Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Avelumab · 8 trials · 8 indications
Overall Survival was defined as the time from randomization to the date of death due to any cause. For participants who were still alive at the time of data analysis or who were lost to follow-up, OS time was censored at the date of last contact. OS was measured using Kaplan-Meier (KM) estimates.
The primary clinical objective is to determine the efficacy of a standard 1st-line regimen (FOLFIRI plus cetuximab) in patients with RAS wild-type mCRC with Avelumab mainte-nance in terms of progression free survival rate after 8 months (according to RECIST 1.1).
Confirmed BOR was defined as the percentage of participants who achieved confirmed complete responses (CR) or partial response (PR), according to RECIST version 1.1 assessed by the Investigator.CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)= Neither sufficient increase to qualify for progression of disease (PD) nor sufficient shrinkage to qualify for PR. PD: At least a 20 % increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. Confirmed CR=as at least two determinations of CR at least 4 weeks apart with no PD. Confirmed PR=as at least 2 determinations of PR or better (PR followed by PR or PR followed by CR), at least 4 weeks apart (not qualifying for a CR) with no PD in between. Percentage of Participants with confirmed BOR were reported.
\- Outcome measure: Pathological complete response is defined as the absence of invasive carcinoma (ypT0/Tis) disease and the absence of microscopic lymph node metastases (ypN0) on the final surgical specimen.
Safety run-in: dose-limiting toxicities (DLT) will be determined during the first 3 months after the start of treatment
The main endpoint of this study is the rate of patients with successful normalization of hCG allowing for treatment discontinuation (hCG normalization). Patients will continue on treatment until the weekly hCG assays reach the institutional normal threshold, and then for 3 additional cycles, or otherwise will be stopped in the case of resistance, defined as a rise (a \> 20% rise between two assays, observed twice on three consecutive weekly assays) or a plateau (a \< 10% decrease between two assays observed three times on four consecutive weekly assays) in the hCG level, or unacceptable toxicity and/or death.
The overall response rate will be defined as the number of participants with confirmed complete response or partial response (CR or PR) recorded as the best response over the study period, divided by the number of participants evaluable for response as defined by RECIST version 1.1.
according to CTC 4.03
Immune-related toxicity which requires discontinuation of Avelumab
| Arm | Type | Description |
|---|---|---|
| Chemotherapy + Best Supportive Care (BSC) | EXPERIMENTAL | In Maintenance Phase, participants continued the same regimen of oxaliplatin-fluoropyrimidine doublet chemotherapy (oxaliplatin + 5FU/LV or oxaliplatin + capecitabine) as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation. Participants who were not deemed eligible to receive chemotherapy at the dose and schedule specified above received BSC alone once every 3 weeks. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on Investigator's discretion. |
| Avelumab | EXPERIMENTAL | In Maintenance phase, participants received avelumab as a 1-hour intravenous (IV) infusion at 10 milligrams per kilogram (mg/kg) once every 2-week treatment cycle until progressive disease or unacceptable toxicity or discontinuation. |
| RAS wild-type Avelumab | OTHER | Induction therapy: FOLFIRI 5-FU: 400 mg/m2 (i.v. bolus) Folinic acid: 400mg/m2 Irinotecan: 180 mg/m2 5-FU: 2.400 mg/m2 (i.v. 46h) Cetuximab 400 mg/m2 i.v. 120min initial dose 250 mg/m2 i.v. 60min q 1w Maintenance therapy: Avelumab 10mg/kg IV (day 1 q2w) |
| Avelumab and Cetuximab | EXPERIMENTAL | Participants received 800 milligrams Avelumab, 1250 milligrams per square meter (mg/m\^2) gemcitabine on Day 1 and Day 8, cisplatin at a dose of 75 mg/m\^2 on Day 1 along with 250 mg/m2 body surface area Cetuximab on Day 1 and 500 mg/m2 body surface area on Day 8 of each cycle as intravenous (IV) infusions up to maximum of 4 cycles (each cycle is of 3 weeks) until disease progression or unacceptable toxicities. In case of cisplatin toxicities, participants were switched to carboplatin at a dose of target area under the serum concentration-time curve of 5 (AUC 5) on Day 1 for the remainder of cycles. Subsequently participants were administered with avelumab and cetuximab as IV infusion at the dose of 800 mg and 500 mg/m\^2 respectively, every 2 weeks in the Maintenance phase until disease progression or unacceptable toxicities. |
| DD-MVAC + avelumab | EXPERIMENTAL | Methotrexate, vinblastine, doxorubicin and cisplatin (DD-MVAC) given in combination with Avelumab. DD-MVAC consists of Methotrexate 30 mg/m2 iv day 1, Vinblastine 3 mg/m2 iv day 2, Cisplatin 70 mg/m2 iv day 2 and Doxorubicin 30 mg/m2 iv day 2. Each cycle is given every 2 weeks for a maximum of 4 administrations Chemotherapy is associated with Avelumab 10 mg/kg, 1-hour intravenous (iv) infusion, given on day 2 every 2 weeks. Cystectomy will be performed 3 to 6 weeks after last administration of chemotherapy |
| CG+ avelumab | EXPERIMENTAL | Cisplatin, gemcitabine (CG) consists of Gemcitabine 1000 mg/m2 iv in day 1 and day 8 and Cisplatin 70 mg/m2 iv in day 1. Each cycle is given every 3 weeks for a maximum of 4 administrations. Chemotherapy is associated with Avelumab 10 mg/kg, 1-hour intravenous (iv) infusion, given on day 1 every 2 weeks Cystectomy will be performed 3 to 6 weeks after last administration of chemotherapy |
| PG+ avelumab | EXPERIMENTAL | Paclitaxel, gemcitabine (PG) consists of Paclitaxel 80 mg/m2 iv in day 1 and day 15 and Gemcitabine 1000 mg/m2 iv in day 1 and day 15. Each cycle is repeated every 3 weeks for a maximum of 4 administrations. Chemotherapy is associated with Avelumab 10 mg/kg, 1-hour intravenous (iv) infusion, given on day 1 every 2 weeks Cystectomy will be performed 3 to 6 weeks after last administration of chemotherapy |
| Avelumab combined with methotrexate and folinic acid | EXPERIMENTAL | Avelumab administration at 800 mg every 2 weeks and methotrexate administration at 1mg/kg/day during 4 months ½ (median) |
| Intervention Arm | EXPERIMENTAL | Treatment with avelumab |
| Bioimmunoradiotherapy | EXPERIMENTAL | Concurrent Radiation therapy (i.e. 5 times a week, 7 weeks, total dose 70 Gy) with cetuximab (loading dose 400 mg/m2 i.v. day -7, 250 mg/m2 i.v weekly wk 1-7) and Avelumab10 mg/kg i.v. at day -7, 7, 21,35 + maintenance therapy i.e avelumab10 mg/kg i.v. every 2 weeks for 6 months (wk 8,10, 12, 14, 16, 18, 20, 22, 24, 26. |
| Open-label | OTHER | Avelumab - Single-arm open label study |
| Name | Type | Description |
|---|---|---|
| Avelumab | DRUG | Maintenance Phase: Intravenous (IV) infusion (10 mg/kg over 1 hour) once every 2 weeks. |
| Oxaliplatin | DRUG | Induction Phase: Oxaliplatin was administered at a dose of 85 mg per square meter (mg/m\^2) as a continuous intravenous (IV) infusion on Day 1 along with leucovorin followed by 5-Fluorouracil every 2 weeks up to 12 weeks (or) Oxaliplatin at 130 mg/m\^2 IV on Day 1 along with capecitabine twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks up to 12 weeks. Maintenance Phase: Participants were continued the same regimen of chemotherapy as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation. |
| 5-Fluorouracil | DRUG | Induction Phase: 5-Fluorouracil was administered at a dose of 2600 mg/m\^2 IV continuous infusion over 24 hours on Day 1 (or) 5-FU at 400 mg/m\^2 IV push on Day 1 and 2400 mg/m\^2 IV continuous infusion over 46-48 hours (Days 1 and 2) along with oxaliplatin and leucovorin every 2 weeks up to 12 weeks. Maintenance Phase: Participants were continued the same regimen of chemotherapy as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation. |
| Leucovorin | DRUG | Induction Phase: Leucovorin was administered at a dose of 200 mg/m\^2 IV (or) Leucovorin 400 mg/m\^2 IV on Day 1 along with oxaliplatin and 5-FU every 2 weeks up to 12 weeks. Maintenance Phase: Participants were continued the same regimen of chemotherapy as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation. |
| Capecitabine | DRUG | Induction Phase: Capecitabine was administered at a dose of 1000 mg/m\^2 twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks along with oxaliplatin up to 12 weeks. Maintenance Phase: Participants were continued the same regimen of chemotherapy as they received during the Induction Phase every 3 weeks until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation. |
| Best supportive care | OTHER | Treatment administered with the intent to maximize Quality of Life (QoL) without a specific antineoplastic regimen. These may include for example antibiotics, analgesics, antiemetics, thoracentesis, paracentesis, blood transfusions, nutritional support (including jejunostomy), and focal external-beam radiation for control of pain, cough, dyspnea, or bleeding. Best supportive care were administered per institutional guidelines and participants were visit the clinic every 3 weeks. |
| 5-FU | DRUG | 400 mg/m2 (i.v. bolus) 2400 mg/m2 (i.v. 46h) |
| Folinic Acid | DRUG | 400mg/m2 |
| Irinotecan | DRUG | 180 mg/m2 |
| Cetuximab | DRUG | 400 mg/m2 i.v. 120min initial dose 250 mg/m2 i.v. 60min q 1w |
| Gemcitabine | DRUG | Participants received gemcitabine intravenous infusions at a dose of 1250 mg/m\^2 body surface area on Day 1 and Day 8 in 3-week cycles up to a maximum of 4 cycles, until disease progression or unacceptable toxicities. |
| Cisplatin | DRUG | Participants received cisplatin intravenous infusions at a dose of 75 mg/m\^2 body surface area on Day 1 of 3-week cycles up to a maximum of 4 cycles, until disease progression or unacceptable toxicities. |
| Carboplatin | DRUG | In case of cisplatin toxicities, participants were switched to carboplatin at a dose of target area under the serum concentration-time curve of 5 (AUC 5) on Day 1 for the remainder of cycles. |
| cystectomy | PROCEDURE | Cystectomy 3 to 6 weeks after last administration of chemotherapy |
| CG | COMBINATION_PRODUCT | Chemotherapy 4 cycles of 3 weeks |
| DD-MVAC | COMBINATION_PRODUCT | Chemotherapy 4 cycles of 2 weeks |
| PG | COMBINATION_PRODUCT | Chemotherapy 2 cycles of 4 weeks |
| Avelumab Injection | DRUG | Avelumab administration at 800mg a 1 hour IV infusion once every 14 days during 4 months ½ (median) |
| Methotrexate 1 GM Injection | DRUG | methotrexate administration at 1mg/kg/day during 4 months ½ (median) |
| radiotherapy | RADIATION | 5 times a week, 7 weeks, total dose 70 Gy |
Inclusion Criteria: * Male or female participants greater than or equal to (\>=) 18 years * Disease must be measurable by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) * Participants with histologically confirmed unresectable locally advanced or metastatic adenocarcinoma of ...