Kanjinti (trastuzumab-anns)

Trastuzumab biosimilars, such as CT-P6, Ontruzant®, ABP 980, and PF-05280014, have shown efficacy in treating HER2-positive metastatic BCs, presenting a viable alternative to the reference product. Monoclonal biosimilars present a promising avenue in BC therapy, demonstrating efficacy, safety, and potential cost savings. The integration of biosimilars into cancer treatment strategies offers a means to improve accessibility to effective care while addressing economic considerations in healthcare.

Common reasons for trastuzumab-anns discontinuation were a switch to another biosimilar product (34.8%, n = 85) or to trastuzumab reference product (15.6%, n = 38). Trastuzumab-anns was widely used in various treatment settings for HER2+ breast cancer.

The trial randomized 780 patients twice to a total of 4 treatment groups (to receive or not receive denosumab; to receive nab-paclitaxel 125 mg/m2 weekly for 12 weeks or days 1 and 8 every 3 weeks for 4 cycles, both followed by 4 cycles of epirubicin/cyclophosphamide, 90/600 mg/m2 every 2 weeks/every 3 weeks according to the investigator´s choice). Carboplatin was given in triple-negative breast cancer (TNBC), and trastuzumab biosimilar ABP980 plus pertuzumab was given in human epidermal growth factor-2-positive (HER2+) BC... Irrespective of the treatment arm, higher pCR rates were observed in BRCA1/2 mutations carriers vs non-carriers. Both BRCA1/2 mutation carriers and non-carriers benefitted most from weekly nab-paclitaxel. No pronounced effect was observed for denosumab in either group.

Background ABP 980 is a biosimilar antibody to reference trastuzumab (RTZ). For patients treated with ABP 980 as compared to RTZ, there was no significant difference regarding efficacy (pCR-rates of 60.9% versus 62.8%, p = 0.829) or cardiac safety (LVEF decline in 6.5% versus 2.6%, p = 0.274). Conclusion Similarity of ABP 980 as compared to RTZ was confirmed in a real-world situation, including a large proportion of patients that have also received pertuzumab treatment.

All patients received 4 cycles of pembrolizumab (200 mg), trastuzumab biosimilar ABP 980 (loading dose (LD) 8 mg/kg bodyweight (BW), maintenance dose (MD) 6 mg/kg BW), and pertuzumab (LD 840 mg/kg BW, MD 420 mg/kg BW) q21d. Conclusions Biomarker analysis in the unique KEYRICHED-1 cohort revealed that early response at week 3, ERBB2 and immune related signatures as well as on-therapy sTIL levels predict pCR after a chemotherapy-free combination of immunotherapy and dual HER2 blockade in HER2-enriched EBC. These results pave the way for validation in larger de- escalation trials investigating short, chemotherapy-free regimens in selected patients with HER2+ EBC.

Background Trastuzumab (tras)-anns (KANJINTI™) is one of the first biosimilars of reference product (RP) Herceptin® approved in the European Union (EU) in May 2018, also approved in the United States in June 2019, for treatment of human epidermal growth factor receptor 2-positive (HER2+) early and metastatic breast cancer (BC) as well as metastatic gastric cancer. Conclusions Real-world experience patterns suggest tras-anns was used as initial treatment across treatment settings and disease stages. Few new users or switchers reported TEAEs of interest.

Patients were randomized to receive or not receive denosumab, 120 mg subcutaneously every 4 weeks for 6 cycles, and either nab-paclitaxel, 125 mg/m2 weekly for 12 weeks or days 1 and 8 every 3 weeks for 4 cycles (8 doses), followed by 4 cycles of epirubicin/cyclophosphamide, 90/600 mg/m2 (every 2 weeks or every 3 weeks). Carboplatin was given in triple-negative BC (TNBC), and trastuzumab biosimilar ABP980 plus pertuzumab was given in ERBB2-positive BC (ERBB2-positive substudy)...Nab-paclitaxel at a dosage of 125 mg/m2 weekly significantly increased the pCR rate compared with the days 1 and 8, every-3-weeks schedule overall and in TNBC, but generated higher toxicity. ClinicalTrials.gov Identifier: NCT02682693.

P2, N=80, Ongoing, GRUPPO ONCOLOGICO ITALIANO DI RICERCA CLINICA (GOIRC)

Stability data support storage of reconstituted solution at 2-8°C (36-46°F), up to 28 days. Reconstituted solution can be diluted in infusion bags containing 0.9% saline and stored for up to 24 h prior to intravenous administration.

These prespecified analyses confirm the tolerability of ABP 980 and demonstrate clinical similarity of ABP 980 and trastuzumab RP with respect to cardiac safety. No new cardiac safety signals were observed whether patients were receiving ABP 980 or switched from the RP to ABP 980.

Savings generated by switching 3,990 patients from Herceptin to KANJINTI amounted to R$ 421,166,642. CONCLUSIONS Treatment with KANJINTI proved to be cost-effective and savings generated from patients switching from Herceptin to KANJINTI could be reinvested to allow Brazilian private health insurers to improve patient care.

Most of those switching from subcutaneous originator trastuzumab to ABP 980 were being treated for metastatic disease (7/8 patients). These interim results report usage patterns of the trastuzumab biosimilar ABP 980 in Europe. There was uptake across a mixture of institution types and breast cancer treatment settings, including those with curative potential, and 40% of patients switched to ABP 980 from another trastuzumab product. Recruitment to this study is ongoing.

No new or unexpected safety signals emerged in the clinical evaluations, with the safety profile of ABP 980 consistent with that previously described for trastuzumab. Overall, the TOE data generated for ABP 980 support the conclusion that it is highly similar to trastuzumab RP, thus providing the scientific justification for extrapolation to all the approved indications of trastuzumab.

RESULTS : We found four papers from three equivalence randomized clinical trials and one non-inferiority trial comparing four trastuzumab biosimilars (SB3, ABP 980, CT-P6 and R-TPR-016) with the reference biological drug. CONCLUSIONS : The evidence was inconclusive regarding the statistical equivalence of efficacy between trastuzumab biosimilars and their reference. On the other hand, safety proved comparable.

Five trastuzumab biosimilars: MYL-1401O (Ogivri), CT-P6 (Herzuma), SB3 (Ontruzant), PF-05280014 (Trazimera), and ABP980 (Kanjinti), have now been approved by the US Food and Drug Administration (FDA) for use in HER2-positive breast cancers. This review provides an overview of these agents with special consideration of the development and approval process, including available clinical data results for these trastuzumab biosimilars. Adoption in the clinic will depend on the degree of comfort with the overall evidence.

P3, N=0, Withdrawn, iOMEDICO AG | Trial completion date: Sep 2026 --> Apr 2019 | Trial primary completion date: Dec 2023 --> Apr 2019

Methods GeparX, a phase II study, was planned to randomize 778 patients to NACT+/-denosumab (120mg s.c. q4w for 6 cycles), stratified by lymphocyte predominant BC (?50% vs >50% stromal tumor infiltrating lymphocytes [sTILs]), subtype (HER2-/HR+ vs triple negative (TNBC) vs HER2+), and epirubicin/cyclophosphamide (EC, q2w vs q3w)...Carboplatin was given in TNBC and ABP 980 + pertuzumab (biosimilar substudy) in HER2+ BC...Conclusions The results of the primary endpoints and selected secondary endpoints will be presented at the meeting. Funding: The trial was financially supported by Amgen and Celgene

Our results show that concordance between local and central pathology can decrease with increasing complexity of the pCR definition. Based on the results, it may be justified to include a central pathology review in neoadjuvant multicenter breast cancer trials with strict pCR definitions.

Methods GeparX, a phase II study, was planned to randomize 778 patients to NACT+/-denosumab (120mg s.c. q4w for 6 cycles), stratified by lymphocyte predominant BC (≤50% vs >50% stromal tumor infiltrating lymphocytes [sTILs]), subtype (HER2-/HR+ vs triple negative (TNBC) vs HER2+), and epirubicin/cyclophosphamide (EC, q2w vs q3w)...Carboplatin was given in TNBC and ABP 980 + pertuzumab (biosimilar substudy) in HER2+ BC...Conclusions The results of the primary endpoints and selected secondary endpoints will be presented at the meeting. Funding: The trial was financially supported by Amgen and Celgene.