Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
avelumab · 6 trials · 7 indications
Overall survival was defined as the time (in months) from the date of randomization to the date of death due to any cause. Participants last known to be alive were censored at date of last contact. Analysis was performed using Kaplan-Meier method.
PFS: time from the date of randomization to the date of the first documentation of progressive disease (PD) according to Response Evaluation Criteria in Solid Tumours (RECIST version \[v\] 1.1) or death due to any cause, whichever occurred first as assessed by BICR. PFS data was censored on date of last adequate tumor assessment for participants who did not have an event (PD or death), who started new anti-cancer therapy prior to an event or for participants with an event after 2 or more missing tumor assessments. PD was defined as at least a 20 percent (%), increase in the sum of all the longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to relative increase of 20 %, sum must have also demonstrated an absolute more than (\>) of at least 5 millimeter (mm). The appearance of one or more new lesions was also considered progression.
OS was defined as the time from the date of randomization to the date of death due to any cause. Participants last known to be alive were censored at date of last contact. Analysis was performed using Kaplan-Meier method.
PFS is defined as the time from date of randomization to the date of the first documentation of progression of disease (PD) or death due to any cause, whichever occurs first. PFS time was summarized by treatment arm using the Kaplan-Meier method. PFS based on BICR assessment was evaluated for this endpoint.
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs were graded by investigator according to NCI CTCAE v.4.03 as follows: Grade 1: mild AE, Grade 2: moderate AE, Grade 3: severe AE, Grade 4: life-threatening consequences and urgent intervention indicated, Grade 5: death related to AE.
As per NCI-CTCAE v 4.03, anemia Grade 1= Less than (\<) lower limit of normal (LLN) to 100 gram per liter (g/L),Grade 2= \<100 to 80 g/L; hemoglobin increased: Grade 1= increase of greater than (\>) 0 to 2 gram per deciliter(g/dL) above upper limit of normal \[ULN\]; lymphocyte count decreased: Grade 1= \<LLN to 0.8\*10\^9/L, Grade 2= \<0.8\*10\^9/L to 0.5\*10\^9/L, Grade 3= \<0.5\*10\^9/L to 0.2\*10\^9/L ; lymphocyte count increased: Grade 2= \>4\*10\^9/L to 20\*10\^9/L; neutrophil count decreased: Grade 1= \<LLN to 1.5\*10\^9/L ,Grade 2= \<1.5\*10\^9/L to 1.0\*10\^9/L; platelet count decreased: Grade 1= \<LLN to 75.0\*10\^9/L, Grade 2= \<75.0\*10\^9/L to 50.0\*10\^9/L; white blood cell decreased: Grade 1= \<LLN to 3\*10\^9/L, Grade 2= \<3\*10\^9/L to 2\*10\^9/L.
ALT,ALP,AST increased grades(g):g1\>ULN-3.0\*ULN,g2\>3.0-5.0\*ULN,g3\>5.0-20.0\*ULN; blood bilirubin increased:g1\>ULN-1.5\*ULN, g2\>1.5-3.0\*ULN, g3\>3.0-10.0\*ULN; \[cholesterol high:g1\>ULN-7.75, g2 \>7.75-10.34,g4 \>12.92\]millimoles per liter(mmol/L);creatine phosphokinase, gamma-glutamyl transferase(ggt) increased g1\>ULN-2.5\*ULN, g2\>2.5\*ULN-5\*ULN; Ggt increased g3 \>5.0-20.0\*ULN; Creatinine increased: g1\>ULN-1.5\*ULN; \[hypoalbuminemia:g1\<LLN-30,g2\<30-20\] grams per liter(g/L);\[hyperglycemia:g1\> ULN-8.9,g2\> 8.9-13.9,g3\> 13.9-27.8;hypermagnesemia:g1\>ULN-1.23;hypercalcemia:g1\>ULN -2.9;hyperkalemia:g1\>ULN-5.5,hypernatremia:g1\>ULN-150;hypertriglyceridemia g1:1.71-3.42,g2 \>3.42-5.7;hypocalcemia:g1\<LLN-2.0,hypoglycemia:g1\<LLN-3.0, g2\<3.0-2.2;hypokalemia:g2\<LLN-3.0,g4\<2.5,hypomagnesemia:g1\<LLN-0.5,hyponatremia:g1\<LLN-130, g3\<130-120,hypophosphatemia:g1\<LLN-0.8,g2\<0.8-0.6\]mmol/L;lipase increased:g1\>ULN-1.5\*ULN,g3 \>2.0-5.0\*ULN;serum amylase increased:g1\>ULN-1.5\*ULN, g2\>1.5-2.0\*ULN,g3\>2.0-5.0\*ULN.
DLT: greater than or equal to (\>=) Grade 3 hematologic/non-hematologic toxicity, Grade 3-4 liver-related laboratory test elevation (alanine aminotransferase, aspartate aminotransferase) with Grade 2 elevation of total bilirubin, non-hematologic Grade 3 laboratory abnormality (required medical intervention to treat participant/led to hospitalization), inability to complete \>=75% of first 2 cycles doses of axitinib (from Cycle 1 Day 1 after completion of lead-in period) or 2 infusions of avelumab within DLT observation period due to investigational product related toxicity.
| Arm | Type | Description |
|---|---|---|
| Arm 1 | EXPERIMENTAL | Avelumab monotherapy as specified by sub-study protocol B9991001C |
| Arm 2 | EXPERIMENTAL | Avelumab in combination with CMP 001, Utomilumab or PF04518600 as specified by sub-study protocol B9991004C |
| Arm 3 | EXPERIMENTAL | Avelumab in combination with Loratanib as specified by sub-study protocol B9991005C |
| Arm 4 | EXPERIMENTAL | Avelumab monotherapy as specified by sub-study protocol B9991009C |
| Arm 5 | EXPERIMENTAL | Avelumab monotherapy or in combination with Pemetrexed as specified by sub-study protocol B9991023C |
| Arm 6 | EXPERIMENTAL | Avelumab in combination with Talazoparib as specified by sub-study B9991025C. |
| Arm 7 | EXPERIMENTAL | Avelumab in combination with Axitinib as specified by sub-study B9991027C. |
| Arm 8 | EXPERIMENTAL | Avelumab in combination with Talazoparib as specified by sub-study B9991032C. |
| Arm 9 | EXPERIMENTAL | Avelumab in combination with Axitinib as specified by sub-study protocol B9991003C |
| Arm A | EXPERIMENTAL | Avelumab plus Best Supportive Care (BSC) |
| Arm B | OTHER | Best Supportive Care (BSC) alone Following the planned interim analysis for this study, eligible patients in Arm B whose cancer has not worsened and are still in the "watch and wait" part of the study will be given the option to receive Avelumab plus BSC. Prior to this, Arm B patients received BSC alone. All patients who choose not to receive Avelumab will be discontinued. |
| Avelumab in combination with axitinib | EXPERIMENTAL | Avelumab administered at 10 mg/kg IV every two weeks in combination with axitinib, 5 mg PO BID. |
| Sunitinib | ACTIVE_COMPARATOR | Sunitinib given at 50 mg PO QD on schedule 4/2 |
| avelumab | EXPERIMENTAL | Arm A: avelumab alone |
| avelumab plus pegylated liposomal doxorubicin (PLD) | EXPERIMENTAL | Arm B: avelumab plus PLD |
| PLD | ACTIVE_COMPARATOR | Arm C: PLD alone |
| Experimental 1 | EXPERIMENTAL | Avelumab (MSB0010718C) in combination with axitinib (AG-013736) |
| Dose finding phase and dose expansion phase. | EXPERIMENTAL | To test the maximum tolerated dose of avelumab (MSB0010718C) in combination with axitinib (AG-013736) |
| Name | Type | Description |
|---|---|---|
| Avelumab | DRUG | oral |
| Lorlatanib | DRUG | oral |
| Talazoparib | DRUG | oral |
| Pemetrexed | DRUG | IV (intravenous) infusion |
| Axitinib | DRUG | oral |
| CMP 001 | DRUG | IT (intratumoral) or SC (subcutaneous) |
| Utomilumab | DRUG | IV infusion |
| PF04518600 | DRUG | IV infusion |
| Best Supportive Care | OTHER | BSC will be administered as deemed appropriate by the treating physician, and could include treatment with antibiotics, nutritional support, correction of metabolic disorders, optimal symptom control and pain management (including palliative radiotherapy), etc. BSC does not include any active anti-tumor therapy, however local radiotherapy of isolated lesions with palliative intent is acceptable. |
| Following the planned interim analysis for this study: Avelumab | BIOLOGICAL | 1 hour intravenous infusion every 2 weeks (Q2W) in 4 week cycles |
| Avelumab (MSB0010718C) | DRUG | IV treatment Avelumab administered at 10 mg/kg IV every two weeks |
| Axitinib (AG-013736) | DRUG | Oral treatment Axitinib given 5 mg PO BID |
| Sunitinib | DRUG | Oral treatment Sunitinib given at 50 mg PO QD on schedule 4/2 |
| PLD | DRUG | PLD (Arm B, Arm C) 40 mg/m2 will be given as a 1 hour IV infusion every 4 weeks (Q4W) in 4 week cycles |
Inclusion Criteria: 1. Any participant who is receiving study treatment and deriving significant clinical benefit or is in the safety and/or survival follow-up period in a Pfizer-sponsored Avelumab Parent Study. 2. Participants must agree to follow the reproductive criteria. 3. Participants must be...
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