Table 4.
Phase 3 trial parameters and primary endpoint results for the trastuzumab biosimilar(s) (candidates)
| Biosimilar (candidate) | Company | n patients | Patient setting | Primary endpoint | Equivalence (E)/ Non-inferiority (NI) margin | Primary endpoint results | Ref. | EU MAA/MA Status15 |
|---|---|---|---|---|---|---|---|---|
| ABP 980 | Amgen/ Allergan | 725 | Neoadjuvant+adjuvant EBC | tpCR |
E margin: −13%, +13% with 90% CI for RD°; 0.759, 1.318 with 90% CI for RR°° |
RD: 7.3% (1.2, 13.4)* 5.8% (−0.5, 12.0)** RR: 1.19 (1.033, 1.366)* 1.14 (0.993, 1.312)** |
55,56 | Approved as Kanjinti® on 16/05/201819 |
| BCD-022+ | Biocad | 126 | MBC | ORR | NI margin: −20% with 95% CI for RD in ORR | RD: −0.13% (−19.83%, 18.35%) | 57 | No application |
| CT-P6x | Celltrion | 475 | MBC | ORR | E margin: −0.15, 0.15 with 95% CI for RD° | RD: 5% (−0.14, 0.04) | 66 | Approved as Herzuma® on 08/02/201818 |
| 549 | Neoadjuvant + adjuvant EBC | tpCR |
E margin: −0.15, 0.15 with 95% CI for RD° 0.74, 1.35 with 95% CI for RR°° |
RD: −0.04 (−0.12, 0.05) RR: 0.93 (0.78, 1.11) |
67 | |||
| MYL-1401O | Mylan/ Biocon | 500 | MBC | ORR |
E margin: −15%, +15% with 95% CI for RD° 0.81, 1.24 with 90% CI for RR°° |
RD: 5.53 (−3.08, 14.04) RR: 1.09 (0.974, 1.211) |
61,62 | Approved as Ogivri® on 12/12/201820 |
| PF-05280014~ | Pfizer | 707 | MBC | ORR | E margin: 0.8, 1.25 with 95% CI for RR°° | RR: 0.940 (0.842, 1.049) | 65 | Approved as Trazimera® on 26/07/201817 |
| 226 | Neoadjuvant EBC | % pts with cycle 5 Ctrough >20 μg/mL | NI margin: −12.5% with 95% CI for stratified difference in Ctrough | 92.1% for PF-05280014 vs 93.3% for RP-EU (−8.02%, 6.49%) | 64 | |||
| SB3 | Samsung Bioepis | 800 | Neoadjuvant + adjuvant EBC | bpCR |
E margin: −13%, +13% with 95% CI for RD°; 0.785, 1.546 with 95% CI for RR°° |
RD: 10,70% (4.13, 17.26) RR: 1.259 (1.085, 1.460) |
54,63 | Approved as Ontruzant® on 15/11/201716 |
bpCR breast pathological complete response; CI confidence interval; E equivalence; EBC early breast cancer; MA marketing authorisation; MAA marketing authorisation application; MBC metastatic breast cancer; n number; NI non-inferiority; NR not reported; ORR overall response rate; RD risk difference; RP reference product; RR risk ratio; tpCR total pathological complete response (breast + lymph nodes)
Data are derived from published scientific literature (full text or abstract)
*Based on local review
**Based on central independent review
°EMA advised
°°FDA advised
+BCD-022 is authorised in Russia, but has not been submitted to FDA or EMA and most likely would not be considered as a biosimilar following stringent FDA or EMA requirements
xThe phase 3 data in MBC for CT-P6 were not submitted to EMA as part of the marketing authorisation application and were thus not evaluated when assessing the totality of evidence for biosimilarity50
~The pivotal phase 3 trial for PF-05280014 was conducted in the MBC setting. Supportive efficacy data have been gathered in a phase 3 clinical trial in patients with early breast cancer in the neoadjuvant setting (PK endpoint as primary endpoint52)