Results From 5 Biosimilar Trastuzumab Studies

Poster presentations at this week’s European Society for Medical Oncology (ESMO) conference include the results of 5 studies on biosimilar trastuzumab candidates.

Biosimilar Candidate

Study

Results

Conclusions

ABP 980

Amgen

Clinical study of primary efficacy analysis. Compared ABP 980 with RTZ on pCR in women with HER2+ EBC.

Primary endpoints: RD and RR of pCR in breast tissue and axillary lymph nodes of tumor samples.

Secondary endpoint: safety.

pCR evaluable population was 696 patients (ABP 980, n = 358; RTZ, n = 338).

48.0% and 40.5% of patients in ABP 980 arm and RTZ arm, respectively, achieved pCR.

RD and RR of pCR were 7.3% and 1.19%.

Study shows clinical equivalence of ABP 980 and RTZ in the neoadjuvant setting and adds to the totality of evidence demonstrating similarity between ABP 980 and RTZ.

CT-P6

Celltrion

Phase 3 study comparing efficacy and safety of RTZ and biosimilar candidate CT-P6 in women with HER2+ EBC.

549 patients with HER2+ EBC were randomized to receive CT-P6 (n = 271) or RTZ (n = 278) with docetaxel (cycles 1 to 4) and 5-FU, epirubicin, and CP (cycles 5 to 8). After surgery, patients received CT-P6 or RTZ monotherapy up to 10 cycles.

Primary endpoint: pCR rate at surgery.

Secondary endpoints: ORR, PK, PD, and safety.

pCR rate was 46.8% in CT-P6 and 50.4% in RTZ.

The 95% CIs for estimate of treatment difference were within equivalence margin in both PPS and ITT.

The study demonstrated the equivalence of efficacy between CT-P6 and RTZ in EBC.

Secondary efficacy endpoints also supported similarity of 2 study drugs. CT-P6 was well tolerated with a similar safety profile to RTZ.

SB3

Samsung Bioepsis

1-year results on safety, immunogenicity, EFS, and OS in trial of RTZ versus biosimilar candidate SB3 in HER2+ EBC study, comparing neoadjuvant SB3 or RTZ for 8 cycles concurrently with chemotherapy.

After surgery, pts underwent 10 cycles of adjuvant SB3 or RTZ as randomized.

Primary endpoint bpCR rate; secondary endpoints included safety, immunogenicity, EFS, and OS.

765 pts completed adjuvant therapy (SB3, n = 381; RTZ, n = 384). TEAE incidence was comparable between arms.

EFS rates: 92.2% in SB3 and 91.6% in RTZ. There were 6 deaths (SB3, n = 1; RTZ, n = 5).

Immunogenicity was low and comparable, with ADAs detected in 3 pts per arm.

1-year safety, immunogenicity, and survival results further support biosimilarity established between SB3 and RTZ.

PF-05280014

Pfizer

Comparative clinical trial evaluating efficacy, safety, immunogenicity, and PK of biosimilar candidate PF-05280014 versus RTZ sourced from the EU, both given with docetaxel and carboplatin chemotherapy for operable HER2+ EBC.

Pts (n = 226) were stratified by primary tumor size and hormone receptor status; randomized 1:1 to receive PF-05280014 or trastuzumab-EU with chemotherapy for 6 treatment cycles.

Study powered to test whether PF-05280014 was noninferior to trastuzumab-EU in % of pts with pre-dose cycle 6 >20 µg/mL.

Efficacy measured by % of pts with pCR and ORR. Safety and immunogenicity also assessed.

% of pts with pre-dose cycle 6 >20 µg/mL was 92.1% for PF-05280014 and 93.3% for RTZ-EU, above the non-inferiority margin.

pCR rate was 47.0% for PF-05280014, 50.0% for RTZ-EU.

ORR was 88.1% for PF-05280014 and 82.0% for RTZ-EU; TEAEs reported by 38.1% versus 45.5% of pts, respectively.

No pts in PF-05280014 and 1 in RTZ-EU group had positive ADA titer.

PF-05280014 demonstrated similarity in efficacy, safety, and immunogenicity, and noninferiority in PK, to RTZ-EU.

PF-05280014

Pfizer

Randomized, double-blind efficacy and safety study of biosimilar candidate PF-05280014 versus RTZ sourced from the EU, with paclitaxel, as first-line treatment for pts with HER2+ MBC.

Pts (n = 707) were randomized 1:1 to PF-05280014 or RTZ-EU, both given with paclitaxel.

Trastuzumab was given weekly until at least week 33, with treatment continuing until progression.

Primary endpoint was ORR by week 25 or week 33.

Secondary endpoints included safety, measures of tumor control, immunogenicity, and PK.

The RR for ORR was 0.940 for PF-05280014 over RTZ-EU, with a 95% CI of 0.842-1.049, within pre-specified equivalence margin.

1-yr progression-free survival and 1-yr survival were similar between groups. Safety profile, including SAEs, was similar in both arms; no new safety signals identified. After study drug initiation, all pts tested negative for ADAs, except 1 pt receiving RTZ-EU. Mean trough and peak serum concentrations similar for both agents up to cycle 5 day 8. Study ongoing in 558 pts.

In pts receiving first-line treatment for HER2+ MBC, PF-05280014 was similar to RTZ-EU in terms of efficacy, safety, immunogenicity, and PK.

ADA indicates antidrug antibody; bPCR, breast pathologic complete response; CI, confidence interval; CP, cyclophosphamide; EFS, event-free survival; EU, European Union; 5-FU, 5-fluorouracil; HER2+ EBC, HER2-positive early breast cancer; ITT, intention to treat; MBR, metastatic breast cancer; ORR, overall response rate; OS, overall survival; pCR, pathologic complete response; PD, pharmacodynamics; PK, pharmacokinetics; PPS, palliative prognostic score; pts, patients; RD, risk difference; RR, risk ratio; RTZ, reference trastuzumab; SAE, serious adverse event; TEAE, treatment-emergent adverse event; yr, year.