Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication ERBITUX ® is an epidermal growth factor receptor (EGFR) antagonist indicated for treatment of: Head and Neck Cancer Locally or regionally advanced squamous cell carcinoma of the head and neck in combination with radiation therapy. ( 1.1 , 14.1 ) Recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck in combination with platinum-based therapy with fluorouracil. FDA label
Also known as Erbitux, C225
Cetuximab · 19 trials · 15 indications
PFS time was defined as the time in months from the date of randomization until first observation of PD (based on imaging as assessed by IRC), or death due to any cause when death occurs within 60 days after the last tumor assessment or randomization (whichever is later). PD is defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on trial; and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 millimeter. PFS was measured using Kaplan-Meier (KM) estimates.
PFS was defined as the duration (in months) from randomization until the first progressive disease (PD) observation as assessed by the Independent Review Committee (IRC) according to Response Evaluation Criteria for Solid Tumors (RECIST) version 1.0, or death due to any cause when death occurred within 90 days of randomization or the last tumor assessment, whichever was later. PD was defined as at least a 20% increase in the sum of longest diameter (LD) of the target lesions, taking as references the smallest sum LD since the treatment started (including baseline), or appearance of one or more new lesions, and/or unequivocal progression of existing non-target lesions.
BOR: Percentage of participants experiencing a Complete Response (CR) (complete disappearance of measurable and evaluable disease without new lesions) or Partial Response (PR) (greater than or equal to 50 percent decrease of sum of product diameters of measurable disease, evaluable disease not worsening or progressing, no new lesions confirmed by a subsequent assessment no less than 28 days after criteria for response were first met) (based on modified World Health Organization \[WHO\] criteria), divided by the number of participants belonging to intention to treat (ITT) or safety population.
BOR: Percentage of participants experiencing a CR (complete disappearance of measurable and evaluable disease without new lesions) or PR (greater than or equal to 50 percent decrease of sum of product diameters of measurable disease, evaluable disease not worsening or progressing, no new lesions confirmed by a subsequent assessment no less than 28 days after criteria for response were first met) (based on modified WHO criteria), divided by the number of participants belonging to ITT or safety population.
Best overall (objective) response was defined as the occurrence of complete response (CR) or partial response (PR) based on the investigator's assessment according to modified World Health Organization (WHO) criteria confirmed at a repeat assessment performed no less than 28 days after the criteria for response were first met. CR was defined as disappearance of all index lesions. PR was defined as a 50% or more decrease in the sum of the products of diameters (SOPD) of index lesions compared to the baseline SOPD, with no evidence of PD.
The OS time is defined as the time from trial inclusion to death. Participants without event are censored at the last date known to be alive or at the clinical cut-off date, whichever is earlier.
The OS time is defined as the time from trial inclusion to death. Participants without event are censored at the last date known to be alive or at the clinical cut-off date, whichever is earlier. Percentage of participants who were still alive until one year after the last participant was included (March 2010).
The PFS time is defined as the duration from randomization to either first observation of progressive disease (PD) or occurrence of death due to any cause within 60 days of the last tumor assessment or randomization. Participants without event are censored on the date of last tumor assessment.
Time from randomization to death. Patients without event are censored at the last date known to be alive or at the clinical cut-off date, whatever is earlier.
Duration from randomization until radiological progression (based on modified World Health Organisation (WHO) criteria) or death due to any cause. Only deaths within 60 days of last tumor assessment are considered. Patients without event are censored on the date of last tumor assessment.
Duration from randomization until radiological progression (based on modified WHO criteria) or death due to any cause. Only deaths within 60 days of last tumor assessment are considered. Patients without event are censored on the date of last tumor assessment.
Duration from randomization until radiological progression (based on modified WHO criteria) or death due to any cause. Only deaths within 60 days of last tumor assessment are considered. Patients without event are censored on the date of last tumor assessment.
A precise estimate (+/- 10%) of the probability of not having progression at 9 months. This measure is an estimation derived from the Kaplan-Meier algorithm and does not represent a dimple percentage of participants.
The confirmed overall response rate (cORR) is the percentage of confirmed responses, defined as complete response (CR) or partial response (PR), as assessed by local radiologist/investigator review based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR): Disappearance of all target lesions; Partiel response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Overall Response (OR) = CR + PR.
DLT rate was estimated based on data from DLT-evaluable participants during the DLT-evaluation period (which is the first 28 days after the first dose of study intervention in the SLI) to assess the safety and tolerability of the doublet arm.
PFS was defined as the time from the date of randomization to the earliest documented disease progression (PD) as determined by BICR assessment per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death due to any cause.
PFS was defined as the time from the date of randomization to the earliest documented disease progression as determined by BICR assessment per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death due to any cause.
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).
The best overall response rate is defined as the percentage of participants having achieved confirmed complete response plus partial response as the best overall response according to radiological assessments (based on Response Evaluation Criteria in Solid Tumors version 1.0 \[RECIST v 1.0\] criteria).
Percentage of participants experiencing a complete response \[CR\] (complete disappearance of measurable and evaluable disease without new lesions) or partial response \[PR\] (greater than or equal to 50 percent decrease in the sum of the products of diameters \[SOPD\] of index lesions compared to the baseline SOPD, with no evidence of PD) confirmed by a subsequent assessment no less than 28 days after criteria for response were first met based on modified WHO criteria as assessed by Independent Review Committee (IRC).
Number of subjects who complete ≥70% of Cetuximab planned dose administration in terms of relative dose intensity of Cetuximab and full dose of RT ≤2 weeks over planned schedule in terms of RT duration ≤8 weeks, divided by the the number of subjects in the ITT/Safety population
Response rate was defined as the percentage of subjects with BORR (confirmed complete response \[CR\] or partial response \[PR\]) according to Response Evaluation Criteria in Solid Tumors (RECIST version 1.0) criteria. As per RECIST v 1.0 criteria for target lesions and assessed by magnetic resonance imaging (MRI): CR = disappearance of all target lesions; PR = at least 30 percent (%) decrease in the sum of the longest diameter of target lesions. Response rate will be assessed every 8 weeks.
| Arm | Type | Description |
|---|---|---|
| Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil | EXPERIMENTAL | - |
| Cisplatin/Carboplatin + 5-Flurouracil | ACTIVE_COMPARATOR | - |
| Cetuximab + FOLFOX-4 | EXPERIMENTAL | Subjects received cetuximab in combination with FOLFOX-4 chemotherapy regimen. FOLFOX-4 chemotherapy regimen consists of a combination of oxaliplatin with 5-fluorouracil (5-FU)/folinic acid (FA). Cetuximab was always administered every 7 days with an initial dose of 400 milligram per square meter (mg/m\^2) at 5 milligram per minute (mg/min) and 250 mg/m\^2 at 10 mg/min for subsequent infusions, followed by oxaliplatin 85 mg/m\^2 infused over 120 minutes at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin, FA was administered at a dose of 200 mg/m\^2 infused over 120 minutes, on Day 1, Day 2, and every 2 weeks and then 5- FU was administered as a bolus of 400 mg/m\^2/day intravenously over 2-4 minutes followed by 600 mg/m\^2/day infused over 22 hours, on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity. |
| FOLFOX-4 | ACTIVE_COMPARATOR | Subjects received FOLFOX-4 chemotherapy regimen that consists of a combination of oxaliplatin with 5-FU/FA. Oxaliplatin 85 mg/m\^2 infused over 120 minutes was administered first or simultaneously with FA at a dose of 200 mg/m\^2 infused over 120 minutes on Day 1, Day 2, and every 2 weeks and then 5-FU was administered as a bolus of 400 mg/m\^2/day intravenously over 2-4 minutes followed by 600 mg/m\^2/day infused over 22 hours on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity. |
| Cetuximab + Cisplatin + 5-Fluorouracil (5-FU) | EXPERIMENTAL | - |
| Cetuximab | EXPERIMENTAL | All eligible subjects will receive cetuximab treatment only during week 1 of the treatment course and concomitant cetuximab and boost radiotherapy (RT) during week two to week seven of the treatment course |
| Cetuximab 250 mg/m^2 q1w + Platinum-based Doublet Chemotherapy | ACTIVE_COMPARATOR | - |
| Cetuximab 500 mg/m^2 every 2 weeks | ACTIVE_COMPARATOR | - |
| Cetuximab 250 mg/m^2 weekly | ACTIVE_COMPARATOR | - |
| Cetuximab plus Capecitabine plus Cisplatin | EXPERIMENTAL | - |
| Capecitabine plus Cisplatin | ACTIVE_COMPARATOR | - |
| Cetuximab Plus Chemotherapy | EXPERIMENTAL | - |
| Chemotherapy alone | ACTIVE_COMPARATOR | - |
| Cetuximab Plus FOLFIRI | EXPERIMENTAL | - |
| FOLFIRI Alone | ACTIVE_COMPARATOR | - |
| Arm B - standard dose of cetuximab | OTHER | Patients with skin toxicity grade 1-4 or other significant toxicity who are not eligible for dose escalation will continue on the standard dose of cetuximab 250 mg/m2 weekly. No comparison between arms was planned. |
| Arm A - dose escalation of cetuximab | EXPERIMENTAL | Patients with skin toxicity grade 0 will follow an increasing dose schedule: on days 22 and 29 they will receive 350 mg/m2 and from day 36 onwards, 500 mg/m2 weekly. |
| 1 Arm | EXPERIMENTAL | encorafenib plus binimetinib plus cetuximab |
| Encorafenib and cetuximab | EXPERIMENTAL | Safety Lead-in (SLI) phase: 28 day cycles of encorafenib once daily (QD) 300 mg (4 x 75 mg oral capsule) and cetuximab 400 mg/m² initial dose (120-minute infusion), then 250 mg/m² (60-minute infusion) thereafter once weekly Randomized (Phase II) phase: 28 day cycles of encorafenib once daily (QD) 300 mg (4 x 75 mg oral capsule) and cetuximab 400 mg/m² initial dose (120-minute infusion), then 250 mg/m² (60-minute infusion) thereafter once weekly |
| Irinotecan and cetuximab or FOLFIRI and cetuximab | EXPERIMENTAL | Randomized (Phase II) phase: Either irinotecan and cetuximab or FOLFIRI and cetuximab in 28 day cycles. Irinotecan and cetuximab: * irinotecan 180 mg/m² (90-minute intravenous infusion or to study site standards) every 2 weeks and * cetuximab 400 mg/m² initial dose (120-minute intravenous infusion), then 250 mg/m² (60-minute infusion) thereafter once weekly OR FOLFIRI and cetuximab: * irinotecan 180 mg/m² (90-minute intravenous infusion or to study site standards) every 2 weeks * Folinic acid 400 mg/m² (120-minute infusion or to study site standards) or maximal dose tolerated in a prior regimen every 2 weeks * 5-FU 400 mg/m² initial dose bolus (not to exceed 15 minutes), then 1200 mg/m²/day × 2 days (total 2400 mg/m² over 46 to 48 hours) continuous infusion or maximal dose tolerated in a prior regimen every 2 weeks and * cetuximab 400 mg/m² initial dose (120-minute intravenous infusion), then 250 mg/m² (60-minute infusion) thereafter once weekly |
| 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) |
| Cetuximab plus cisplatin plus S-1 | EXPERIMENTAL | - |
| Cetuximab + Cisplatin/Carboplatin + Fluorouracil (5-FU) | EXPERIMENTAL | - |
| Cetuximab With Radiotherapy | EXPERIMENTAL | - |
| cisplatin and cetuximab | EXPERIMENTAL | - |
| cisplatin | ACTIVE_COMPARATOR | - |
| Cetuximab plus FOLFOX | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Cetuximab | DRUG | Participants received Cetuximab as an intravenous infusion at an initial dose of 400 milligrams per square meter (mg/m\^2) on Day 1 and a subsequent dose of 250 mg/m\^2 on Day 8 and Day 15 of each 21-day treatment cycle. |
| Cisplatin/Carboplatin | DRUG | Cisplatin or Carboplatin (at an equivalent dose in case of intolerability of cisplatin) was administered at a dose of 75 mg/m\^2 as an intravenous infusion on Day 1 of each 21-day treatment cycle. |
| 5-fluorouracil | DRUG | Participants received 5-fluorouracil (FU) at a dose of 750 mg/m\^2/day as a continuous intravenous infusion over 24 hours a day from Day 1 to Day 5 of each 21-day treatment cycle. |
| Oxaliplatin | DRUG | Oxaliplatin 85 mg/m\^2 infusion over 120 minutes on Day 1, Day 2, and then every 2 weeks until progression of disease, withdrawal of consent, or unacceptable toxicity. |
| Folinic Acid | DRUG | FA 200 mg/m\^2 infusion over 120 minutes on Day 1, Day 2, and then every 2 weeks until progression of disease, withdrawal of consent, or unacceptable toxicity. |
| 5Fluorouracil | DRUG | 5-FU as a bolus of 400 mg/m\^2/day intravenously over 2-4 minutes followed by 600 mg/m\^2/day infusion over 22 hours on Day 1, Day 2, and then every 2 weeks until progression of disease, withdrawal of consent, or unacceptable toxicity. |
| Cisplatin | DRUG | Subjects will receive 75 mg/m\^2 cisplatin as an IV infusion over 60 minutes on day 1 of each 3-week treatment cycle. |
| Cetuximab + concomitant boost radiotherapy | BIOLOGICAL | Cetuximab 400 milligram/square meter (mg/m\^2) intravenous (IV) infusion over 120 minutes for 1 week, subsequently followed by 250 mg/m\^2 IV infusion over 60 minutes, from week 2 to 7 along with concomitant boost radiotherapy: 72.0 Gray (Gy) total for 42 fractions in 6 weeks, initially * Once-daily fractions: 32.4 Gy in 18 fractions of 1.8 Gy for 3.6 weeks (5 fractions/week), followed by * Twice-daily fractions 39.6 Gy in 24 fractions for 2.4 weeks: morning dose 1.8 Gy/fraction for a total of 12 fractions 5 fractions/week; evening dose 1.5 Gy/fraction for a total of 12 fractions 5 fractions/week. Doses are separated by at least a 6-hour interval |
| Cetuximab plus Platinum-based Doublet Chemotherapy | DRUG | Single first dose of cetuximab 400 mg/m\^2 infusion will be administered intravenously over 120 minutes (min) followed by cetuximab 250 mg/m\^2 intravenous infusion over 60 min q1w with background platinum-based doublet chemotherapy up to maximum of 6 cycles, until progressive disease, unacceptable toxicity, or withdrawal of consent. Platinum based doublet chemotherapy will be administered as intravenous infusion as per study center included: vinorelbine 25 mg/m\^2 on Day 1 (D1) and Day 8 (D8)+cisplatin 80 mg/m\^2 on D1; or gemcitabine 1250 mg/m\^2 on D1 and D8+cisplatin 75 mg/m\^2 on D1; or gemcitabine 1000 mg/m\^2 on D1 and D8+carboplatin at dose to reach area under curve (AUC)5 milligram\*hour/milliliter (mg\*hr/mL) on D1; or Docetaxel 75 mg/m\^2 on D1+cisplatin 75 mg/m\^2 on D1; or paclitaxel 175 mg/m\^2 on D1+cisplatin 80 mg/m\^2 on D1; or paclitaxel 200 mg/m\^2 on D1+carboplatin at dose to reach AUC6 mg\*hr/mL on D1, of each 3-week treatment cycle for a maximum of 6 cycles. |
| Cetuximab 500 mg/m^2 | DRUG | Subjects who will be free of disease progression at the end of combination therapy, will enter in the maintenance therapy period. In the maintenance period, subjects will be receive cetuximab 500 mg/m\^2 as intravenous infusion every 2 weeks, until progressive disease (PD), unacceptable toxicity, or withdrawal of consent. |
| Cetuximab 250 mg/m^2 | DRUG | Subjects who will free of disease progression at the end of combination therapy, will enter in the maintenance therapy period. In the maintenance period, subjects will be receive cetuximab 250 mg/m\^2 as intravenous infusion weekly, until PD, unacceptable toxicity, or withdrawal of consent. |
| Capecitabine | DRUG | Capecitabine 1000 mg/m\^2 will be administered orally twice daily from evening of Day 1 to morning of Day 15 for every 3-week treatment cycle, until documented disease progression, unacceptable toxicity, or withdrawal of consent. |
| Cetuximab + Platinum (Cisplatin or Carboplatin) + 5Fluorouracil (5-FU) | DRUG | Subjects in will receive initial dose of 400 mg/m\^2 cetuximab (over 2 hours) followed by weekly doses of 250 mg/m\^2 (over 1 hour). All doses will be given by intravenous (IV) infusion. Subjects will receive either Cisplatin (100 mg/m\^2 on day 1) + 5-FU (1000 mg/m\^2 continuous IV from day 1 to day 4) every 3 weeks or Carboplatin (Area under the curve (AUC) 5 IV on day 1) + 5-FU (1000 mg/m\^2 continuous IV from day 1 to day 4) every 3 weeks |
| Platinum (Cisplatin or Carboplatin) + 5-FU | DRUG | All doses will be given by IV infusion. Subjects will receive either Cisplatin (100 mg/m\^2 on day 1) + 5-FU (1000 mg/m\^2 continuous IV from day 1 to day 4) every 3 weeks or Carboplatin (AUC 5 IV on day 1) + 5-FU (1000 mg/m\^2 continuous IV from day 1 to day 4) every 3 weeks |
| cetuximab + cisplatin + vinorelbine | DRUG | cetuximab given as an intravenous (i.v.) infusion every week (400mg/m\^2 initial dose and 250mg/m\^2 subsequent doses) until progressive disease (PD) + cisplatin 80mg/m\^2 i.v. infusion on day 1 of each 3-week cycle + vinorelbine 25mg/m\^2 i.v. infusion on days 1 and 8 of each 3-week cycle. |
| cisplatin + vinorelbine | DRUG | cisplatin 80mg/m\^2 i.v. infusion on day 1 of each 3-week cycle + vinorelbine 25mg/m\^2 i.v. infusion on days 1 and 8 of each 3-week cycle. |
| FOLFIRI (5-Fluorouracil, Folinic acid, Irinotecan) | DRUG | Bi-weekly Irinotecan infusion of 180mg/m\^2, Folinic Acid infusion of 400mg/m\^2 (racemic) or 200mg/m\^2 (L-form), 5-Fluorouracil bolus of 400mg/m\^2 followed by a 46-hour continuous infusion of 2400mg/m\^2 Number of Cycles: until progression or unacceptable toxicity develops |
| Dose escalation of cetuximab | DRUG | Dose, frequency \& treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 0 will follow an increasing dose schedule: on days 22 and 29 they will receive 350 mg/m2 and from day 36 onwards, 500 mg/m2 weekly |
| Standard first line treatment with cetuximab + Folfiri | DRUG | Dose, frequency \& treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 1-4 or other significant toxicity who are not eligible for dose escalation will continue on the standard dose of cetuximab: 250 mg/m2 weekly. |
| encorafenib | DRUG | 300 mg administered orally once daily (QD) |
| Binimetinib | DRUG | Binimetinib 45 mg administered orally twice daily (BID) |
| FOLFIRI | DRUG | Combination of: irinotecan ( also known as: Camptosar, Camptothecin-11 and CPT-11) intravenous infusion, folinic acid (also known as: 5-formyl tetrahydrofolic acid and leucovorin) intravenous infusion, and 5-FU (also known as; fluorouracil) intravenous bolus/intravenous infusion |
| 5-FU | DRUG | 400 mg/m2 (i.v. bolus) 2400 mg/m2 (i.v. 46h) |
| Irinotecan | DRUG | 180 mg/m2 |
| Avelumab | DRUG | 10mg/kg IV (day 1 q2w) |
| S-1 | DRUG | S-1, a combination of tegafur, gimeracil, and oteracil will be administered intravenously at a dose of 40 to 60 mg/m\^2 orally twice daily for first three consecutive weeks of 5-week cycle until disease progression, unacceptable toxicity, or withdrawal of consent. |
| cetuximab, cisplatin | DRUG | Subjects will receive an initial dose of cetuximab 400 milligram per square meter (mg/m\^2) followed by weekly doses of 250 mg/m\^2. All doses will be given by intravenous (IV) infusion. Subjects will receive cisplatin (75 mg/m\^2 IV on Day 1) every 3 weeks, with a maximum of 6 cycles. Administration of the Investigational Medicinal Product (IMP) will be stopped upon the first occurrence of disease progression, unacceptable toxicity or withdrawal of consent. |
| FOLFOX | DRUG | Oxaliplatin will be administered intravenously at a dose of 100 mg/m\^2 along with folinic acid administration intravenously at a dose of 400 mg/m\^2 (racemic) or 200 mg/m\^2 (L-form) and 5-fluorouracil administration intravenously at a dose of 400 mg/m\^2 bolus followed by a 46-hour continuous infusion of 2,400 mg/m\^2 given biweekly until disease progression, death, or consent withdrawal. |
Inclusion Criteria: * Histologically or cytologically confirmed diagnosis of SCCHN * Recurrent and/or metastatic SCCHN, not suitable for local-regional treatment * Presence of at least 1 measurable lesion according to RECIST Version 1.1 * Signed written informed consent before any trial-related act...
Cetuximab is used in oncology for cancers including head and neck carcinoma, colorectal cancer, and breast neoplasm. It is studied in EGFR expressing metastatic colorectal cancer and squamous cell carcinoma of the head and neck. It is also known as cetuximab plus platinum based doublet chemotherapy, cetuximab with cisplatin and vinorelbine, and cetuximab with concomitant boost radiotherapy.
Cetuximab targets EGFR, the epidermal growth factor receptor. It is a monoclonal antibody that acts as an inhibitor of EGFR. This target is relevant in cancers such as colorectal and head and neck carcinomas where EGFR expression is a factor.
Cetuximab is developed by Merck KGaA, which trades under the ticker MKGAF. The company is responsible for the clinical development of this monoclonal antibody across multiple cancer indications.
Cetuximab is in Phase 2 clinical development. It is an investigational agent and has been studied in completed trials, including Phase 2 and Phase 3 studies. The development program includes trials in colorectal, head and neck, and gastric cancers.
Cetuximab has been evaluated in completed trials such as NCT05217069 in RAS wild-type colorectal cancer, NCT02383966 in head and neck cancer, NCT01450319 in refractory colorectal cancer, and NCT01388790 in gastric cancer. These trials are completed and enrolled a total of 2444 participants.