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Breast Neoplasms

Breast Diseases

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Trastuzumab

Immune Checkpoint Inhibitors

Pembrolizumab

Pertuzumab

Antineoplastic Agents, Immunological

Trial treatment is defined as neoadjuvant therapy only. The Investigational Medicinal Products (IMPs) are pembrolizumab, trastuzumab biosimilar and pertuzumab.

* Trastuzumab Biosimilar (Trazimera®) - Investigational Medicinal Product

  * Loading dose: 8 mg/kg bodyweight at initial administration infusion over 90 min; monitor patient for at least 6 h afterwards.
  * Maintenance dose: 6 mg/kg bodyweight, over 30-90 min; monitor patient for 2 h afterwards.
  * Route: Intravenous infusion.
  * Schedule: Every 3 weeks during the neoadjuvant phase.
* Pertuzumab (Perjeta®) - Investigational Medicinal Product

  * Loading dose: 840 mg, initial administration.
  * Maintenance dose: 420 mg.
  * Route: Intravenous infusion.
  * Schedule: Every 3 weeks during the neoadjuvant phase.
* Pembrolizumab (Keytruda®) - Investigational Medicinal Product

  * Dose: 200 mg.
  * Route: Intravenous infusion.
  * Schedule: Every 3 weeks during the neoadjuvant phase.

Intravenous infusion; 200 mg; every 3 weeks

Intravenous infusion; 8 mg/kg loading dose, thereafter 6 mg/kg; every 3 weeks

Trastuzumab Biosimilar ABP 980

Intravenous infusion; 840 mg/kg loading dose, thereafter 420 mg/kg; every 3 weeks

s.kuemmel@kem-med.com Kuemmel, Professor

Keyriched-1 is a multicenter, interventional, prospective, single arm, open label, neoadjuvant phase II trial evaluating the pathological complete response (pCR) rate induced by pembrolizumab in combination with the dual anti-HER2 blockade consisting of trastuzumab biosimilar ABP 980 and pertuzumab in early breast cancer patients with molecular HER2-enriched intrinsic subtype tested by PAM50.

HER2-positive breast cancer is best defined by multiparameter gene expression profiling rather than analysis of the overexpression/amplification status of only HER2. As this subgroup is often correlated with a high expression of TILs and PD/PD-L1, immunogenic therapy strategies seem very promising. The pCR highly correlates with the overall outcome of patients with HER2-positive breast cancer \[7\]. Therefore, the pCR rate after neoadjuvant treatment has been adopted as a surrogate endpoint and, more recently, as a basis for accelerated drug approval \[38\].

Due to the high number of patients achieving a pCR after standard treatment of anti-HER2 therapy combined with chemotherapy, de-escalated strategies seem promising and designing a chemotherapy-free trial regimen is therefore modern, justifiable and of high scientific value. Therefore, we designed a prospective phase II, single arm, hypothesis-generating trial investigating the rate of pCR in patients with HER2-enriched breast cancer receiving four cycles of dual anti-HER2 blockade in combination with the checkpoint inhibitor pembrolizumab. Further translational research will be added to gain further insight into the tumor response or resistance to this treatment approach. The addition of standard chemotherapy after this study treatment will be at the discretion of the investigator. In case of a non-pCR after study treatment, continuing treatment with chemotherapy and antihormonal therapy in case of HR positive disease is highly recommended.

A multicenter, interventional, prospective, single arm, open label, neoadjuvant phase II trial evaluating the pathological complete response (pCR) rate induced by pembrolizumab in combination with the dual anti-HER2 blockade consisting of trastuzumab biosimilar and pertuzumab in early breast cancer patients with molecular HER2-enriched intrinsic subtype tested by PAM50.

A Study With Pembrolizumab in Combination With Dual Anti-HER2 Blockade With Trastuzumab and Pertuzumab in Early Breast Cancer Patients With Molecular HER2-enriched Intrinsic Subtype (Keyriched-1)

A Prospective, Multicenter, Open Label, Neoadjuvant Phase II Single Arm Study With Pembrolizumab in Combination With Dual Anti-HER2 Blockade With Trastuzumab and Pertuzumab in Early Breast Cancer Patients With Molecular HER2-enriched Intrinsic Subtype

pCR defined as no invasive tumor in breast and lymph nodes (ypT0/is, ypN0) at surgery after study treatment

AEs classified by System Organ Class (SOC) and Preferred Terms (PT), descriptive analysis by number of observations and their percentage.

Descriptive analysis by number of observations and their percentage.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Study With Pembrolizumab in Combination With Dual Anti-HER2 Blockade With Trastuzumab and Pertuzumab in Early Breast Cancer Patients With Molecular HER2-enriched Intrinsic Subtype (Keyriched-1)	NCT03988036	Breast Cancer	Pembrolizumab Trastuzumab Bio... Pertuzumab	18 Years -	West German Study Group
A Study With Pembrolizumab in Combination With Dual Anti-HER2 Blockade With Trastuzumab and Pertuzumab in Early Breast Cancer Patients With Molecular HER2-enriched Intrinsic Subtype (Keyriched-1)	NCT03988036	Breast Cancer	Pembrolizumab Trastuzumab Bio... Pertuzumab	18 Years -	West German Study Group

Spots Global Cancer Trial Database for trastuzumab biosimilar abp 980