MATCH Treatment Subprotocol J: Trastuzumab and Pertuzumab (HP) in Patients With Non-Breast, Non-Gastric/GEJ, and Non-Colorectal Cancers With HER2 Amplification
Phase: PHASE2
Conditions: Malignant Solid Neoplasm
Sponsor: National Cancer Institute (NCI)

i 
28 State Street, Suite 1100, Boston, MA 02109
p: 857.504.2900 
f: 617. 589.0914
ecog-acrin.org
November 10, 2022
, MS RAC
Quality Assurance Section
CTEP, DCT, NCI
6130 Executive Blvd, EPN Room 
Bethesda, MD 20892
Dear 
:
Enclosed is Addendum #31 to EAY131-J, MATCH Treatment Subprotocol J: Trastuzumab and 
Pertuzumab (HP) in Patients with Non-Breast, Non-Gastric/GEJ, and Non-Colorectal Cancers 
with HER2 Amplification.
Please replace your current copy of the protocol and Informed Consent document with these 
updated versions. We recommend that each institution maintain a file containing the original 
protocol, Informed Consent, and all subsequent revisions/versions.
IRB Review Requirements:
This addendum has been reviewed and approved by the Central IRB, which is the sole 
IRB of record for this study. Local IRB review and approval is unnecessary.
Implementation of this addendum must occur on the activation date. Sites are not 
permitted to conduct the study utilizing outdated versions of any MATCH protocol documents 
after the activation date of this addendum.
This addendum is in response to the Trastuzumab Rapid Request for Amendment (RRA) from 
Dr.
 dated February 2, 2022.
Re: Review of Amendment #44 of Protocol #EAY131-J: “MATCH Treatment Subprotocol J: 
Trastuzumab and Pertuzumab (HP) in Patients with Non-Breast, Non-Gastric/GEJ, and 
Non-Colorectal Cancers with HER2 Amplification.” The following are ECOG-ACRIN’s 
responses to the CTEP review comments dated 9/28/22. Please note that the Principal 
Investigator’s comments appear in bold below.
I.
Comments Requiring a Response – Administrative & Editorial Issues: 
# 
Section
Comments
1.
ICD - Possible Side 
Effects of 
Trastuzumab
Possible Side Effects of Trastuzumab: The risk list table definition for 
OCCASIONAL, SOME MAY BE SERIOUS events was updated 
inappropriately. 
Change to: In 100 people receiving Trastuzumab (herceptin) and 
Herceptin HylectaTM (SQ trastuzumab), from 4 to 20 may have:
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ii 
# 
Section 
Comments 
PI Response: This change has been made. 
2. 
ICD - Possible Side 
Effects of 
Trastuzumab 
Possible Side Effects of Trastuzumab: The risk list table definition for 
RARE, AND SERIOUS events was updated inappropriately.  
Change to: In 100 people receiving Trastuzumab (herceptin) and 
Herceptin HylectaTM (SQ trastuzumab), 3 or fewer may have: 
PI Response: This change has been made. 
The following revisions to the EAY131-J protocol have been made in this addendum: 
 
Section 
Change 
1. 
Cover Page 
Updated Version Date and addendum number. 
2. 
3.3 
Updated CAEPR for Trastuzumab (Herceptin) to Version 2.6, December 
14, 2021. 
The following revisions to the EAY131-J Informed Consent Document have been made in this 
addendum: 
 
Section 
Change 
1. 
Cover Page 
Updated Version Date. 
2. 
Possible Side 
Effects of 
Trastuzumab 
Updated Risk List for Trastuzumab (Herceptin) to Version Date: December 
14, 2021. 
If you have any questions regarding this addendum, please contact 
 or 
. 
We request review and approval of this addendum to EAY131-J so ECOG-ACRIN may activate 
it promptly.   
Thank you.  
Sincerely, 
 
 
 
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EAY131-J 
1 
Molecular Analysis for Therapy Choice (MATCH)
MATCH Treatment Subprotocol J: Trastuzumab and 
Pertuzumab (HP) in Patients with Non-Breast, Non-
Gastric/GEJ, and Non-Colorectal Cancers with HER2 
Amplification 
TRASTUZUMAB AND PERTUZUMAB TREATMENT 
SUBPROTOCOL CHAIR:
, MB, BCh
TRASTUZUMAB AND PERTUZUMAB SUBPROTOCOL 
TRANSLATIONAL CHAIR:
, MD, PhD
Version Date: November 10, 2022
NOTE: This subprotocol (EAY131-J) should 
be used in conjunction with the 
MATCH Master Protocol (EAY131).
SUBPROTOCOL ACTIVATION DATE
March 13, 2017 (Incorporated In Addendum #7)
Addendum #10 – 5/17
NOTE: As of 11/17, all protocol changes will 
be noted by addendum number.
Addendum #13
Addendum #18
Addendum #21
Addendum #22
Addendum #25
Addendum #31
Agent
IND#
NSC#
Supply
Trastuzumab
IND Sponsor: DCTD, NCI IND#: 
688097
NCI Supplied
Pertuzumab
IND Sponsor: DCTD, NCI IND#: 
740102
NCI Supplied
Rev. Add13
Rev. Add25
Rev. Add25
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ECOG-ACRIN 
EAY131-J 
Cancer Research Group 
Version Date: November 10, 2022 
2 
Table of Contents 
Schema ...................................................................................................................... 4 
1. Introduction ........................................................................................................ 5 
1.1 Trastuzumab ............................................................................................. 6 
1.2 Pertuzumab ............................................................................................... 8 
1.3 Dual anti-HER2 Therapy ............................................................................ 9 
1.4 Summary ................................................................................................. 10 
2. Selection of Patients ......................................................................................... 12 
2.1 Registration to Treatment ....................................................................... 12 
3. Trastuzumab and Pertuzumab (HP) Treatment Plan ........................................ 14 
3.1 Administration Schedule ......................................................................... 14 
3.2 Adverse Event Reporting Requirements ................................................. 14 
3.3 Comprehensive Adverse Events and Potential Risks list (CAEPR) for 
Trastuzumab (Herceptin, NSC 688097) ................................................... 17 
3.4 Comprehensive Adverse Events and Potential Risks list (CAEPR) for 
Pertuzumab (NSC 740102) ...................................................................... 21 
3.5 Dose Modifications ................................................................................. 25 
3.6 Supportive Care ....................................................................................... 30 
3.7 Duration of Agent-specific treatment ..................................................... 31 
3.8 Duration of Follow-Up ............................................................................. 31 
4. Study Parameters .............................................................................................. 32 
4.1 Therapeutic Parameters for Trastuzumab and Pertuzumab Treatment 32 
5. Drug Formulation and Procurement ................................................................. 34 
5.1 Trastuzumab (NSC #688097) ................................................................... 35 
5.2 Pertuzumab (NSC #740102) .................................................................... 38 
6. Translational Studies ......................................................................................... 40 
7. References ........................................................................................................ 40 
Appendix I  Actionable Mutations for Sub-Protocol EAY131-J ................................ 43 
Appendix II  Patient Drug Information Handout and Wallet Card .......................... 44 
 
 
 
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ECOG-ACRIN 
EAY131-J 
Cancer Research Group 
Version Date: November 10, 2022 
3 
TREATMENT SUBPROTOCOL CHAIR 
, M.B., B.Ch., M.D. 
UCC College of Medicine and Health, 
University College Cork 
Western Gateway Building, 4.110 
Western Road 
Cork, Ireland 
Phone: 
Email: 
  
 
TRANSLATIONAL CHAIR 
, M.D., Ph.D. 
University of Washington Medical Center 
825 Eastlake Avenue East  
G-4830  
Seattle, WA 98109 
Phone:
Email: 
 
 
 
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ECOG-ACRIN 
EAY131-J 
Cancer Research Group 
Version Date: November 10, 2022 
4 
Schema 
Long-Term Follow-Up
Trastuzumab and Pertuzumab (HP) 
IV every 3 weeks (Trastuzumab: 8 
mg/kg loading dose, then 6 mg/kg; 
Pertuzumab: 840 mg as a loading 
dose, then 420 mg)
Until progression or unacceptable 
toxicity
Cycle = 21  days
Accrual Goal: 35
 
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ECOG-ACRIN 
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Version Date: November 10, 2022 
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1. 
Introduction 
Amplification and/or overexpression of the human epidermal growth factor receptor 2 
(HER2) gene is present in approximately 15-20% of breast cancers and has been 
associated with an aggressive breast cancer phenotype and a poor prognosis.(1) HER2 
is a member of the epidermal growth factor receptor (EGFR or ErbB) family of receptor 
tyrosine kinases and is a key target for HER2-targeted therapy.(2) The humanized 
monoclonal antibody trastuzumab (Herceptin) was approved by the Food and Drug 
Administration (FDA) for use in the metastatic setting in the late 1990s based on 
improved clinical benefit and overall survival (OS). In 2005, trastuzumab was also 
approved in the adjuvant setting for patients with HER2-positive early breast cancer 
when combined with chemotherapy(3). Trastuzumab is also approved for the treatment 
of patients with HER2-overexpressing metastatic gastric/GEJ adenocarcinoma based on 
an observed survival advantage when combined with standard chemotherapy versus 
chemotherapy alone.(4)  
Despite the advances noted above, resistance to trastuzumab is a common clinical 
dilemma. Dysregulation of downstream signalling pathways, alternative receptor tyrosine 
kinase signaling and accumulation of the truncated kinase active p95-HER2 have all 
been implicated in resistance to trastuzumab(5). Based on extensive preclinical and 
clinical development, additional HER2-targeted therapies are now available for patients 
with HER2-positive breast cancer and include the HER2/HER3 dimerization inhibitor 
pertuzumab (Perjeta). Pertuzumab is approved for treatment of patients with HER2-
positive metastatic breast cancer, and recently received accelerated approval for use in 
the neoadjuvant setting in combination with trastuzumab and chemotherapy. Based on 
the information provided below, it appears that the combination of trastuzumab and 
pertuzumab is more effective than either agent alone, in a variety of settings in breast 
cancer. 
A variety of tumor types other than breast and gastric/GEJ adenocarcinoma demonstrate 
amplification of the HER2 receptor (Figure 1), which may indicate a heavier dependence 
of these tumors on this pathway than in those tumors without amplification.(6,7) These 
patients are unlikely to have had prior trastuzumab. Thus, the combination of 
trastuzumab and pertuzumab may result in higher response rate and/or prolonged 
progression-free survival for this group of patients and is being investigated in this arm of 
the NCI MATCH trial.  
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ECOG-ACRIN 
EAY131-J 
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Version Date: November 10, 2022 
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Figure 1: ERBB2 Alteration Frequency in Solid Tumors (www.cBioPortal.org) 
1.1 
Trastuzumab 
Trastuzumab binds to extracellular domain IV of the HER2 receptor, inhibits 
downstream signaling and stimulates antibody-dependent cell-mediated 
cytotoxicity (ADCC)(8). It is becoming increasingly recognized that trastuzumab 
may also harness the immune system against HER2(9). 
1.1.1 
Preclinical Studies 
Trastuzumab has been shown, in both in vitro assays and in animals, 
to inhibit the proliferation of human tumor cells that overexpress 
HER2. In vitro, trastuzumab mediated antibody-dependent cell-
mediated cytotoxicity (ADCC) is preferentially exerted on HER2-
overexpressing cancer cells compared with cancer cells that do not 
overexpress HER2.(10) Preclinical in vivo studies revealed no direct 
toxicity of trastuzumab via the intravenous, subcutaneous or 
intrathecal route. Reproductive toxicity studies in female monkeys did 
not reveal any impaired fertility, embryotoxicity, or effects on fetal 
development. An increased risk of cardiac dysfunction observed in 
clinical trials, particularly in combination with anthracycline therapy, 
was not predicted by preclinical safety studies. (Trastuzumab 
Investigator Brochure) 
1.1.2 
Clinical Studies 
1.1.2.1 
Breast Cancer 
Single agent trastuzumab has been investigated as 
second- or third-line therapy for women with HER2-
overexpressing metastatic breast cancer. Its use resulted 
in an objective response rate (ORR) of 15% and a median 
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ECOG-ACRIN 
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survival of 13 months. (11) When used as monotherapy in 
the first-line setting, the ORR was 26%.(12) The use of 
trastuzumab in combination with chemotherapy as first-line 
treatment of women with metastatic breast cancer 
significantly prolonged median time to disease progression 
(TTP) and overall survival (OS), when compared with 
chemotherapy alone.(13) 
Specifically, the combination of trastuzumab and docetaxel 
significantly increased ORR (61% versus 34%) and 
prolonged the median time to disease progression (by 5.6 
months), compared with patients treated with docetaxel 
alone. Median survival was also significantly increased in 
patients receiving the combination, compared with those 
receiving docetaxel alone (31.2 months versus 22.7 
months).(14) A number of clinical trials have indicated that 
the addition of 1 year of trastuzumab to adjuvant 
chemotherapy regimens in HER-2 positive breast cancer 
patients results in an approximately 50% reduction in 
breast cancer recurrence and 35% reduction in 
mortality.(15-17) 
1.1.2.2 
Gastric/GEJ adenocarcinoma 
ToGA (Trastuzumab for Gastric Cancer) was an open-
label, randomized, multicenter, Phase III study, which 
evaluated the efficacy of trastuzumab in combination with a 
fluoropyrimidine and cisplatin versus chemotherapy alone, 
as first-line therapy in patients with locally advanced or 
metastatic HER2-positive adenocarcinoma of the stomach 
including the gastroesophageal junction (GEJ).(4) Median 
overall survival was 13.8 months (95% CI 12-16) in those 
assigned to trastuzumab plus chemotherapy compared 
with 11.1 months (95% CI 10-13) in those assigned to 
chemotherapy alone (hazard ratio 0.74; 95% CI 0.60-0.91; 
p=0.0046).An exploratory post-hoc analysis found that the 
median OS in patients with high HER2-expressing tumors 
(IHC 2+/FISH+ and IHC3+) was extended from 11.8 
months to 16 months (HR 0.65; 95% CI [0.51-0.83]). This 
study led to FDA approval of trastuzumab for this 
indication.  
1.1.2.3 
Other tumor types 
A multicenter phase II single arm NCI trial included 
patients with advanced urothelial carcinoma selected 
based on HER2 overexpression by immunohistochemistry 
(IHC), gene amplification and/or elevated serum HER2, no 
prior chemotherapy for metastasis and adequate organ 
function.(18) Treatment consisted of trastuzumab, 
paclitaxel, carboplatin, gemcitabine, and was feasible. The 
overall response rate was 70% in 44 patients (five 
complete and 26 partial responses) with 57% confirmed 
response rate, which is considered meaningful, especially 
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ECOG-ACRIN 
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in the absence of cisplatin. Median TTP and OS were 9.3 
and 14.1 months, respectively.  
The ECOG Group evaluated the combination of 
trastuzumab with carboplatin/paclitaxel, in patients with 
advanced NSCLC. (19) Toxicity was no worse than 
chemotherapy alone. Overall survival was similar to 
historical data with carboplatin/paclitaxel. However, 
patients with HER2 protein over-expression (+3) did well 
compared to historical data suggesting potential benefit 
with trastuzumab in a target-based selected subset of 
NSCLC patients. 
In a report, two patients with HER2 over-expressing 
progressive or recurrent metastatic endometrial carcinoma 
were treated with trastuzumab after radiation treatment 
and/or salvage chemotherapy.(20) Clinical responses to 
trastuzumab alone or combined with chemotherapy were 
confirmed in both patients by imaging and serum CA-125 
evaluations. These patients experienced symptomatic 
relief and had prolonged survival with no significant 
toxicity. 
1.2 
Pertuzumab 
Pertuzumab is a humanized monoclonal antibody and is the first of a novel class 
of HER2-targeted agents known as HER2 dimerization inhibitors. This agent 
binds to a distinct epitope on the extracellular domain of the HER2 receptor (the 
domain II dimerization arm), blocking the interaction between HER2 and other 
HER family receptors.(21) Potent inhibition of HER-mediated intracellular 
signaling results in cancer cell growth inhibition and death.(22) Pertuzumab has a 
complementary mechanism of action to trastuzumab, in that it inhibits 
HER2/HER3 dimerization, inhibiting HER2-mediated cell signalling via the 
phosphatidylinositol 3-kinase (PI3K/Akt) pathway. Pertuzumab can also trigger 
ADCC-independent of trastuzumab, and with comparable efficacy. (23) 
1.2.1 
Preclinical Studies 
The antitumor activity of pertuzumab and trastuzumab, a HER2-
targeted monoclonal antibody, has been evaluated both as a single 
agent and in combination in HER2-positive breast cancer xenografts. 
The combination of trastuzumab and pertuzumab was found to have a 
greatly enhanced antitumor effect, a result not achieved with 
monotherapy. The enhanced efficacy of the combination was also 
observed after tumor progression during trastuzumab monotherapy 
and may relate to the different mechanisms of action of pertuzumab; 
inhibition of HER2 dimerization and prevention of p95HER2 formation. 
(22) 
It was observed in in vitro studies that pertuzumab inhibits the 
heregulin-induced activation of the PI3K cell survival pathway, 
whereas trastuzumab does not (2). This implied that pertuzumab was 
more effective than trastuzumab in preventing HER2 signaling. 
Activity of single agent pertuzumab in breast, prostate, ovarian and 
lung cancer cell lines was observed in human tumor xenograft models 
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ECOG-ACRIN 
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in mice (2). The combination of pertuzumab and trastuzumab was 
found to have a greatly enhanced antitumor effect in HER2-positive 
breast cancer in vitro studies as well as xenografts, a result not 
achieved with monotherapy (24). 
The antitumor effects of HER2-directed combination therapy with 
trastuzumab and pertuzumab in ovarian cancer xenograft models 
have been demonstrated. (25) The combination of these antibodies 
showed enhanced anti-tumor activity compared to single agent 
therapy. High HER2 expression and increasing HER3 protein 
expression on treatment were associated with response. 
In an in vitro study, pertuzumab and trastuzumab induced equally 
strong ADCC and CDC in FISH-positive uterine serous papillary 
adenocarcinoma cell lines.(26) Pertuzumab significantly increased 
tratuzumab-induced ADCC in uterine serous papillary 
adenocarcinoma with low HER2 expression, implying that it may 
represent a new therapeutic agent in patients with advanced, 
recurrent and/or refractory disease.  
1.2.2 
Clinical Studies 
Pertuzumab was investigated initially as a single agent in metastatic 
breast cancer, with disappointing results. In a study that evaluated 
pertuzumab monotherapy in patients with progressive HER2-negative 
metastatic breast cancer, the ORR was 4.9% and the clinical benefit 
rate (CBR) was 9.8% (n=79). Pertuzumab was relatively well 
tolerated, with most adverse events being mild to moderate. Decline 
LQOHIWYHQWULFXODUHMHFWLRQIUDFWLRQRIDQGRUWRZDV
observed in eight patients, with one case of congestive heart 
failure.(27) In another study in HER2-positive patients with metastatic 
breast cancer progressing on trastuzumab, the ORR was 7.4% with a 
CBR of 11.1% (n=29). Interestingly, if the tumor failed to respond to 
pertuzumab monotherapy or responded and then progressed, 
trastuzumab could be added to pertuzumab. This strategy was 
undertaken in 14 patients, and 2 of these 14 achieved confirmed 
response when trastuzumab was added to the pertuzumab. This was 
the first clinical report providing evidence of an enhanced effect when 
the antibodies are combined.(28) 
1.3 
Dual anti-HER2 Therapy  
1.3.1 
Clinical Studies: Dual anti-HER2 Therapy without chemotherapy 
The combination of pertuzumab and trastuzumab has yielded 
promising results in early phase clinical trials. A phase 2 trial in 
patients with HER2-positive metastatic breast cancer whose disease 
had progressed during prior trastuzumab-based therapy assessed the 
efficacy and safety profile of the combination of pertuzumab and 
trastuzumab (n=66). The ORR was 24.2%, and the CBR was 50%, 
with median PFS of 5.5 months. Cardiac dysfunction was minimal, 
and no patients needed to discontinue therapy as a result of cardiac-
related adverse events.(29) More recently, preliminary results from 
the MyPathway clinical trial were presented at the 2016 ASCO GI 
Symposium, suggesting an ORR of 38% and CBR of 54% with 
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median time to progression 5.6 months in HER-2 overexpressing or 
amplified metastatic colorectal cancer without new safety signals with 
the anti-HER2 combination. (35) This promising response rate in the 
setting of dual anti-HER2 therapy without chemotherapy has also 
been shown with the combination of trastuzumab and lapatinib in the 
HERACLES trial, with a 30% ORR in patients with heavily pre-treated 
HER2-positive and RAS wild type metastatic colorectal cancer. (36) 
1.3.2 
Clinical Studies: Dual anti-HER2 Therapy and Chemotherapy 
This combination of HER2-targeted agents has also been investigated 
in the neoadjuvant setting. NeoSphere was a Phase 2 randomized 
trial of preoperative systemic therapy comparing 
trastuzumab/docetaxel, trastuzumab/pertuzumab/docetaxel, 
trastuzumab/pertuzumab, and pertuzumab/docetaxel. The pCR rates 
were 29%, 46%, 17% and 24% respectively. When patients were 
analyzed based on ER status, a 63% pCR rate was observed in those 
with ER-negative disease treated with 
trastuzumab/pertuzumab/docetaxel and 27% in those with ER-
negative disease treated with trastuzumab/pertuzumab.(30) Based on 
data from NeoSphere and other preoperative studies investigating 
pertuzumab in combination with chemotherapy, the FDA  granted 
accelerated approval in late 2013 to pertuzumab for use 
preoperatively in combination with a complete chemotherapy regimen 
such as that investigated in NeoSphere. 
A phase 3 trial in previously untreated HER2-positive metastatic 
breast cancer  patients (CLEOPATRA), which randomized patients to 
trastuzumab/docetaxel vs trastuzumab/pertuzumab/docetaxel, has 
been presented.(31) The median PFS was 12.4 months in the control 
group compared with 18.5 months in the pertuzumab group (HR for 
progression or death, 0.62; 95% CI, 0.51 to 0.75; P<0.001). The 
interim analysis of overall survival showed a strong trend in favor of 
pertuzumab/trastuzumab/docetaxel.(31) Updated data indicated a 
median OS of 37.6 months (95% CI 34.3-NE [not estimable]) in the 
trastuzumab/docetaxel group but had not been reached (95% CI 42.4-
NE) in the trastuzumab/pertuzumab/docetaxel group (HR 0.66, 95% 
CI 0.52-0.84; p=0.0008).(32) In addition, a phase 1 trial is ongoing 
investigating the combination of trastuzumab, pertuzumab, and 
paclitaxel in patients with metastatic breast cancer. 
1.4 
Summary 
The management of HER2-positive breast cancer has been revolutionized by the 
development of anti-HER2 therapies such as trastuzumab, which is also 
approved for treatment of HER2-overexpressing metastatic gastric/GEJ 
adenocarcinoma. Recent studies indicate that dual anti-HER2 therapy is more 
efficacious than single anti-HER2 therapy, with recent promising data as above 
also suggesting a high ORR of 30-35% in patients with colorectal cancer. A 
variety of tumor types other than breast and gastric/GEJ adenocarcinoma 
demonstrate amplification of the HER2 receptor (Figure 1), which may indicate a 
heavier dependence of the tumor on this pathway than in those tumors without 
amplification. These patients are unlikely to have had prior trastuzumab or 
pertuzumab. Thus, the combination of trastuzumab and pertuzumab may result 
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ECOG-ACRIN 
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in higher response rate and/or prolonged PFS for this group of patients and is 
being investigated in this arm of the NCI MATCH trial in patients with HER2 
amplification. 
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ECOG-ACRIN 
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2. 
Selection of Patients 
Each of the criteria in the checklist that follows must be met, along with the eligibility in 
the MATCH Master Protocol, in order for a patient to be considered eligible for this 
study. Use the checklist to confirm a patient’s eligibility. For each patient, this checklist 
must be photocopied, completed and maintained in the patient’s chart.  
In calculating days of tests and measurements, the day a test or measurement is 
done is considered Day 0. Therefore, if a test is done on a Monday, the Monday 
four weeks later would be considered Day 28.  
ECOG-ACRIN Patient No. ____________________________ 
Patient’s Initials (L, F, M) _______________________ 
Physician Signature and Date ___________________ 
NOTE: 
Policy does not allow for the issuance of waivers to any protocol specified 
criteria (http://ctep.cancer.gov/protocolDevelopment/policies deviations.htm). 
Therefore, all eligibility criteria listed in Section 2 must be met, without 
exception. The registration of individuals who do not meet all criteria listed in 
Section 2 can result in the participant being censored from the analysis of the 
study, and the citation of a major protocol violation during an audit.  All 
questions regarding clarification of eligibility criteria must be directed to the 
Group's Executive Officer (EA.Execofficer@jimmy.harvard.edu) or the 
Group's Regulatory Officer (EA.RegOfficer@jimmy.harvard.edu). 
NOTE: 
Institutions may use the eligibility checklist as source documentation if it has 
been reviewed, signed, and dated prior to registration/randomization by the 
treating physician. 
NOTE: 
All patients must have signed the relevant treatment consent form 
2.1 
Registration to Treatment  
2.1.1 
Patients must fulfill all eligibility criteria outlined in Section 3.1 of 
MATCH Master Protocol (excluding Sections 3.1.6, 3.1.7 and 3.1.11) 
at the time of registration to treatment step (Step 1, 3, 5, 7). 
2.1.2 
Patients must have HER2 amplification, or another aberration, as 
determined via the MATCH Master Protocol and according to 
Appendix I. See Appendix I for information on the targeted mutations 
and corresponding Levels of Evidence. 
2.1.3 
Patients must have an electrocardiogram (ECG) within 8 weeks prior 
to treatment assignment and must have no clinically important 
abnormalities in rhythm, conduction or morphology of resting ECG 
(e.g. complete left bundle branch block, third degree heart block). 
Date of ECG:  _______________ 
2.1.4 
Patients must have ECHO or MUGA within 4 weeks prior to treatment 
assignment and must not have a left ventricular ejection fraction 
(LVEF) < institutional lower limit of normal (LLN). If the LLN is not 
GHILQHGDWDVLWHWKH/9()PXVWEHIRUWKHSDWLent to be 
eligible. 
Date of ECHO/MUGA:  _______________  
_____ 
_____ 
_____ 
_____ 
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2.1.5 
Patients must not have breast cancer, gastric/GEJ/esophageal 
adenocarcinoma or mixed histology, gastric/GEJ NOS tumors, or 
colorectal adenocarcinoma. 
2.1.6 
Patients must not have known hypersensitivity to trastuzumab or 
pertuzumab or compounds of similar chemical or biologic 
composition. 
2.1.7 
Patients must not have received prior anti-HER2 therapies, including 
trastuzumab, pertuzumab, T-DM1, lapatinib, afatinib, neratinib, 
dacomitinib, canertinib. 
2.1.8 
Women of childbearing potential (WOCBP) and men who are sexually 
active with WOCBP must agree to use adequate contraception 
(hormonal or double barrier method of birth control, abstinence) from 
one week prior to study treatment starting, during treatment, and for a 
period of 7 months after the last dose of study treatment. 
 
 
 
 
 
 
Physician Signature 
 
Date 
OPTIONAL: 
This signature line is provided for use by institutions wishing to 
use the eligibility checklist as source documentation. 
 
 
_____ 
_____ 
_____ 
_____ 
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3. 
Trastuzumab and Pertuzumab (HP) Treatment Plan 
3.1 
Administration Schedule 
3.1.1 
Pertuzumab 
Pertuzumab intravenous (IV) will be administered before trastuzumab 
on Day 1 every 3 weeks. Allow 60 minutes between drug 
administration for Cycle 1 and 30 minutes between drugs for 
subsequent cycles. Administer a loading dose of 840 mg on Day 1 
Cycle 1 as a 60-minute intravenous infusion. Subsequent doses of 
420 mg are administered every 3 weeks over 30 or 60 minutes if the 
initial infusion was well tolerated. 
Repeat cycles until progression or unacceptable toxicity. 
3.1.2 
Trastuzumab 
Trastuzumab intravenous (IV) will be administered after pertuzumab 
on Day 1 every 3 weeks. Allow 60 minutes between drug 
administration for Cycle 1 and 30 minutes between drugs for 
subsequent cycles. Administer a loading dose of 8 mg/kg on Day 1 
Cycle 1 as a slow intravenous infusion. Subsequent doses of 6 mg/kg 
are administered every 3 weeks over 30 minutes if the initial infusion 
was well tolerated. 
Repeat cycles until progression or unacceptable toxicity. 
3.2 
Adverse Event Reporting Requirements 
The Adverse Event Reporting Requirements for all EAY131 subprotocols are 
outlined in the MATCH MASTER protocol. Please refer to those guidelines when 
determining if an event qualifies as a Serious Adverse Event (SAE) and requires 
expedited reporting via CTEP’s Adverse Event Reporting System (CTEP-AERS). 
In addition, the following section outlines agent specific requirements and must 
be followed to ensure all reporting requirements are met. 
3.2.1 
Additional instructions, requirements and exceptions for protocol 
EAY131 – Subprotocol J 
Additional Instructions 
For instructions on how to specifically report events that result in 
persistent or significant disability/incapacity, congenital anomaly, 
or birth defect events via CTEP-AERS, please contact the AEMD 
Help Desk at aemd@tech-res.com  or 301-897-7497. This will 
need to be discussed on a case-by-case basis. 
 
EAY131 – Subprotocol J specific expedited reporting 
requirements: 
x 
Cardiac toxicities: Any grade congestive heart failure or 
asymptomatic decline in LVEF requiring treatment or leading to 
discontinuation of pertuzumab and trastuzumab must be 
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reported via CTEP-AERS according to the timeframes outlined 
in the AE table in Section 5.3.6 of the MATCH Master protocol. 
x 
Pregnancies: Pregnancies and suspected pregnancies 
(including a positive or inconclusive pregnancy test, regardless 
of age or disease state) occurring while the female patient is on 
Trastuzumab and Pertuzumab (HP), or within 7 months of the 
female patient’s last dose of Trastuzumab and Pertuzumab 
(HP), are considered immediately reportable events. The 
pregnancy, suspected pregnancy, or positive/ inconclusive 
pregnancy test must be reported via CTEP-AERS within 24 
hours of the Investigator’s knowledge. Please refer to Appendix 
VIII in MATCH Master Protocol for detailed instructions on how 
to report the occurrence of a pregnancy as well as the outcome 
of all pregnancies. 
NOTE: 
The timeframes and requirements for reporting 
pregnancies on this study is longer than the 
standard 28 days as stated in Appendix VIII of the 
MATCH Master Protocol. Please note on this study, 
pregnancies must be reported if they occur within 7 
months of the subjects’ last dose of Trastuzumab 
and Pertuzumab. 
 
EAY131 – Subprotocol J specific expedited reporting 
exceptions: 
For Subprotocol J, the adverse events listed below do not require 
expedited reporting via CTEP-AERS: 
x 
If an AE meets the reporting requirements of the protocol, and 
it is listed on the SPEER, it should ONLY be reported via 
CTEP-AERS if the grade being reported exceeds the grade 
listed in the parentheses next to the event. Since this protocol 
uses multiple investigational agents, if an AE is listed on both 
SPEERs, use the lower of the grades to determine if expedited 
reporting is required. 
3.2.2 
Second Primary Cancer Reporting Requirements 
All cases of second primary cancers, including acute myeloid 
leukemia (AML) and myelodysplastic syndrome (MDS), that occur 
following treatment on NCI-sponsored trials must be reported to 
ECOG-ACRIN using Medidata Rave 
x 
A second malignancy is a cancer that is UNRELATED to any 
prior anti-cancer treatment (including the treatment on this 
protocol). Second malignancies require ONLY routine reporting 
as follows: 
1. Complete a Second Primary Form in Medidata Rave within 14 
days. 
2. Upload a copy of the pathology report to ECOG-ACRIN via 
Medidata Rave confirming the diagnosis. 
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3. If the patient has been diagnosed with AML/MDS, upload a 
copy of the cytogenetics report (if available) to ECOG-ACRIN 
via Medidata Rave. 
x 
A secondary malignancy is a cancer CAUSED BY any prior anti-
cancer treatment (including the treatment on this protocol). 
Secondary malignancies require both routine and expedited 
reporting as follows: 
1. Complete a Second Primary Form in Medidata Rave within 14 
days 
2. Report the diagnosis via CTEP-AERS at http://ctep.cancer.gov  
Report under a.) leukemia secondary to oncology 
chemotherapy, b.) myelodysplastic syndrome, or c.) treatment 
related secondary malignancy 
3. Upload a copy of the pathology report to ECOG-ACRIN via 
Medidata Rave and submit a copy to NCI/CTEP confirming the 
diagnosis. 
4. If the patient has been diagnosed with AML/MDS, upload a 
copy of the cytogenetics report (if available) to ECOG-ACRIN 
via Medidata Rave and submit a copy to NCI/CTEP. 
NOTE: 
The Second Primary Form and the CTEP-AERS report 
should not be used to report recurrence or development of 
metastatic disease. 
NOTE: 
If a patient has been enrolled in more than one NCI-
sponsored study, the Second Primary Form must be 
submitted for the most recent trial. ECOG-ACRIN must be 
provided with a copy of the form and the associated 
pathology report and cytogenetics report (if available) even 
if ECOG-ACRIN was not the patient's most recent trial. 
NOTE: 
Once data regarding survival and remission status are no 
longer required by the protocol, no follow-up data should 
be submitted via CTEP-AERS or by the Second Primary 
Form. 
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a reasonable possibility that trastuzumab (Herceptin) and/or Herceptin HylectaTM (SQ 
trastuzumab) caused the adverse event: 
CARDIAC DISORDERS - Asystole; Atrial fibrillation; Atrial flutter; Chest pain - cardiac; 
Myocardial infarction; Myocarditis; Sinus bradycardia; Ventricular arrhythmia; Ventricular 
tachycardia 
EAR AND LABYRINTH DISORDERS - Hearing impaired; Vertigo 
EYE DISORDERS - Dry eye; Extraocular muscle paresis 
GASTROINTESTINAL DISORDERS - Ascites; Colitis; Constipation; Duodenal ulcer; 
Dyspepsia; Enterocolitis; Esophagitis; Gastric hemorrhage; Gastritis; Gastrointestinal pain; 
Small intestinal perforation; Typhlitis 
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS - Generalized edema; 
Sudden death NOS 
HEPATOBILIARY DISORDERs - Cholecystitis 
INJURY, POISONING AND PROCEDURAL COMPLICATIONS - Dermatitis radiation; Fracture; 
Injury, poisoning and procedural complications - Other (incision site pain); Injury, poisoning and 
procedural complications - Other (procedural pain) 
INVESTIGATIONS - Alanine aminotransferase increased; Creatinine increased; Weight gain; 
White blood cell decreased 
METABOLISM AND NUTRITION DISORDERS - Dehydration; Hyperkalemia; 
Hypoalbuminemia; Hypokalemia; Hyponatremia; Hypophosphatemia 
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS - Arthritis; Chest wall pain; 
Flank pain; Generalized muscle weakness; Neck pain 
NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS) - 
Leukemia secondary to oncology chemotherapy; Treatment related secondary malignancy 
NERVOUS SYSTEM DISORDERS - Amnesia; Depressed level of consciousness; 
Encephalopathy; Leukoencephalopathy; Muscle weakness left-sided; Paresthesia; Seizure; 
Syncope 
PSYCHIATRIC DISORDERS - Anxiety; Confusion 
RENAL AND URINARY DISORDERS - Acute kidney injury; Proteinuria 
REPRODUCTIVE SYSTEM AND BREAST DISORDERS - Amenorrhea 
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS - Epistaxis; Nasal congestion; 
Oropharyngeal pain; Pharyngolaryngeal pain; Pleural effusion4; Pulmonary hypertension; 
Respiratory failure; Wheezing4 
SKIN AND SUBCUTANEOUS TISSUE DISORDERS - Eczema; Erythema multiforme; 
Hyperhidrosis; Palmar-plantar erythrodysesthesia syndrome; Pruritus; Skin hyperpigmentation; 
Stevens-Johnson syndrome 
VASCULAR DISORDERS - Hematoma; Thromboembolic event 
NOTE: 
Trastuzumab (Herceptin) in combination with other agents could cause an 
exacerbation of any adverse event currently known to be caused by the other agent, 
or the combination may result in events never previously associated with either 
agent. 
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INVESTIGATIONS - Alkaline phosphatase increased; Blood bilirubin increased; Creatinine 
increased; GGT increased; Investigations - Other (granulocytopenia); Lymphocyte count 
decreased; Platelet count decreased; Weight gain; Weight loss 
METABOLISM AND NUTRITION DISORDERS - Dehydration; Hyperglycemia; Hypoglycemia; 
Hypokalemia; Hypomagnesemia 
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS - Bone pain; Muscle cramp; 
Musculoskeletal and connective tissue disorder - Other (dermatomyositis syndrome); 
Musculoskeletal and connective tissue disorder - Other (spinal pain) 
NERVOUS SYSTEM DISORDERS - Amnesia; Dysarthria; Lethargy; Nervous system disorders 
- Other (osmotic demyelination syndrome); Somnolence; Syncope 
PSYCHIATRIC DISORDERS - Anxiety; Depression 
RENAL AND URINARY DISORDERS - Acute kidney injury; Dysuria; Urinary frequency 
REPRODUCTIVE SYSTEM AND BREAST DISORDERS - Amenorrhea; Breast pain; Irregular 
menstruation; Reproductive system and breast disorders - Other (metrorrhagia); Vaginal 
dryness 
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS - Bronchospasm4; Nasal 
congestion; Oropharyngeal pain; Pleural effusion; Pneumonitis; Postnasal drip; Respiratory 
failure; Respiratory, thoracic and mediastinal disorders - Other (painful respiration); Rhinorrhea 
SKIN AND SUBCUTANEOUS TISSUE DISORDERS - Erythema multiforme; Erythroderma; 
Hyperhidrosis; Nail discoloration; Pain of skin; Rash acneiform; Skin and subcutaneous tissue 
disorders - Other (onycholysis); Skin and subcutaneous tissue disorders - Other 
(onychomadesis); Skin hyperpigmentation; Urticaria 
VASCULAR DISORDERS - Flushing; Hypertension; Hypotension; Lymphedema; 
Thromboembolic event; Vascular disorders - Other (hyperemia) 
NOTE: 
Pertuzumab in combination with other agents could cause an exacerbation of any 
adverse event currently known to be caused by the other agent, or the combination 
may result in events never previously associated with either agent. 
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3.5 
Dose Modifications  
All toxicity grades below are described using the NCI Common Terminology 
Criteria for Adverse Events (CTCAE) version 4.0. 
All appropriate treatment areas should have access to a copy of the CTCAE 
version 4.0. A copy of the CTCAE version 4.0 can be downloaded from the 
CTEP website (http://ctep.cancer.gov). 
Dose modification of pertuzumab and trastuzumab is not permitted. 
If possible, symptoms should be managed with best supportive care. In case of 
toxicity, appropriate medical treatment should be used (including anti-emetics for 
nausea/vomiting, anti-diarrheals for diarrhea, etc.). No dose escalation is planned 
for this study. 
A new cycle of treatment may begin when the following are met: 
-All non-KHPDWRORJLFWR[LFLW\LPSURYHGWR*UDGH 2 (or to baseline) 
-$1&PP3 DQGSODWHOHWVPP3 
For any event, which is apparent at baseline, the dose delays will apply 
according to the corresponding shift in toxicity grade, if the investigator feels it is 
appropriate. (e.g. if a patient has grade 1 asthenia at baseline which increases to 
grade 2 during treatment, this will be considered as a shift of 1 grade and treated 
as a grade 1 toxicity for dose delay purposes). 
A cycle may be delayed as noted below.  
For delayed or missed doses, if the time between 2 sequential infusions is less 
than 6 weeks, the 420 mg IV dose of pertuzumab should be administered. Do not 
wait until the next planned dose. If the time between 2 sequential infusions is 6 
weeks or more, the initial dose of 840 mg pertuzumab should be re-administered 
as a 60 minute IV infusion followed every 3 weeks thereafter by a dose of 420 
mg IV administered over 30-60minutes. 
Pertuzumab should be withheld or discontinued if trastuzumab treatment is 
withheld or discontinued. Trastuzumab may continue if pertuzumab is withheld or 
discontinued. 
3.5.1 
Toxicity Management for Trastuzumab and Pertuzumab 
Dose delays and recovery windows refer to date of planned dose, not 
since last dose. For example: if cycle 2 was to start on January 1st, but 
is delayed due to grade 3 ANC; you may hold treatment up to 
additional 3 weeks from the originally planned cycle 2 day 1. 
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Figure 4: Algorithm for Continuation/Discontinuation of Study Therapy in Asymptomatic Patients 
Based on LVEF Assessment 
 
NOTE: 
7KH/9() 50% and < 50% refers to the current LVEF. For example: if the 
current LVEF is < 50%, but did not drop at least 10 points from baseline, continue 
treatment and repeat LVEF in 3 weeks. If repeat LVEF still has not dropped at 
least 10 points, continue treatment and repeat LVEF at next scheduled time 
SRLQW,I/9()KDVGURSSHG 10 points on repeat, continue treatment and repeat 
LVEF in another 3 weeks. If LVEF at that time is confirmed as having dropped  
 10 points AND LVEF is < 50%, stop treatment.   
NOTE: 
The Subprotocol Chair must be notified if an assessment of LVEF is performed 
prior to the planned assessment after 12 weeks of therapy so guidance can be 
given if necessary. 
3.5.2 
Important Toxicities for Trastuzumab and Pertuzumab  
3.5.2.1 
Infusion-Associated Reactions (IAR) 
Like other monoclonal antibodies, pertuzumab has been 
associated with infusion associated reaction (such as 
chills, diarrhea, fatigue, headache, nausea, and pyrexia), 
and with hypersensitivity reactions. Close observation of 
the patient during and for 60 minutes after the first infusion 
and during and for 30 minutes following subsequent 
infusions is recommended following the administration of 
pertuzumab. If a significant IAR occurs, the infusion should 
be slowed down or interrupted and appropriate medical 
therapies should be administered. Patients should be 
evaluated and carefully monitored until complete resolution 
of signs and symptoms. Permanent discontinuation should 
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be considered in patients with severe infusion reactions. 
This clinical assessment should be based on the severity 
of the preceding reaction and response to administered 
treatment for the adverse reaction. 
3.5.2.2 
Serious Infusion-Associated Events 
Serious adverse reactions to trastuzumab infusion 
including dyspnea, hypotension, wheezing, bronchospasm, 
tachycardia, reduced oxygen saturation, and respiratory 
distress have been reported infrequently. In rare cases (4 
per 10,000), these events were associated with a clinical 
course culminating in a fatal outcome. Serious reactions 
have been treated with supportive therapy such as oxygen, 
beta-agonists, corticosteroids and withdrawal of 
trastuzumab as indicated. 
3.5.2.3 
Respiratory Symptoms 
A low rate of respiratory events that are compatible with an 
IAR or hypersensitivity reaction/anaphylaxis has been 
reported. Although pertuzumab targets the HER2 receptor 
it inhibits heterodimerization with other members of the 
HER family (eg, EGFR [HER1]). Accordingly, it may cause 
toxicities associated with the use of EGFR inhibitors, such 
as interstitial lung disease (ILD). The few reports of ILD 
occurring in pertuzumab-treated patients received so far 
also had evidence of alternative causes, e.g., concomitant 
medication, preceding/concurrent neutropenia with 
potential infection or relevant medical history. 
3.5.2.4 
Left Ventricular Dysfunction 
Decreases in LVEF have been reported with drugs that 
block HER2 activity. Trastuzumab and pertuzumab both 
target HER2, thus there is a risk of cardiac dysfunction with 
these agents. In the CLEOPATRA pivotal trial, pertuzumab 
in combination with trastuzumab and docetaxel was not 
associated with increases in the incidence of symptomatic 
LVSD or decreases in LVEF compared with placebo in 
combination with trastuzumab and docetaxel.(31) 
Pertuzumab combined with trastuzumab and 
chemotherapy did not result in any significantly greater 
incidence of symptomatic LVSD or decreases in LVEF 
than trastuzumab and chemotherapy in patients with early 
breast cancer.(33) However, in the pivotal MBC trial a 
greater proportion of patients who developed symptomatic 
LVSD had received prior anthracyclines and/or 
radiotherapy compared to the proportion of patients 
receiving prior anthracyclines and/or radiotherapy in the 
overall pertuzumab-treated population.(31) Therefore, 
patients who have received prior anthracyclines or prior 
radiotherapy to the chest area may be at higher risk of 
decreased LVEF.   
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Pertuzumab has not been studied in patients with: a 
SUHWUHDWPHQW/9()YDOXHRIDSULRUKLVWRU\RI&+)
decreases in LVEF to < 50% during prior trastuzumab 
adjuvant therapy; conditions that could impair left 
ventricular function such as uncontrolled hypertension, 
recent myocardial infarction, serious cardiac arrhythmia 
requiring treatment or a cumulative prior anthracycline 
exposure to > 360mg/m2 of doxorubicin or its equivalent. 
3.5.2.5 
Management of Cardiac Safety 
All patients must have a baseline evaluation of cardiac 
function including a measurement of LVEF by either 
MUGA or ECHO prior to entry into the study. Only patients 
ZLWKDQ/9()ZLOOEHHQWHUHGLQWRWKLVVWXG\ 
It is recommended that patients should have cardiac 
monitoring at regular intervals (e.g., every three months) 
during treatment with pertuzumab and trastuzumab. As 
part of this study, cardiac monitoring will occur at baseline 
and at conclusion of study treatment (i.e., after about 3 
months); or additionally if required to monitor toxicity.  
ECHO or MUGA scans should be scheduled at the same 
radiology facility where the patient’s baseline ECHO or 
MUGA was conducted. When a cardiac event occurs, the 
Cardiac Report Form must be submitted within 14 days of 
learning of the event.   
During the course of trastuzumab and pertuzumab therapy, 
patients should be monitored for signs and symptoms of 
CHF (i.e., dyspnea, tachycardia, new unexplained cough, 
neck vein distention, cardiomegaly, hepatomegaly, 
paroxysmal nocturnal dyspnea, orthopnea, peripheral 
edema, and rapid unexplained weight gain). The 
confirmation of the CHF diagnosis should include the same 
method used to measure LVEF at baseline (either ECHO 
or MUGA). 
Pertuzumab and trastuzumab should be discontinued in 
any patient who develops clinical signs and symptoms 
suggesting CHF. CHF should be treated and monitored 
according to standard medical practice. At present, there 
are inadequate data available to assess the prognostic 
significance of asymptomatic drops in LVEF. 
3.5.2.6 
EGFR-Associated Toxicities 
Although pertuzumab targets the HER2 receptor, it inhibits 
heterodimerization with other members of the HER family 
(e.g., EGFR [HER1]). Accordingly, it may cause toxicities 
associated with the use of EGFR inhibitors such as 
diarrhea, rash and other dermatologic toxicities (eg, dry 
skin, pruritus, nail disorders, mucositis). 
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3.5.2.7 
Diarrhea 
In the 7-week IV and 26-week toxicity studies in 
cynomolgus monkeys, there was a treatment-related 
increase in the incidence of diarrhea. Diarrhea has been 
observed in approximately 60% of patients (treatment-
related diarrhea in 50% of patients) being treated with 
pertuzumab in phase 2 single-agent studies, and up to 
approximately 70% of patients in combination therapy 
studies. Diarrhea was CTCAE Grade 1 or 2 in the majority 
of cases. To prevent dehydration, early treatment of 
diarrhea with anti-diarrheal medication should be 
considered and patients treated with fluids and electrolyte 
replacement, as clinically indicated.  
3.5.2.8 
Rash 
Rash has also been observed with EGFR inhibitors, mostly 
of mild to moderate intensity. Rash has been observed in 
approximately 17% of patients receiving pertuzumab in 
Phase 2 single-agent studies and up to 73% of patients in 
combination studies. The rash was generally of CTCAE 
Grade 1 or 2 in severity. Treatment recommendations for 
EGFR-associated rash include topical or oral antibiotics, 
topical pimecrolimus, topical or (for severe reactions) 
systemic steroids. These agents may be used in patients 
experiencing pertuzumab-related rash, as clinically 
indicated, although they have not been studied in this 
context. 
3.6 
Supportive Care 
All supportive measures consistent with optimal patient care will be given 
throughout the study. 
The administration of any other therapies intended to treat the primary cancer 
including endocrine therapy, chemotherapy, immunotherapy, radioactive and 
biologic/targeted agents is NOT permitted. However, patients with prostate 
cancer may continue on GnRH agonist (or antagonist) with approval by the 
Protocol Chair (oral anti-androgens [e.g. enzalutamide, bicalutamide, flutamide, 
nilutamide], abiraterone, ketoconazole, estrogen are not allowed for prostate 
cancer). Similarly, the use of other concurrent investigational drugs is not 
allowed. Local therapy to sites of disease may be allowed on study (e.g., 
radiation to bone metastases, stereotactic surgery) at the discretion of the 
Protocol Chair, as long as is not the only lesion being monitored for response. 
3.6.1 
Bone-modifying agents 
Patients may be treated with bone modifying agents such as 
bisphosphonates or RANK-ligand agents (e.g. denosumab) per ASCO 
guidelines. Whenever possible, patients requiring bone modifying 
agents should start treatment 7 days prior to study therapy and should 
continue the same agent throughout study unless clinically compelled 
to change. 
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3.7 
Duration of Agent-specific treatment  
In the absence of treatment delays due to adverse event(s), treatment may 
continue until one of the following criteria applies: 
x 
Extraordinary Medical Circumstances: If at any time the constraints of this 
protocol are detrimental to the patient's health, protocol treatment should be 
discontinued. In this event submit forms according to the instructions in the 
MATCH Forms Packet. 
x 
Patient withdraws consent. 
x 
Patient experiences unacceptable toxicity. 
x 
Non-protocol therapies are administered. 
x 
Disease progression 
3.8 
Duration of Follow-Up 
Refer to the MATCH Master Protocol for specifics on the duration of follow-up. 
 
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4. 
Study Parameters 
4.1 
Therapeutic Parameters for Trastuzumab and Pertuzumab Treatment  
NOTE: 
In addition to the study parameters listed in the MATCH Master Protocol, the below parameters must also be 
performed for patients receiving Trastuzumab and Pertuzumab treatment. 
NOTE: 
$OODVVHVVPHQWVUHTXLUHGSULRUWRUHJLVWUDWLRQWRWUHDWPHQWVKRXOGEHGRQHZHHNVSULRUWRUHJLVWUDWLRQWR
Steps 1, 3, 5, 7, excluding the radiologic evaluation and electrocardiogram (ECG). 
NOTE:  
The schedule should be followed as closely as is realistically possible; however, the schedule may be 
modified due to problems such as scheduling delays or conflicts (e.g., clinic closure, poor weather conditions, 
vacations, etc.) with the guidance of the Protocol Chair/designee, as appropriate, and will not be reportable 
as a deviation unless the endpoints of the study are affected. 
Test/Assessment 
Prior to Registration to 
Treatment 
Treatment 
End of 
Treatment 
Follow UpL 
Every Cycle, prior 
to treatment 
Every 3 
Cycles 
H&P, Weight, Vital signsA 
X 
 XK 
 
 
X 
Performance status 
X 
 XK 
 
 
X 
Concomitant Medication ReviewB 
 
 
 
 
 
CBC w/diff, pltsC 
X 
 XK 
 
 
X 
Serum chemistryC 
X 
 XK 
 
 
X 
Radiologic evaluationD 
X 
 
 XD 
 
 XL 
E-HCGE 
X 
 
 
 
 
Toxicity AssessmentF 
 
X 
 
X 
 XL 
ECGG 
 XJ 
  
 
 
 
ECHO/Nuclear StudyH 
 XH 
 
 
 XH 
 
Tumor biopsy and blood sample for MATCH Master ProtocolI 
 
 
X 
X 
 
A. History and physical, including vital signs and weight at the start of each cycle (up to 3 days before start of new cycle). 
B. Concomitant Medications will be collected up to 90 days from the end of study treatment. 
C. Albumin, alkaline phosphatase, total bilirubin, bicarbonate, BUN, calcium, creatinine, glucose, phosphorus, potassium, SGOT[AST], SGPT[ALT], 
sodium (magnesium as clinically indicated). For eligibility purposes, participants with creatinine levels above institutional normal, Cockcroft-Gault 
will be used to calculate creatinine clearance, as clinically indicated. CBC w/diff, platelets and serum chemistries should be performed on cycle 
1, day 1 (or up to 7 days prior), and at the start of each subsequent cycle (up to 3 days before start of new cycle) if clinically indicated (see foot 
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note J).  CBC with differential will be performed more frequently in patients with grade 4 neutropenia or thrombocytopenia until resROXWLRQWR
grade 3. CBC and serum chemistries are only required in follow-up until values return to pre-treatment levels or until progressive disease. 
D. Disease measurements are repeated every 3 cycles for the first 33 cycles, and every 4 cycles thereafter until PD or start of another MATCH 
treatment step. The baseline evaluation should be performed as closely as possible to the beginning of treatment and never more than 6 weeks 
before registration to treatment step. For multiple myeloma patients, please refer to Section 6.4 of the MATCH Master Protocol for additional 
information on myeloma response criteria and the required disease assessments. Documentation (radiologic) must be provided for patients 
removed from study for progressive disease. 
E. Blood pregnancy test (women of childbearing potential) required prior to beginning treatment. 
F. Site personnel should evaluate for toxicity and discuss treatment compliance with the patient in order to ensure the medication is taken correctly; 
this evaluation may be conducted by telephone or in person. The Toxicity Assessment is not required prior to Cycle 1, but is required every 
subsequent cycle. 
G. As clinically indicated.  
H. ECHO/Nuclear Study should be repeated every 12 weeks from Cycle 1 Day 1 (±1 week) while on therapy and at discontinuation unless done in 
the prior 4 weeks. 
I. 
Additional blood specimens and/or biopsies are to be submitted from consenting patients per Section 9.3.2 of the MATCH Master Protocol. 
Submit at the following time points, as applicable: 
x 
Blood specimens are to be submitted at the end of Cycle 2 (prior to start of Cycle 3 treatment). If patient progresses or treatment is 
discontinued prior to Cycle 3, collect the blood at that time instead. On-treatment kits for blood sample collections will be automatically 
shipped to sites upon registration to the treatment step. 
x 
Screening biopsies for additional aMOI assessments after registration to appropriate screening step, if applicable (Step 2 or Step 4). 
x 
At end of all MATCH study treatments, blood specimens and/or research biopsy after consent and registration to Step 8 
Please refer to Section 4 of the MATCH Master Protocol to determine whether the patient proceeds to the next screening step or to follow-up 
(with a potential end of treatment biopsy for research purposes on Step 8). Samples are to be submitted as outlined in Section 9 of the MATCH 
Master Protocol. To order Step 2/4 Screening or Step 8 kits, complete the EAY131 Collection and Shipping Kit Order Form (See Appendix XII of 
the MATCH Master Protocol) and fax to 713-563-6506. 
J. Within 8 weeks of treatment assignment. 
K. For Cycle 1, if the following tests/assessments occurred within 7 days of Day 1, they do not need to be repeated at this timepoint: H&P, Weight, 
Vital Signs; Performance Status; CBC w/diff, plts; Serum chemistry; Concomitant Medications.  
L. Every 3 months if patient is < 2 years from study entry, and every 6 months for year 3. Toxicity assessments and radiologic evaluations are not 
required to be done during Follow Up if progression has been previously reported; however if an adverse event occurs post treatment that meets 
the SAE reporting requirements, it still must be reported via CTEP-AERS, even if progression has occurred. 
 
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5. 
Drug Formulation and Procurement 
This information has been prepared by the ECOG-ACRIN Pharmacy and Nursing 
Committees. 
Availability 
NO STARTER SUPPLIES MAY BE ORDERED. Subjects must be enrolled and assigned 
to the treatment subprotocol prior to submitting the clinical drug request to PMB. 
Drug Ordering: NCI supplied agents may be requested by eligible participating 
Investigators (or their authorized designee) at each participating institution.  
Pharmaceutical Management Branch (PMB) policy requires that drug be shipped directly 
to the institution where the patient is to be treated. PMB does not permit the transfer of 
agents between institutions (unless prior approval from PMB is obtained – see general 
information) The CTEP-assigned protocol number must be used for ordering all CTEP-
supplied investigational agents.  The eligible participating investigators at each 
participating institution must be registered with CTEP, DCTD through an annual 
submission of FDA Form 1572 (Statement of Investigator), NCI Biosketch, Agent 
Shipment Form, and Financial Disclosure Form (FDF). If there are several participating 
investigators at one institution, CTEP-supplied investigational agents for the study 
should be ordered under the name of one lead investigator at that institution. 
Submit agent requests through the PMB Online Agent Order Processing (OAOP) 
application (https://ctepcore.nci.nih.gov/OAOP). Access to OAOP requires the 
establishment of a CTEP Identity and Access Management (IAM) account 
(https://ctepcore.nci.nih.gov/iam/) and the maintenance of an “active” account status, a 
“current” password, and an active person registration status. 
NCI Supplied Agent(s) – General Information 
Questions about drug orders, transfers, returns, or accountability should be 
addressed to the PMB by calling 240-276-6575 Monday through Friday between 
8:30 AM and 4:30 PM Eastern Time or email PMBAfterHours@mail.nih.gov 
anytime. 
Drug Returns: All undispensed drug supplies should be returned to the PMB. When it is 
necessary to return study drug (e.g., sealed bottles remaining when PMB sends a stock 
recovery letter), investigators should return the study drug to the PMB using the NCI 
Return Agent Form available on the NCI home page (http://ctep.cancer.gov). 
Drug Accountability: The investigator, or a responsible party designated by the 
investigator, must maintain a careful record of the receipt, disposition, and return of 
agent received from the PMB using the NCI Investigational Agent Accountability Record 
Form for Oral Agents available on the NCI home page (http://ctep.cancer.gov). Maintain 
separate NCI Investigational Agent Accountability Records for each agent, strength, 
formulation and ordering investigator. 
Investigator Brochure Availability: The current versions of the IBs for PMB-supplied 
agents will be accessible to site investigators and research staff through the PMB Online 
Agent Order Processing (OAOP) application. Access to OAOP requires the 
establishment of a CTEP Identity and Access Management (IAM) account and the 
maintenance of an “active” account status, a “current” password, and active person 
registration status.  Questions about IB access may be directed to the PMB IB 
coordinator at IBCoordinator@mail.nih.gov. 
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5.1 
Trastuzumab (NSC #688097) 
5.1.1 
Other Names  
HERCEPTIN®; rhuMAb HER-2/NEU; MoAb HER2/NEU 
5.1.2 
Classification  
Monoclonal antibody 
5.1.3 
Mode of Action  
The HER2 (or c-erbB2) proto-oncogene encodes a transmembrane 
receptor protein of 185 kDa, which is structurally related to the 
epidermal growth factor receptor. Trastuzumab has been shown, in 
both in vitro assays and in animals, to inhibit the proliferation of 
human tumor cells that overexpress HER2. 
Trastuzumab is a mediator of antibody-dependent cellular cytotoxicity 
(ADCC). In vitro, Herceptin-mediated ADCC has been shown to be 
preferentially exerted on HER2 overexpressing cancer cells compared 
with cancer cells that do not overexpress HER2. 
5.1.4 
How Supplied 
Genentech supplies and the Pharmaceutical Management Branch, 
CTEP, NCI, distributes trastuzumab in a multi-use vial containing 440 
mg trastuzumab as a lyophilized sterile powder, under vacuum. Each 
carton contains one vial Herceptin® and one vial (20 mL) of 
Bacteriostatic Water for Injection (BWFI), USP, containing 1.1% 
benzyl alcohol as a preservative. 
Trastuzumab is a sterile, white to pale yellow, preservative-free 
lyophilized powder for intravenous administration. Each multi-use vial 
RIWUDVWX]XPDEFRQWDLQVPJWUDVWX]XPDEPJĮĮ-trehalose 
dihydrate, 9.9 mg L-histidine HCl, 6.4 mg L-histidine, and 1.8 mg 
polysorbate 20, USP. 
In the first half of 2019, NCI will switch over to start supplying only 
single-use 150 vials of trastuzumab as a lyophilized preparation for 
parenteral administration. The commercially-labeled 150 mg vials are 
formulated in histidine/histidine-HCl monohydrate, D,D-trehalose 
dihydrate, and polysorbate 20. NOTE: The 150 mg vials are not 
multi-use vials. 
5.1.5 
Storage and Stability  
Storage: VWRUHDWí&í)SULRUWRUHFRQVWLWXWLRQ 
Stability: Do not use beyond the expiration date stamped on the 
product label (440 mg kit box or 150 mg vial).  The 440 mg vial of 
trastuzumab reconstituted with BWFI, as supplied, is stable for 28 
GD\VDIWHUUHFRQVWLWXWLRQZKHQVWRUHGUHIULJHUDWHGDWí&í). 
Discard any remaining multi-dose reconstituted solution after 28 days.  
A vial of trastuzumab reconstituted with unpreserved SWFI (not 
supplied) should be used immediately and any unused portion 
discarded.  Do Not Freeze trastuzumab following reconstitution or 
dilution. 
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The solution of trastuzumab for infusion diluted in polyvinylchloride or 
polyethylene bags containing 0.9% Sodium Chloride Injection, USP, 
VKRXOGEHVWRUHGDWí&í)IRUQRPRUHWKDQKRXUVSULRU
to use. 
Either multi-dose or single dose handling is allowed at institutional 
discretion. 
5.1.6 
Dose Specifics  
Trastuzumab intravenous (IV) will be administered after pertuzumab 
on Day 1 every 3 weeks. Allow 60 minutes between drug 
administration for Cycle 1 and 30 minutes between drugs for 
subsequent cycles. Administer a loading dose of 8 mg/kg on Day 1 
Cycle 1 as a slow intravenous infusion. Subsequent doses of 6 mg/kg 
are administered every 3 weeks over 30 minutes if the initial infusion 
was well tolerated. 
5.1.7 
Preparation  
Reconstitute each 440 mg vial of trastuzumab with 20 mL of 
Bacteriostatic Water for Injection (BWFI), USP, containing 1.1% 
benzyl alcohol as a preservative to yield a multi-dose solution 
containing 21 mg/mL trastuzumab. 
Reconstitute each 150 mg vial of trastuzumab with 7.4 mL of Sterile 
Water for Injection (SWFI), USP to yield a solution containing 
approximately 21 mg/mL trastuzumab at a pH of approximately 6.0.  
Use of other reconstitution solvents should be avoided. A volume 
overfill ensures that the labeled dose of 150 mg can be withdrawn 
from each vial. 
Reconstitution 
Use appropriate aseptic technique when performing the following 
reconstitution steps: 
440 mg vials 
x 
Using a sterile syringe, slowly inject the 20 mL of diluent into the 
vial containing the lyophilized cake of trastuzumab. The stream of 
diluent should be directed into the lyophilized cake. 
x 
Swirl the vial gently to aid reconstitution. DO NOT SHAKE. 
x 
Slight foaming of the product may be present upon reconstitution. 
Allow the vial to stand undisturbed for approximately 5 minutes. 
x 
Parenteral drug products should be inspected visually for 
particulate matter and discoloration prior to administration, 
whenever solution and container permit. Inspect visually for 
particulates and discoloration. The solution should be free of 
visible particulates, clear to slightly opalescent and colorless to 
pale yellow. 
x 
6WRUHUHFRQVWLWXWHGWUDVWX]XPDEDWí&GLVFDUGXQXVHG
trastuzumab after 28 days. If trastuzumab is reconstituted with 
SWFI without preservative, use immediately and discard any 
unused portion. 
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150 mg vials 
x 
Using a sterile syringe, slowly inject the 7.4 mL of Sterile Water for 
Injection (SWFI), USP into the vial containing the lyophilized cake 
of trastuzumab. The stream of diluent should be directed into the 
lyophilized cake. 
x 
Swirl the vial gently to aid reconstitution. DO NOT SHAKE. 
x 
Slight foaming of the product may be present upon reconstitution. 
Allow the vial to stand undisturbed for approximately 5 minutes. 
x 
Parenteral drug products should be inspected visually for 
particulate matter and discoloration prior to administration, 
whenever solution and container permit. Inspect visually for 
particulates and discoloration. The solution should be free of 
visible particulates, clear to slightly opalescent and colorless to 
pale yellow. 
x 
Single-use vial should be used immediately after reconstitution. 
Dilution 
x 
Determine the dose (mg) of trastuzumab. Calculate the volume of 
the 21 mg/mL reconstituted trastuzumab solution needed, 
withdraw this amount from the vial and add it to an infusion bag 
containing 250 mL of 0.9% Sodium Chloride Injection, USP. DO 
NOT USE DEXTROSE (5%) SOLUTION. 
x 
Gently invert the bag to mix the solution. 
5.1.8 
Route of Administration  
Intravenous infusion through standard IV tubing 
5.1.9 
Incompatibilities 
The mean serum trough concentration of trastuzumab was 
consistently elevated approximately 1.5-fold, when administered in 
combination with paclitaxel as compared to trough concentrations of 
trastuzumab when administered in combination with an anthracycline 
and cyclophosphamide. 
In other pharmacokinetic studies, where trastuzumab was 
administered in combination with paclitaxel, docetaxel, carboplatin, or 
doxorubicin, trastuzumab did not alter the plasma concentrations of 
these chemotherapeutic agents, or the metabolites that were 
analyzed. In a drug interaction substudy conducted in patients, the 
pharmacokinetics of cisplatin, capecitabine and their metabolites were 
not altered when administered in combination with trastuzumab. 
5.1.10 
Side Effects  
See Section 3.3 for side effects. 
5.1.11 
Nursing/Patient Implications  
The initial dose should be administered over approximately 90 
minutes. If this is well tolerated, subsequent administration may be 
infused over approximately 30 minutes. DO NOT ADMINISTER AS 
AN IV PUSH OR BOLUS. 
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Premedication regimens standard to each institution are suggested. 
This may include acetaminophen and diphenhydramine, for example. 
Each institution may employ the premedication regimens considered 
routine in their practices. The regimens used should be clearly noted 
in the medical record and research file. 
See Section 3.5.2 for management of infusion-associated reactions 
(IARs) and other specific toxicities. 
5.2 
Pertuzumab (NSC #740102) 
5.2.1 
Other Names  
PERJETA® 
5.2.2 
Classification  
HER2/neu receptor antagonist 
5.2.3 
Mode of Action  
Pertuzumab blocks ligand-dependent heterodimerization of HER2 
with other HER family members, including EGFR, HER3, and HER4. 
As a result, pertuzumab inhibits ligand-initiated intracellular signaling 
through two major signal pathways, mitogen-activated protein (MAP) 
kinase, and phosphoinositide 3-kinase (PI3K). Inhibition of these 
signaling pathways can result in cell growth arrest and apoptosis, 
respectively. In addition, pertuzumab mediates antibody-dependent 
cell-mediated cytotoxicity (ADCC). 
5.2.4 
How Supplied 
Pertuzumab is supplied by Genentech, Inc. and distributed by CTEP, 
DCTD, NCI. Pertuzumab is a sterile, clear to slightly opalescent, 
colorless to pale brown liquid for intravenous infusion.  Each single 
use vial contains 420 mg of pertuzumab at a concentration of 30 
mg/mL (14mL) in 20 mM L-histidine acetate (pH 6.0), 120 mM 
sucrose and 0.02% polysorbate 20. 
5.2.5 
Storage and Stability  
Storage: 6WRUHYLDOVLQDUHIULJHUDWRUDW&WR&)WR)XQWLO
time of use. Keep vial in the outer carton in order to protect from light. 
DO NOT FREEZE. DO NOT SHAKE. 
Stability: If the diluted infusion solution is not used immediately, it can 
be stored at &WR&IRUXSWRKRXUVDilute with 0.9% Sodium 
Chloride injection only. 
Diluted pertuzumab has been shown to be stable for up to 24 hours at 
DWHPSHUDWXUHXSWR&+RZHYHUVLQFHGLOXWHGSHUWX]XPDE
contains no preservative, the diluted solution should be stored 
UHIULJHUDWHG&–& 
5.2.6 
Dose Specifics  
Pertuzumab intravenous (IV) will be administered before trastuzumab 
on Day 1 every 3 weeks. Allow 60 minutes between drug 
administration for Cycle 1 and 30 minutes between drugs for 
subsequent cycles. Administer a loading dose of 840 mg on Day 1 
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Cycle 1 as a 60-minute intravenous infusion. Subsequent doses of 
420 mg are administered every 3 weeks over 30 or 60 minutes if the 
initial infusion was well tolerated. 
5.2.7 
Preparation  
Administer as an intravenous infusion only. Do not administer as an 
intravenous push or bolus. Do not mix pertuzumab with other drugs. 
Prepare the solution for infusion, using aseptic technique, as follows: 
x 
Parenteral drug products should be inspected visually for 
particulates and discoloration prior to administration. 
x 
Withdraw the appropriate volume of pertuzumab solution from the 
vial(s). 
x 
Dilute into a 250 mL 0.9% sodium chloride PVC or non-PVC 
polyolefin infusion bag. 
x 
Mix diluted solution by gentle inversion. Do not shake. 
x 
Administer immediately once prepared. 
5.2.8 
Route of Administration  
Intravenous through standard IV tubing 
5.2.9 
Method of Administration 
The initial pertuzumab dose is administered as an approximately 60-
minute intravenous infusion. Subsequent doses are administered by 
intravenous infusion over approximately 30 or 60 minutes, depending 
on how the initial dose was tolerated. 
5.2.10 
Incompatibilities 
Do not use dextrose (5%) solution. 
5.2.11 
Side Effects  
See Section 3.4 for side effects. 
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6. 
Translational Studies 
These may include, but not limited to, immunohistochemistry, fluorescent in situ 
hybridization (FISH) in tumor tissue, as well as assessment of correlation with gene 
amplification by sequencing, evaluation of other tissue biomarkers, additional collection 
of blood (e.g. circulating biomarkers, tumor cells, nucleic acids), others. Additional 
studies will be discussed with MATCH team and may require amendment to protocol.  
Please also refer to the MATCH Master Protocol for information on the Translational 
Studies.  
7. 
References 
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11. Cobleigh MA, Vogel CL, Tripathy D, et al. Multinational study of the efficacy and 
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13. Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal 
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14. Marty M, Cognetti F, Maraninchi D, et al. Randomized phase II trial of the efficacy 
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treatment: the M77001 study group. J Clin Oncol. 2005;23(19):4265-4274. 
15. Perez EA, Romond EH, Suman VJ, et al. Four-Year Follow-Up of Trastuzumab Plus 
Adjuvant Chemotherapy for Operable Human Epidermal Growth Factor Receptor 2-
Positive Breast Cancer: Joint Analysis of Data From NCCTG N9831 and NSABP B-
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operable HER2-positive breast cancer. N Engl J Med. 2005;353(16):1673-1684. 
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chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353(16):1659-
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and gemcitabine in advanced human epidermal growth factor receptor-2/neu-positive 
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in patients with advanced or recurrent endometrial carcinoma overexpressing 
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21. Franklin MC, Carey KD, Vajdos FF, Leahy DJ, de Vos AM, Sliwkowski MX. Insights 
into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer 
Cell. 2004;5(4):317-328. 
22. Scheuer W, Friess T, Burtscher H, Bossenmaier B, Endl J, Hasmann M. Strongly 
enhanced antitumor activity of trastuzumab and pertuzumab combination treatment 
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23. Scheuer W, Friess T, Burtscher  H,et al. Strongly enhanced antitumor activity of  
trastuzumab and pertuzumab combination treatment on HER2-positive human  
xenograft tumor models. Cancer Research.  2009;69(24):9330–9336. 
24. Nahta R, Hung MC, Esteva FJ. The HER-2-targeting antibodies trastuzumab and 
pertuzumab synergistically inhibit the survival of breast cancer cells. Cancer Res. 
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25. Faratian D, Zweemer AJ, Nagumo Y, et al. Trastuzumab and pertuzumab produce 
changes in morphology and estrogen receptor signaling in ovarian cancer xenografts 
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26. El-Sahwi K, Bellone S, Cocco E, et al. In vitro activity of pertuzumab in combination 
with trastuzumab in uterine serous papillary adenocarcinoma. Br J Cancer. 
2010;102(1):134-143. 
27. Gianni L, Llado A, Bianchi G, et al. Open-label, phase II, multicenter, randomized 
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epidermal growth factor receptor 2 dimerization inhibitor, in patients with human 
epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 
2010;28(7):1131-1137. 
28. Cortés J, Baselga J, Petrella T, et al. Pertuzumab monotherapy following 
trastuzumab-based treatment: Activity and tolerability in patients with advanced 
HER2- positive breast cancer. Presented at the American Society of Oncology 
Meeting 2009. J Clin Oncol 27:15s, 2009 (suppl; abstr 1022) 2009. 
29. Baselga J, Gelmon KA, Verma S, et al. Phase II trial of pertuzumab and trastuzumab 
in patients with human epidermal growth factor receptor 2-positive metastatic breast 
cancer that progressed during prior trastuzumab therapy. J Clin Oncol. 
2010;28(7):1138-1144. 
30. Gianni L, Pienkowski T, Im Y-H, et al. Neoadjuvant Pertuzumab (P) and 
Trastuzumab (H): Antitumor and Safety Analysis of a Randomized Phase II Study 
('NeoSphere'). Presented at the San Antonio Breast Cancer Symposium 2010. 
(Abstract S3-2). 2010. 
31. Baselga J, Cortes J, Kim SB, et al. Pertuzumab plus Trastuzumab plus Docetaxel for 
Metastatic Breast Cancer. NEJM 366(2):109-19, 2012. 
32. Swain SM, Kim SB, Cortes J, et al. Pertuzumab, trastuzumab, and docetaxel for 
HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results 
from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 
2013;14(6):461-471. 
33. Gianni L, Pienkowski T, Im YH, et al. Efficacy and safety of neoadjuvant pertuzumab 
and trastuzumab in women with locally advanced, inflammatory, or early HER2-
positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 
trial. Lancet Oncol 13(1); 25-31, 2012. 
34. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search
.Label_ApprovalHistory.   
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.Label ApprovalHistory. 
35. Hurwitz D, Hainsworth JD, Swanton C, et al. Targeted therapy for gastrointestinaI 
(GI) tumors based on molecular profiles: Early results from MyPathway, an open-
label phase IIa basket study in patients with advanced solid tumors. J Clin Oncol 34, 
2016 (suppl 4S; abstr 653)  
36. Siena S, Sartore-Bianchi A, Trusolino L, et al. CT005 – Final results of the 
HERACLES trial in HER2-amplified colorectal cancer. 
http://www.abstractsonline.com/pp8/#!/4292/presentation/12323. 
 
 
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Molecular Analysis for Therapy Choice (MATCH) 
MATCH Treatment Subprotocol J: HP in HER2 Amplification 
Appendix I 
 
Actionable Mutations for Sub-Protocol EAY131-J 
 
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content. 
 
Rev. Add25 
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Molecular Analysis for Therapy Choice (MATCH) 
MATCH Treatment Subprotocol J: HP in HER2 Amplification 
Appendix II 
 
Patient Drug Information Handout and Wallet Card 
Information for Patients, Their Caregivers and Non-Study Healthcare Team on Possible 
Interactions with Other Drugs and Herbal Supplements 
The patient ____________________________ is enrolled on a clinical trial using the 
experimental study drugs, Trastuzumab and Pertuzumab. This clinical trial is sponsored by the 
National Cancer Institute. This form is addressed to the patient, but includes important 
information for others who care for this patient. 
There are no expected interactions with other medications. 
To the patient: Take this paper with you to your medical appointments and keep the 
attached information card in your wallet. 
There are no expected interactions with other medications. 
However, it is still important to tell your study doctors of any medicines you are taking before 
you enroll onto this clinical trial.  It is also very important to tell your doctors if you stop taking 
any regular medicines, or if you start taking a new medicine while you take part in this study.  
When you talk about your current medications with your doctors, include medicine you buy 
without a prescription (over-the-counter remedy), or any herbal supplements such as St. John’s 
Wort.  It is helpful to bring your medication bottles or an updated medication list with you. 
Many health care providers can write prescriptions. You must tell all of your health care 
providers (doctors, physician assistants, nurse practitioners, pharmacists) you are taking part in 
a clinical trial. 
These are the things that you and they need to know: 
x 
Your regular health care provider should call your study doctor before prescribing any new 
medicine or discontinuing any medicine. 
Your study doctor’s name is 
_____________________________________ 
and he or she can be contacted at: 
_____________________________________.
Use of this document is governed by the terms of use on the first page of this document.

ECOG-ACRIN 
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Cancer Research Group 
Version Date: November 10, 2022 
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¾ Before you enroll onto the clinical trial, your 
study doctor will work with your regular health 
care providers to review any medicines and 
herbal supplements that should be 
discontinued. 
¾ Before prescribing new medicines, your 
regular health care providers should contact 
your study doctor. 
¾ Your study doctor’s name is 
_____________________________ and can 
be contacted at 
_________________________________.  
STUDY DRUG INFORMATION WALLET CARD 
You are enrolled on a clinical trial using the 
experimental study drugs Trastuzumab and 
Pertuzumab.  This clinical trial is sponsored by the 
NCI.  There are no expected interactions with 
other medications.  However, it is still important 
to: 
¾ Tell your doctors if you stop taking any 
medicines or if you start taking any new 
medicines. 
¾ Tell all of your health care providers (doctors, 
physician assistants, nurse practitioners, or 
pharmacists) that you are taking part in a clinical 
trial. 
¾ Check with your doctor or pharmacist whenever 
you need to use an over-the-counter medicine or 
herbal supplement. 
Use of this document is governed by the terms of use on the first page of this document.