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)

  • STATUS
    Recruiting
  • End date
    Dec 26, 2021
  • participants needed
    46
  • sponsor
    West German Study Group
Updated on 26 January 2021
estrogen
x-rays
progesterone
pertuzumab
HER2
primary tumor
trastuzumab
progesterone receptor
erbb2
breast cancer staging
mammogram
magnetic resonance imaging of breast

Summary

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.

Description

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.

Details
Condition Breast Cancer, Breast Cancer Diagnosis, breast carcinoma, cancer, breast
Treatment Pembrolizumab, Pertuzumab, Trastuzumab Biosimilar ABP 980
Clinical Study IdentifierNCT03988036
SponsorWest German Study Group
Last Modified on26 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Female participants, who are at least 18 years of age on the day of signing informed consent with newly histologically locally confirmed diagnosis of HER2neu 2+ or 3+ breast cancer
Have previously untreated, non-metastatic (M0) HER2-enriched breast cancer defined as the following combined primary tumor (T) and regional lymph node (N) staging per American Joint Committee on Cancer (AJCC) for breast cancer staging criteria version 7 as assessed by the Investigator based on radiological and/or clinical assessment
T1c, N0-N2; T2, N0-N2; T3, N0-N2
Patients with HER2-enriched, estrogen and/ or progesterone receptor positive or negative breast cancer defined by American Society of Clinical Oncology (ASCO) / College of American Pathologists (CAP) guidelines can be included
Availability of tumor imaging performed within three months prior to start of screening phase: breast ultrasound and computed tomography (CT) thorax/abdomen or chest X-ray/liver ultrasound, bone scan, mammography or breast magnetic resonance imaging (MRI) (according to local standard)
Ability to provide archived tumor tissue sample or at least two newly obtained separate tumor cores from the primary tumor or excisional biopsy of a tumor lesion not previously irradiated at screening to the central laboratory. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred over slides. Newly obtained biopsies are preferred over archived tissue
Note: If submitting unstained cut slides, newly cut slides should be submitted
to the testing laboratory within 14 days from the date slides are cut
Patients are eligible to be included in the trial only if all of the following
criteria apply [items 1-6 must be met by the patient to be enrolled into the
trial and before the start of the screening phase]
Female patients, who are at least 18 years of age on the day of signing informed consent, with newly histologically locally confirmed diagnosis of HER2neu 2+ or 3+ breast cancer
Previously untreated, non-metastatic (M0) HER2-enriched breast cancer defined as the following combined primary tumor (T) and regional lymph node (N) staging per AJCC for breast cancer staging criteria version 7 as assessed by the investigator based on radiological and/or clinical assessment
T1c, N0-N2
T2, N0-N2
T3, N0-N2
Patients with HER2-enriched, estrogen and/or progesterone receptor-positive or -negative breast cancer defined by ASCO/CAP guidelines
Availability of tumor imaging performed within three months prior to start of screening phase: breast ultrasound and CT thorax/abdomen or chest X-ray/liver ultrasound, bone scan, mammography or breast MRI (according to local standard)
Ability to provide an archived tumor tissue sample or at least two newly obtained separate tumor cores from the primary tumor or excisional biopsy of a tumor lesion not previously irradiated at screening to the central laboratory. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred over slides. Newly obtained biopsies are preferred over archived tissue
Note: If submitting unstained cut slides, newly cut slides should be submitted
to the testing laboratory within 14 days from the date slides are cut
\. A female patient is eligible to participate if she is not pregnant, not
breastfeeding, and if at least one of the following conditions applies
not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
a WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 7 months after the last dose of study treatment Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the patient
The patient provides written informed consent for participation in the trial. The patient may also provide consent for future biomedical research. However, the patient may participate in the main trial without participating in future biomedical research
Confirmed HER2neu (IHC 2+ status and amplification [e.g. by FISH] or IHC 3+ status) tumor identification by local pathology
Confirmed HER2-enriched status by PAM50 testing
Confirmed HR+ or HR- status
Female patients of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or borderline, a serum pregnancy test will be required
Note: In the event that 72 hours have elapsed between the screening pregnancy
test and the first dose of study treatment, another pregnancy test (urine or
serum) must be performed and must be negative in order for the patient to
start receiving study medication
\. Left ventricular ejection fraction (LVEF) of 55% or institution lower
limit of normal (LLN) as assessed by echocardiogram (ECHO) or multigated
acquisition (MUGA) scan performed at screening or performed in clinical
routine within 6 weeks prior to first treatment allocation
\. Normal ECG performed at screening or performed in clinical routine within
weeks prior to first treatment allocation
\. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
Evaluation of ECOG performance status is to be performed within 10 days prior
to the date of treatment initiation
\. Adequate organ function as defined in the following table. Specimens must
be collected within 10 days prior to the start of study treatment

Exclusion Criteria

Patients are excluded from the trial if any of the following criteria apply
Patient has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T cell receptor (e.g. CTLA-4, OX 40, CD137) or has participated in MK-3475 clinical trials
Patient has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to first dose of study medication
Note: Patients must have recovered from all AEs due to previous therapies to
Grade 1 or baseline. Patients with Grade 2 neuropathy may be eligible
Note: If the patient received major surgery, they must have recovered
adequately from the toxicity and/or complications from the intervention prior
to starting study treatment
\. Patient has received a live vaccine within 30 days prior to the first dose
of study drug. Examples of live vaccines include, but are not limited to, the
following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow
fever, rabies, Bacillus Calmette-Gurin (BCG), and typhoid vaccine. Seasonal
influenza vaccines for injection are generally killed virus vaccines and are
allowed; however, intranasal influenza vaccines (e.g. FluMist) are live
attenuated vaccines and are not allowed
\. Patient is currently participating in or has participated in a trial of an
investigational agent or has used an investigational device within 4 weeks
prior to the first dose of study treatment
Note: Patients who have entered the follow-up phase of an investigational
trial may participate as long as it has been 4 weeks after the last dose of
the previous investigational agent. Patient should be excluded if she received
an investigational agent with anti-cancer or anti-proliferative intent within
the last 12 months
\. Patient has a diagnosis of immunodeficiency or is receiving chronic
systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone
equivalent) or any other form of immunosuppressive therapy within 7 days prior
to the first dose of study drug
\. Prior malignancy with a disease-free survival of 5 years before signing
informed consent
Note: Patients with basal cell carcinoma of the skin, squamous cell carcinoma
of the skin, or carcinoma in situ (e.g. ductal carcinoma in situ, cervical
cancer in situ) that have undergone potentially curative therapy are not
excluded
\. Patient has a known hypersensitivity to the components of the study
therapy, its analogs, murine proteins or any of the excipients
\. Patient has active autoimmune disease that has required systemic treatment
in the past 2 years (i.e. with use of disease-modifying agents
corticosteroids or immunosuppressive drugs). Replacement therapy (e.g
thyroxine, insulin, or physiologic corticosteroid replacement therapy for
adrenal or pituitary insufficiency, etc.) is not considered a form of systemic
treatment
\. Patient has a significant cardiovascular disease, such as
LVEF <55%
History of myocardial infarction, acute coronary syndrome or coronary angioplasty/stenting/bypass grafting within the past 6 months
Congestive heart failure (CHF) New York Heart Association (NYHA) Class I-IV or history of CHF NYHA class III or IV 10. Severe and relevant co-morbidity that would interact with the application of cytotoxic agents or the participation in the trial, including but not confined to
Unstable arrhythmias requiring treatment, i.e., atrial tachycardia with a heart rate 100/min at rest, significant ventricular arrhythmia (ventricular tachycardia) or higher-grade AV-block
Angina pectoris within the last 6 months requiring anti-anginal medication
Clinically significant valvular heart disease
Evidence of myocardial infarction on electrocardiogram (ECG)
Poorly controlled hypertension (e.g. systolic >180 mm Hg or diastolic >100 mm Hg). 11. Inadequate organ function including but not confined to
hepatic impairment (Child Pugh Class C)
pulmonary disease (severe dyspnea at rest due to complications of advanced malignancy or requiring oxygen therapy). 12. Patient has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis. 13. Patient has an active infection requiring systemic therapy. 14. Patient has a known history of human immunodeficiency virus (HIV), hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (defined as detectable HCV RNA [qualitative] is detected)
Note: Testing of hepatitis B is required in all patients during screening as
standard of care according to current guidelines in early breast cancer
HIV and hepatitis C testing is required in all patients with significant risk
factors (see checklist below). There is a significant risk if one of the items
on the checklist applies for the patient
HIV and hepatitis C risk checklist
Patient has frequently changing sexual partners
Patient practices anal sex
The patient has already been diagnosed with another sexually transmitted infection, such as syphilis or gonorrhea
Patient suffers from drug abuse
Tattoos or piercings abroad within the last 4 months
Presence of a positive HIV and/or Hepatitis C test
Patient received a blood transfusion before 1992
Patient is an organ transplant recipient
The patient's mother has/had HIV and/or hepatitis C
Patient has elevated liver blood values (relevant for hepatitis C risk). 15. Patient has a known history of active TB (Bacillus Tuberculosis). 16. Patient has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator. 17. Patient has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 18. Patient is pregnant or breastfeeding, or expecting to conceive children or planning to breastfeed within the projected duration of the trial, starting with the screening visit through 7 months after end of treatment. 19. Male patients with breast cancer. 20. History of breast cancer. 21. Factors indicating risk of poor compliance. 22. Pathological laboratory assessments
Thrombocytopenia > CTCAE grade 1
Increases in ALT/AST > CTCAE grade 1
Hypokalemia > CTCAE grade 1
Neutropenia > CTCAE grade 1
Anemia > CTCAE grade 1 23. Non-operable breast cancer including inflammatory breast cancer
Clear my responses

How to participate?

Step 1 Connect with a site
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar
Name

Primary Contact

site
Name

0/250
Preferred Language
Other Language
Please verify that you are not a bot.

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note