticker AZN. AstraZeneca sponsors the clinical program, including the Phase 3 trials in lung cancer and papillary renal cell carcinoma.
Savolitinib is in Phase 3 clinical development. The program includes Phase 3 trials in non-small cell lung cancer and papillary renal cell carcinoma, as well as earlier-phase studies. It remains investigational and has not been approved by the FDA.
Savolitinib is being studied in several trials, including NCT05261399, a Phase 3 study of savolitinib plus osimertinib versus platinum-based chemotherapy in NSCLC that has progressed on osimertinib; NCT05043090, a Phase 3 trial in MET-driven papillary renal cell carcinoma; and NCT05374603, a Phase 2 study with durvalumab in EGFR wild-type NSCLC.
Yes, savolitinib is also known as AZD6094. Other names used in study records include AZD6094 200 mg, [11C]savolitinib, and [14C] AZD6094 oral solution. These refer to the same investigational MET inhibitor developed by AstraZeneca.