MATCH Treatment Subprotocol Y: AZD5363 in Patients With Tumors With AKT Mutations
Phase: PHASE2
Conditions: Advanced Lymphoma, Advanced Malignant Solid Neoplasm, Hematopoietic and Lymphoid Cell Neoplasm, Refractory Lymphoma, Refractory Malignant Solid Neoplasm, Refractory Multiple Myeloma
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 
 
 
 
July 10, 2019 
 
Martha Kruhm, MS RAC 
Head, Protocol and Information Office 
Quality Assurance Section 
CTEP, DCT, NCI 
6130 Executive Blvd, EPN Room 7000 
Bethesda, MD   20892 
Dear Ms. Kruhm: 
Enclosed is Addendum #21 to EAY131-Y, AZD5363 in Patients with Tumors with AKT 
Mutations. 
Please replace your current copy of the protocol and Informed Consent document (if ICD 
changed) with this (these) updated version(s).  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. 
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permitted to conduct the study utilizing outdated versions of any MATCH protocol documents 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 Dr. L. Austin Doyle March 29, 2019 Request for Amendment 
for AZD5363. 
The following revisions to EAY131-Y protocol have been made in this addendum: 
 
Section 
Change 
1. 
Cover Page  
Update Version date 
2. 
3.3 
Updated the AZD5363 CAEPR list with version 2.3, February 28, 2019 
The following revisions to EAY131-Y Informed Consent Document have been made in this 
addendum: 
 
Section 
Change 
1. 
Page 1 
Updated Version Date 
2. 
What possible risks can 
I expect from taking 
part in this study? 
Updated the AZD5363 possible risks risk list with version 2.3 February 
28, 2019. 
If you have any questions regarding this addendum, please contact aagu@ecog-acrin.org or 
857-504-2900. 
We request review and approval of this addendum to EAY131-Y so ECOG-ACRIN may activate 
it promptly.   

ii 
Thank you.  
Sincerely, 
Pamela Cogliano 
Protocol Development Manager 
Enclosure 
CC: Kevin Kalinsky, MD, MS  
Carolyn McCourt  .MD 
Jasgit Sachdev, M.D  
Alice Chen, MD 
Keith Thomas Flaherty, MD 
Lyndsay N. Harris. MD 
Peter O’Dwyer, MD 
Mickey Williams, PhD 
James V. Tricoli, PhD 
Stanley Hamilton, MD 
Lisa McShane, PhD  
Larry Rubinstein, PhD 
Robert Gray, PhD 
Shuli Li, PhD 
Lalitha Shankar, MD 
Susanna Lee, MD, PhD 
Constantine Gastonis, PhD 
Paolo Caimi, MD 
Shaji Kumar, MD 
Carlos Arteaga, MD 
Edith Mitchell, MD 
John J. Wright, MD, PhD 
Bruce Giantonio, MD 
Donna Marinucci 
Kerry Higgins 
Gayle Ipock 
Jean MacDonald 
Carol Chami, R.N. 
Juanita Andrews 
Melinda Flood 
Julianne Human 
Kelly Redmond 
Becky Fillingham 
Jeffrey Zhang 
Amy Li 
Kevin Pollard 
Abuchi Agu 
Michael T. Balco 
Lauren Lambert 
Cayden Maican 
Margaret Cavenagh 
Ben Kim 
Alexandra Sachs 
Russell McDaniel  
Elanna Radomyshelsky 
 
 

EAY131-Y 
1 
Molecular Analysis for Therapy Choice (MATCH) 
MATCH Treatment Subprotocol Y: AZD5363 in Patients 
with Tumors with AKT Mutations 
AZD5363 TREATMENT SUBPROTOCOL CHAIR: Kevin Kalinsky, M.D., M.S. 
AZD5363 TREATMENT SUBPROTOCOL CO-
CHAIR: 
Carolyn McCourt, M.D. 
AZD5363 TRANSLATIONAL CHAIR: Jasgit Sachdev, M.D. 
Version Date:  July 10, 2019 
NOTE: This subprotocol (EAY131-Y) should 
be used in conjunction with the 
MATCH Master Protocol (EAY131).  
NOTE: As of 11/17, all protocol changes will 
be noted by addendum number. 
Please reference the activation memo 
for the addendum activation date. 
SUBPROTOCOL ACTIVATION DATE 
May 31, 2016 (incorporated in Addendum #3) 
Addendum #4 – 7/16 
Addendum #5 – 12/16 
Addendum #7 – 3/17 
Addendum #11 – 8/17 
Addendum #13 
Addendum #21 
Agent 
IND# 
NSC# 
Supply 
AZD5363 
IND Sponsor: DCTD, NCI IND#:  
782347 
NCI Supplied 
Rev. Add13 

ECOG-ACRIN 
EAY131-Y 
Cancer Research Group 
Version Date: July 10, 2019 
2 
Table of Contents 
Molecular Analysis for Therapy Choice (MATCH) .................................................. i 
MATCH Treatment Subprotocol Y: AZD5363 in Patients with Tumors with AKT 
Mutations ................................................................................................... 1 
Table of Contents .............................................................................................. 2 
Schema ............................................................................................................. 4 
1. Introduction ................................................................................................ 5 
1.1 
AZD5363 ............................................................................................ 5 
1.2 
Supporting Preliminary Data ............................................................... 7 
2. Selection of Patients .................................................................................. 11 
2.1 
Eligibility Criteria .............................................................................. 11 
3. AZD5363 Treatment Plan ........................................................................... 13 
3.1 
Administration Schedule ................................................................... 13 
3.2 
Adverse Event Reporting Requirements ............................................. 14 
3.3 
Comprehensive Adverse Events and Potential Risks list (CAEPR) for 
AZD5363 (NSC 782347) ..................................................................... 16 
3.4 
Dose Modifications ........................................................................... 19 
3.5 
Supportive Care ................................................................................ 22 
3.6 
Duration of Agent-specific treatment................................................. 22 
3.7 
Duration of Follow-Up ...................................................................... 23 
4. Study Parameters ...................................................................................... 24 
4.1 
Therapeutic Parameters for AZD5363 Treatment................................ 24 
5. Drug Formulation and Procurement ........................................................... 27 
5.1 
AZD5363 (NSC 782347) ..................................................................... 28 
6. Translational Studies.................................................................................. 31 
7. References ................................................................................................ 31 
Appendix I  Patient Pill Calendar ....................................................................... 33 
Appendix II  Actionable Mutations for Sub-Protocol EAY131-Y ............................ 36 
Appendix III  CYP3A4 Strong Inducers and Potent Inhibitors ............................... 42 
Appendix IV  PI3K/AKT inhibitors in development .............................................. 43 
Appendix V  Information On Possible Drug Interactions ..................................... 45 
 
 
 

ECOG-ACRIN 
EAY131-Y 
Cancer Research Group 
Version Date: July 10, 2019 
3 
TREATMENT SUBPROTOCOL CHAIR 
Kevin Kalinsky, MD MS 
Columbia University Medical Center 
Herbert Irving Pavilion 
161 Fort Washington, Room 1069 
New York, New York 10032 
Phone: 212-305-1945 
Fax: 212-305-0178 
Email: kk2693@cumc.columbia.edu 
 
 
 
TREATMENT SUBPROTOCOL CO-CHAIR  
Carolyn McCourt, MD 
Washington University School of Medicine 
Department of Obstetrics and Gynecology 
Campus Box 8064, 660 S. Euclid Ave. 
St. Louis, Missouri 63110 
Phone: 314-996-6000 
Fax: 314-996-6060 
Email: mccourtc@wudosis.wustl.edu 
 
 
TRANSLATIONAL CHAIR 
Jasgit Sachdev, MD 
HonorHealth Research Institute 
10510 North 92nd Street, 2nd Floor 
Scottsdale, Arizona 85258 
Phone: 480-323-1350 
Fax: 480-323-1359 
Email: Jasgit.sachdev@honorhealth.com 
 
 
 
 

ECOG-ACRIN 
EAY131-Y 
Cancer Research Group 
Version Date: July 10, 2019 
4 
Schema 
 
Long-Term Follow-Up
AZD5363 480 mg PO twice a 
day, 4 days on/3 days off on a 
weekly basis for each 28 day 
cycle1
Until Progression or 
unacceptable toxicity
Cycle = 28 days
Accrual Goal: 35
1. If patient has Hormone Receptor positive, Her2 negative metastatic breast cancer with demonstration of progression on an 
aromatase inhibitor or fulvestrant, (s)he can continue the aromatase inhibitor or fulvestrant that was just being administered in 
addition to AZD5363.  Patients continuing hormone therapy will start with AZD5363 dosing of 400 mg PO twice a day 4 days on/3 
days off on a weekly basis for each 28 day cycle.
 
 

ECOG-ACRIN 
EAY131-Y 
Cancer Research Group 
Version Date: July 10, 2019 
5 
1. Introduction 
1.1 
AZD5363 
AZD5363 is a potent, pan-AKT inhibitor of the kinase activity of AKT. In vitro, 
AZD5363 inhibits all 3 isoforms of AKT, with an IC50 < 10nmol/L AKT (IC50of 
AKT1, AKT2 and AKT3 of 3, 7 and 7nM respectively)1. In vivo, AZD5363 activity 
has been demonstrated with inhibition of phosphorylation of the substrates 
PRAS40, GSK3B, and S6 by 80-90%. The presence of abnormalities in the 
PI3K/AKT pathway in cell lines, including PIK3CA mutations or PTEN loss or 
inactivating mutation, correlates with sensitivity to AZD53631,2. Tumor volume 
decrease has been shown in various xenograft models in immunodeficient mice, 
including BT474c model (PIK3CA mutant, HER2+ breast cancer), HCC-1952 
(PIK3CA mutant, HER2+ breast cancer), 786-0 (PTEN null, VHL null renal cell 
carcinoma), and HGC27 (PIK3CA mutant, PTEN mutant gastric cancer)1. In 
unpublished data, AZD5363 reverses expression of AKT1 E17K-induced colony 
formation in mammary epithelial cells (Astra-Zeneca, confidential). In 
unpublished data, AZD5363 has also demonstrated tumor volume reduction in 2 
AKT1 E17K mutant breast cancer explant models [confidential: IB (Investigator’s 
Brochure)].  In human breast cancer (HBC)-x31 explants, mean tumor volume 
decreased by 89% (p < 0.001 compared to controls) (IB, confidential). The 
tumors in 6 out of 8 mice in the group showed almost complete regression to  
< 20 mm3 (IB, confidential). In HBC-x2 explants, AZD5363 inhibited mean tumor 
volume by 76% compared to controls (p < 0.001) (IB, confidential). 
There are no FDA approved AKT inhibitors for cancer treatment.  AZD5363 is 
currently under investigation in phase I and II trials (www.clinicaltrials.gov). It is 
not FDA approved for any indication.  At ASCO 2015, data from a phase I trial in 
patients with PIK3CA mutated breast and gynecologic cancers was presented3.In 
this adaptive design, continuous dosing vs. intermittent dosing (4 days on/3 days 
off vs. 2 days on/5 days off) was being assessed3. In this study, 47, 21 and 22 
patients were treated on the continuous dosing [Maximum Tolerated Dose (MTD: 
320 mg BID], 4/3 (480 mg BID) and 2/5 schedules (640 mg BID). Dose limiting 
toxicities (DLTs) were rash and diarrhea for continuous dosing, and 
hyperglycemia for 2/5. No DLTs were identified for the 4/3 schedule. The most 
common causally-related grade 3 or greater adverse events were as follows: 
hyperglycemia (20%), diarrhea (10%), rash (10%), nausea (3%) and fatigue 
(1%). In accordance, the most common adverse events identified in the IB are 
diarrhea, hyperglycemia, and hypersensitivity (confidential).  As proof of 
mechanism, reduction in the substrates pGSK3β and pPRAS40 was 
demonstrated in platelet-rich plasma3. Target lesion shrinkage was observed in 
7/15 and 4/14 patients in the breast and gynecologic cohorts respectively to date. 
In PIK3CA mutant breast cancer as a single agent, 2 patients had a partial 
response (both helical domain PIK3CA mutations, no PTEN loss).  There was 
also 1 patient with gynecological cancer with a partial response (approximately 
50% reduction in sum of target diameter), with a mutation in the p85 adaptor 
binding domain and PTEN null.  Patients with PIK3CA mutations are potentailly 
eligible for protocol I of the NCI Match. Based on the data above, the 
recommended phase II dose is 480 mg BID, given as 4 days on/3 days off on a 
weekly basis. 

ECOG-ACRIN 
EAY131-Y 
Cancer Research Group 
Version Date: July 10, 2019 
6 
There is clinical evidence of anti-cancer activity with AZD5363 in patients with 
AKT mutated tumors.  At the 2015 AACR-NCI-EORTC International Conference 
on Molecular Targets and Cancer Therapeutics4, data were presented on 
patients with tumors harboring AKT1 mutations who received 480 mg BID, 4 
days on/3 days off. Of the 18 patients with estrogen receptor (ER) + metastatic 
breast cancer, 14 patients demonstrated target lesion shrinkage, with 3 patients 
having a confirmed partial response and 2 patients with unconfirmed partial 
responses. Of those with confirmed responses, one patient was on study for 14.3 
months prior to progression and one remains on study (3.7 months). In patients 
with gynecologic tumors, 9 out of 11 patients demonstrated target lesion 
shrinkage, with 3 patients having confirmed partial responses. One of these 
patients with endometroid carcinoma of the ovary has been on-study for 39.2 
months, with an ongoing partial response. In those with other advanced AKT1 
mutant solid tumors, 10 of 12 patients demonstrated target lesion shrinkage, with 
1 patient with a metastatic adenocarcinoma of unknown primarily demonstrating 
a confirmed partial response. These data suggest that AKT inhibition with 
AZD5363 may provide a novel therapeutic approach and serve as the rationale 
for investigating this agent in AKT mutated tumors. 
In addition, there is recent data that the combination of AZD5363 with endocrine 
therapy is superior to monotherapy in ER+ breast cancer in endocrine sensitive 
and endocrine-resistant cell lines5. The combination of AZD5363 with endocrine 
therapy results in a dose-dependent decrease in proliferation in the majority of 
ER + breast cancer cell lines adapted to LTED (long-term estrogen deprivation) 
or tamoxifen resistance, including MCF7, HCC1228, T47D, ZR75.1. Thus, the 
combination leads to a re-sensitization of endocrine-resistant tumors. For 
instance, AZD5363 re-sensitizes TAM-resistant cells to tamoxifen and acts 
synergistically with fulvestrant. Treatment with AZD5363 results in a significant 
reduction of notable PI3K/AKT pathway downstream effectors, such as pPRAS40 
and S6 kinase. In a patient-derived luminal breast cancer xenograft 
HBCx22OvaR with acquired resistance to estrogen deprivation, combination of 
fulvestrant with AZD5363 causes an almost complete inhibition of tumor grown 
(80% inhibition). Importantly, the combination is significantly more active than 
AZD5363 and fulvestrant monotherapy groups (p= 3.75E-03 and 6.3E-04, 
respectively: Fig 1A).  After 90 days of treatment, therapies were withdrawn and 
tumor volume assessed for efficacy. Removal of AZD5363 leads to a rise in 
tumor volume within 10 days after withdrawal (Fig 1B). The combination of 
AZD5363 shows a sustained antitumor effect after 50 days of treatment 
cessation (Fig 1C). 

ECOG-ACRIN 
EAY131-Y 
Cancer Research Group 
Version Date: July 10, 2019 
7 
 
At the 2015 AACR-NCI-EORTC International Conference on Molecular Targets 
and Cancer Therapeutics, a heavily pre-treated patient (10 prior lines) with an 
AKT1 E17K and ESR D538G mutant ER+ breast cancer was presented4. She 
had previously progressed on fulvestrant as well as AZD5363 monotherapy. 
When fulvestrant was added to AZD5363 on day 121 of AZD5363 treatment, 
follow-up scans showed shrinkage of her primary breast tumor and resolution of 
liver metastasis. These studies demonstrate that the combination of AZD5363 
with hormone therapy may delay or overcome resistance to AZD5363 
monotherapy in hormone receptor positive metastatic breast cancer. 
1.2 
Supporting Preliminary Data  
The PI3K-AKT pathway is one of the most commonly altered pathways in cancer, 
including mutations, somatic copy number abnormalities, increased expression, 
and aberrant signaling6. A number of intrinsic and extrinsic survival signals 
induced by several receptors are thought to be transduced downstream through 
the PI3K/AKT pathway. In addition, hyperactivity of this pathway promotes 
resistance to pro-apoptotic signaling induced by chemotherapy and other anti-
neoplastic therapies. 
Fig 1: The 
combination of 
fulvestrant with 
AZD5363 is better 
than monotherapy 
in a hormone 
refractory model 
(A). Long-term 
study changes in 
tumor volume after 
withdrawal of 
AZD5363 (B) or the 
combination (C). 

ECOG-ACRIN 
EAY131-Y 
Cancer Research Group 
Version Date: July 10, 2019 
8 
Overview of PI3K-AKT pathway: 
The PI3K-AKT pathway can be activated upstream by a wide variety of receptor 
protein tyrosine kinases (RTKs; in particular growth factor receptors), cytokine 
receptors, intracellular tyrosine kinases, G-protein coupled receptors, and 
intracellular small GTPases such as Ras6. In the case of RTKs, activation by 
ligand binding results in the non-covalent association of phosphatidylinositol-3 
kinases (PI3Ks) with phosphotyrosine consensus motifs on the intracellular 
domain of the RTK7.  One or two src-homology 2 (SH2) domains on the beta 
(regulatory) subunit of PI3K participate in this interaction, which results in 
allosteric changes to the catalytic alpha subunit of PI3K, leading to functional 
activation. The phosphatidylinositol 3,4,5-trisphosphate (PIP3) is generated as a 
result of phosphorylation by activated PI3K, and resides on the inner side of the 
plasma membrane. PIP3 is then able to activate a number of proteins, including 
PDK1, AKT, and other serine/threonine kinases.  The pleckstrin homology 
domain of AKT interacts with PIP3, resulting in transient localization of AKT to 
the inner membrane and subsequent phosphorylation of the Thr308 and Ser473 
residues by phosphoinositide-dependent kinases 1 and 2 (PDK1, PDK2), 
respectively. PDK1 itself is activated by PIP3, while PDK2 has been recently 
identified as mTORC2 (the complex rictor/mTOR)8. Phosphorylated AKT (p-AKT) 
represents the active form. The tumor suppressor phosphatase and tensin 
homologue deleted on chromosome 10 (PTEN) is an important negative 
regulator of the PI3K/AKT pathway, as it functions to rapidly convert PIP3 back to 
PIP29. 
Activation of AKT regulates multiple cellular processes including cell survival, cell 
proliferation, cell growth, and various aspects of cellular metabolism. AKT 
(Protein Kinase B) is an evolutionarily conserved serine threonine kinase with 3 
forms in mammalian species, AKT1, AKT2, and AKT3, all encoded by different 
genes9. AKT represents an important signaling hub with well over 100 
downstream target proteins that it is able to activate or inactivate through 
phosphorylation of serine and threonine residues. AKT modulates cell survival, 
cell cycle progression, and cellular growth through phosphorylation of these 
downstream targets, including inhibition of Bad and caspase 9, phosphorylation 
of Mdm2 leading to p53 ubiquitination, and phosphorylation of mTOR, 
respectively10. Although the subset of downstream AKT effectors that are most 
crucial for tumor development have not been entirely elucidated, there is 
substantial evidence that mammalian target of rapamycin complex 1 (mTORC1) 
plays an important role. AKT activates mTORC1 by several mechanisms 
including phosphorylation and inhibition of the tumor suppressor tuberous 
sclerosis complex 2 (TSC2) that binds to and negatively regulates mTORC1 
activity (Fig 2)11. 

ECOG-ACRIN 
EAY131-Y 
Cancer Research Group 
Version Date: July 10, 2019 
9 
 
Alterations to the PI3K-AKT pathway in cancer: 
Mutations in genes encoding for the subunits of PI3K represent some of the most 
commonly mutated genes in all of cancer, with kinase domain activating point 
mutations in the PIK3CA gene (which encodes for p110α), second only to p53 as 
the most commonly occurring mutations in all tumor specimens in The Cancer 
Genome Atlas (TCGA)12. PTEN loss of function mutations, silencing by 
methylation and other epigenetic changes, and large scale chromosomal 
changes leading to loss of PTEN are also amongst the more common 
aberrations seen across many different cancer types, and in particular in 
metastatic cancer. Germline mutations in PTEN are responsible for the Cowden 
familial cancer syndrome. Mutations in PTEN and PIK3CA do not appear to be 
mutually exclusive, underscoring the complex functioning of the various 
components of the PI3K-AKT pathway13. 
On the other hand, mutations in AKT genes are rarely found in human cancers to 
date13. Activating mutations have been described in a small percentage of breast 
cancers, head and neck squamous cell carcinomas, endometrial cancer, non-
small cell lung cancer, and renal cancers14.  An AKT1 point mutation in the 
pleckstrin homology domain that replaces a glutamic acid with lysine (E17K) at 
residue 17 is the most commonly reported mutation, and is thought to confer 
increased activity by promoting its localization to the plasma membrane14. AKT 
E17K mutation, for example, is seen in 2-3% of breast cancer, and other AKT 
mutations have been seen in this tumor as well (BROAD, SANGER, TCGA). 
AKT1 mutations were seen in luminal A, B and the HER2 subset, but not in basal 
type. Other activating mutations reported in the literature include the E49K 
(AKT1) and G171R substitutions (AKT3), which occur in the pleckstrin homology 
Fig 2: The 
PI3K/AKT 
pathway. The 
role of AKT and 
downstream 
effectors are 
demonstrated. 

ECOG-ACRIN 
EAY131-Y 
Cancer Research Group 
Version Date: July 10, 2019 
10 
domain and in the kinase domain, respectively. Measurement of p-AKT levels in 
both tumors and cancer cell lines confirms a quantitative increase in activated 
AKT as a consequence of these point mutations, and overall levels of p-AKT 
appear to correlate with sensitivity to AKT inhibition14. 
In addition to mutations, there are other means of augmenting AKT activity, 
including AKT gene amplification and AKT rearrangements. However, there is no 
evidence of pre-clinical or clinical benefit of an AKT inhibitor, such as AZD5363, 
with AKT amplifications or fusions16-18. To date there is no approved targeted 
treatment for patients with AKT mutations; this trial may produce clinical 
validation data that such patients can respond to an AKT inhibitor. 

ECOG-ACRIN 
EAY131-Y 
Cancer Research Group 
Version Date: July 10, 2019 
11 
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 
Eligibility Criteria 
2.1.1 
Patients must fulfill all eligibility criteria outlined in Section 3.1 of 
MATCH Master Protocol (excluding Section 3.1.6) at the time of 
registration to treatment step (Step 1, 3, 5, 7). 
2.1.2 
Patients must have an AKT mutation as determined via the MATCH 
Master Protocol. See Appendix II for a list of the AKT mutation and 
corresponding Levels of Evidence. 
2.1.3 
Patients with hormone receptor positive, defined as estrogen receptor 
and/or progesterone receptor > 1% by immunohistochemistry19, AND 
HER2 negative unresectable breast cancer, with no overexpression 
by IHC or amplification by in-situ hybridization20, are allowed to 
continue fulvestrant or an aromatase inhibitor (anastrazole, letrozole, 
exemestane) with AZD5363 if patient just progressed on this anti-
estrogen therapy. GnRH agonists (such as leuprolide or goserelin) are 
allowed. For instance, if the last treatment was letrozole plus 
goserelin, the patient is allowed to continue the letrozole plus 
goserelin with AZD5363. 
NOTE: 
SERMs, such as tamoxifen or toremifene, are not allowed, 
given concerns about CYPD26 and CYP3A4 metabolism, 
respectively. 
_____
_____
_____
Rev. Add13 

ECOG-ACRIN 
EAY131-Y 
Cancer Research Group 
Version Date: July 10, 2019 
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2.1.4 
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:  _______________ 
2.1.5 
Patients must not have known hypersensitivity to AZD5363 or 
compounds of similar chemical or biologic composition. 
2.1.6 
Patients with known KRAS, NRAS, HRAS, or BRAF mutations are not 
eligible for this protocol, as these mutations may lead to limited 
response due to resistance. 
2.1.7 
Patients with diabetes or risk for hyperglycemia are eligible.  Patients 
with diabetes mellitus may enter the study unless any of the following 
exclusion criteria are fulfilled: 
- Baseline fasting glucose value of >8.9 mmol/L or 160 mg/dL  
(fasting is defined as no calorific intake for at least 8 hours) 
- Insulin required for routine diabetic management and control 
- More than two oral hypoglycemic medications required for routine 
diabetic management and control 
2.1.8 
Patients may not have received treatment with another inhibitor of 
PI3K, AKT or mTOR in the neoadjuvant, adjuvant or metastatic setting 
with the exception of FDA approved rapalogs. Patients with metastatic 
cancer, who received PI3K/AKT/mTOR inhibitors on short 
preoperative window trials (treatment for 4 weeks or less) will be 
eligible if the treatment was over 6 months prior to registration (See 
Appendix IV). 
2.1.9 
Patients may not have received strong inhibitors or potent inducers or 
substrates of CYP3A4 or substrates of CYP2D6 within 2 weeks before 
the first dose of study treatment (3 weeks for St John’s Wort). See 
Section 5.1.8 and Appendix III. 
 
 
 
 
 
Physician Signature 
 
Date 
OPTIONAL: 
This signature line is provided for use by institutions wishing to 
use the eligibility checklist as source documentation. 
 
 
_____
_____
_____
_____ 
_____
_____ 

ECOG-ACRIN 
EAY131-Y 
Cancer Research Group 
Version Date: July 10, 2019 
13 
3. 
AZD5363 Treatment Plan 
3.1 
Administration Schedule 
Patients will be instructed to take AZD5363 480 mg orally twice daily, 4 days on/3 
days off on a weekly basis for each 28 day cycle, until tumor progression or 
unless patient experiences unacceptable toxicities. Cycles are defined in 28-day 
periods to facilitate scheduling of visits and assessments. 
NOTE:  
Twice daily doses should be taken at approximately the same time 
each morning and evening approximately 12 hours apart.   
NOTE:  
AZD5363 should be taken with water only on an empty stomach, no 
food for 2 hours prior to dose and for 1 hour after dose. 
In the event that a patient vomits after AZD5363 dosing, the patient must not 
retake new capsule(s)/tablet(s), but continue to take the next dose 12 hours later. 
Should a patient miss a scheduled dose, the patient will be allowed to take the 
dose up to a maximum of 2 hours after the scheduled dose time. If greater than 2 
hours after the scheduled dose time, the missed dose should not be taken and 
the patient should take their allotted dose at the next scheduled time. If a patient 
needs to take the dose earlier for whatever reason, the patient can take the dose 
up to 2 hours earlier than the scheduled dose time. The patient should make 
every reasonable effort to take the AZD5363 capsule(s) / tablets(s) on time. 
If the patient has HR positive/HER2 negative unresectable breast cancer, (s)he is 
allowed to continue fulvestrant or an aromatase inhibitor (anastrazole, letrozole, 
exemestane) with AZD5363 if s(he) most recently progressed on this anti-
estrogen therapy. For instance, if the last treatment was fulvestrant, the patient is 
allowed to continue the fulvestrant in combination with AZD5363. SERMs, such 
as tamoxifen or toremifene, are not allowed. 
NOTE: 
Patients who will be continuing fulvestrant or an aromatase inhibitor 
will be instructed to take AZD5363 400 mg orally daily twice a day, 4 
days on/3 days off on a weekly basis for each 28 day cycle, until 
tumor progression or unless patient experiences unacceptable 
toxicities. This is based upon the recommended phase II dosing 
performed in the phase I trials with AZD5363. 
Fulvestrant will be administered 500 mg intramuscularly into the buttocks slowly 
(1 to 2 minutes per injection) as two 250-mg injections, one in each buttock every 
28 days (+/- 7 days). As the patients will have just progressed on fulvestrant, re-
loading will not be necessary, and patients can continue on the 28 day schedule. 
Fulvestrant will be given as standard of care and not supplied by the study. 
An aromatase inhibitor (anastrazole 1 mg, letrozole 2.5 mg, or exemestane 25 
mg) is allowed to continue, if the patient most recently progressed on this agent. 
For instance, if s(he) just progressed on anastrozole, anastrazole can continue in 
combination with AZD5363. If the patient previously was receiving a GnRH 
agonist (such as leuprolide or goserelin), this should continue as previously 
administered. Aromatase inhibitors and GnRH agonists will be given as standard 
of care and not supplied by the study. 
Rev. 3/17 

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If the patient most recently progressed on the combination of fulvestrant plus an 
aromatase inhibitor, both may agents may continue in combination with 
AZD5363. 
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 Y 
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 Y specific expedited reporting 
requirements: 
• 
Pregnancies:  Pregnancies and suspected pregnancies 
(including a positive or inconclusive pregnancy test, regardless 
of age or disease state) occurring while the subject is on 
AZD5363, or within 28 days of the subject’s last dose of 
AZD5363, 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. 
 
EAY131 – Subprotocol Y specific expedited reporting 
exceptions: 
For Subprotocol Y, the adverse events listed below do not require 
expedited reporting via CTEP-AERS: 
• 
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.  

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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 
• 
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. 
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. 
• 
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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3.3 
Comprehensive Adverse Events and Potential Risks list (CAEPR) for AZD5363 
(NSC 782347) 
The Comprehensive Adverse Events and Potential Risks list (CAEPR) provides a 
single list of reported and/or potential adverse events (AE) associated with an 
agent using a uniform presentation of events by body system. In addition to the 
comprehensive list, a subset, the Specific Protocol Exceptions to Expedited 
Reporting (SPEER), appears in a separate column and is identified with bold and 
italicized text. This subset of AEs (SPEER) is a list of events that are protocol 
specific exceptions to expedited reporting to NCI (except as noted below).  Refer 
to the 'CTEP, NCI Guidelines: Adverse Event Reporting Requirements' 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/aeguide
lines.pdf  for further clarification. Frequency is provided based on 297 patients. 
Below is the CAEPR for AZD5363. 
NOTE: 
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 in the SPEER. 
Version 2.3, February 28, 20191 
 
Adverse Events with Possible 
Relationship to AZD5363 
(CTCAE 5.0 Term) 
[n= 297] 
 
 
 
Specific Protocol 
Exceptions to Expedited 
Reporting (SPEER) 
 
Likely (>20%) 
Less Likely (<=20%) 
Rare but Serious (<3%) 
 
BLOOD AND LYMPHATIC SYSTEM DISORDERS 
 
Anemia 
 Anemia (Gr 2) 
GASTROINTESTINAL DISORDERS 
 
Abdominal pain 
 Abdominal pain (Gr 2) 
Constipation 
 Constipation (Gr 2) 
Diarrhea 
 
 Diarrhea (Gr 2) 
Mucositis oral 
 Mucositis oral (Gr 2) 
Nausea 
 
 Nausea (Gr 2) 
Vomiting 
 
 Vomiting (Gr 2) 
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS 
 
Edema limbs 
 
Fatigue 
 
 Fatigue (Gr 2) 
Fever 
 
 Fever (Gr 2) 
IMMUNE SYSTEM DISORDERS 
 
 
Allergic reaction 
 
INVESTIGATIONS 
 
Creatinine increased 
 Creatinine increased (Gr 2) 
Weight loss 
 
METABOLISM AND NUTRITION DISORDERS 
 
Anorexia 
 
 Anorexia (Gr 2) 
Hyperglycemia 
 
 Hyperglycemia (Gr 2) 
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS 
 
Back pain 
 
NERVOUS SYSTEM DISORDERS 
 
Dizziness 
 
Headache 
 Headache (Gr 2) 
Rev. 8/17 
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Adverse Events with Possible 
Relationship to AZD5363 
(CTCAE 5.0 Term) 
[n= 297] 
 
 
 
Specific Protocol 
Exceptions to Expedited 
Reporting (SPEER) 
 
Likely (>20%) 
Less Likely (<=20%) 
Rare but Serious (<3%) 
 
RENAL AND URINARY DISORDERS 
 
Proteinuria 
 Proteinuria (Gr 2) 
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS 
 
Cough 
 
Dyspnea 
 
SKIN AND SUBCUTANEOUS TISSUE DISORDERS 
 
Dry skin 
 Dry skin (Gr 2) 
Pruritus 
 
Skin and 
subcutaneous tissue 
disorders - Other 
(rash)2  
 
 
Skin and subcutaneous 
tissue disorders - Other 
(rash)2 (Gr 2) 
1 This table will be updated as the toxicity profile of the agent is revised.  Updates will be distributed to all 
Principal Investigators at the time of revision.  The current version can be obtained by contacting 
PIO@CTEP.NCI.NIH.GOV.  Your name, the name of the investigator, the protocol and the agent should 
be included in the e-mail. 
2 Rash may include dry skin, skin fissures, xeroderma, dermatitis exfoliative, exfoliative rash, eyelid 
exfoliation, skin exfoliation, xerosis, rashes and acnes, rash, rash generalized, rash macular, rash 
maculo-papular, rash maculovesicular, rash morbilliform, rash vesicular, rash follicular, acne pustular, 
rash pustular, folliculitis, eyelid folliculitis, acne, dermatitis acneiform, drug eruption pruritus, eyelids 
pruritus, pruritus generalized, erythema, and erythematous rash. 
Adverse events reported on AZD5363 trials, but for which there is insufficient evidence to 
suggest that there was a reasonable possibility that AZD5363 caused the adverse event: 
CARDIAC DISORDERS - Heart failure 
GASTROINTESTINAL DISORDERS - Esophageal pain; Gastrointestinal disorders - Other 
(intestinal obstruction); Small intestinal obstruction 
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS - Malaise 
INFECTIONS AND INFESTATIONS - Lung infection; Sepsis; Skin infection; Urinary tract 
infection 
INVESTIGATIONS - Alanine aminotransferase increased; Alkaline phosphatase increased; 
Aspartate aminotransferase increased; Blood bilirubin increased; Neutrophil count decreased; 
White blood cell decreased 
METABOLISM AND NUTRITION DISORDERS - Dehydration; Glucose intolerance; 
Hypercalcemia; Hypokalemia; Hypomagnesemia; Hyponatremia; Hypophosphatemia 
NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS) - 
Tumor pain 
NERVOUS SYSTEM DISORDERS - Neuralgia 
PSYCHIATRIC DISORDERS - Confusion 
RENAL AND URINARY DISORDERS - Acute kidney injury 
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS - Oropharyngeal pain; Pleural 
effusion; Productive cough 
VASCULAR DISORDERS - Thromboembolic event 

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NOTE: 
AZD5363 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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3.4 
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). 
Patients will be monitored closely for toxicity and the dose of AZD5363 may be 
adjusted as indicated in Table 1. Intra-patient dose reduction will be allowed 
depending on the type and severity of toxicity encountered.   
If dose reduction is required, reduction is permanent and will not be brought back up to 
full dose. If doses are missed due to toxicity, these will not be made up.   
Table 1a. Dose Levels for AZD5363 
Dose Level 
Daily Dose/ Route 
Dispensed As 
Schedule 
Starting 
dose level: 0 
480 mg, PO 
2 × 200-mg tablets 
1 x 80-mg tablet 
4 days on/3 days off twice a 
day on a weekly basis, for 
each 28 day cycle 
–1 
400 mg, PO 
2 x 200 mg tablet 
4 days on/3 days off twice a 
day on a weekly basis, for 
each 28 day cycle 
–2 
320 mg, PO 
4 x 80-mg tablets 
4 days on/3 days off twice a 
day on a weekly basis, for 
each 28 day cycle 
Patients requiring more than 2 dose reductions due to treatment-toxicity will be 
removed from treatment. Patients requiring treatment to be held for >4 weeks will 
be taken off treatment. 
Table 1b. Dose Levels for AZD5363 for patients continuing fulvestrant or an 
aromatase inhibitor 
Dose Level 
Daily Dose/ Route 
Dispensed As 
Schedule 
Starting 
dose level: 0 
400 mg, PO 
2 x 200 mg tablet 
4 days on/3 days off twice a 
day on a weekly basis, for 
each 28 day cycle 
–1 
320 mg, PO 
4 x 80-mg tablets 
4 days on/3 days off twice a 
day on a weekly basis, for 
each 28 day cycle 
If continuing fulvestrant or an aromatase inhibitor, patients requiring more than 1 
dose reductions due to treatment-toxicity will be removed from treatment. 
Patients requiring treatment to be held for >4 weeks will be taken off treatment. 

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Table 2: Hematologic Toxicity 
Grade 
Management/Next Dose for AZD5363 
Grade 1 
No change in dose 
Grade 2 
No change in dose 
Grade 3 
Hold* until ≤ Grade 2. Consider resuming at one dose level lower, per 
investigator discretion** 
Grade 4 
Hold* until ≤ Grade 2. Resume at one dose level lower** 
* Patients requiring AZD5363 delay of > 4 weeks should go off protocol therapy. Growth 
factor support is allowed, per investigator discretion.  Transfuse PRBC as clinically 
indicated 
** Patients requiring > 2 dose reductions of AZD5363 should go off protocol therapy. If 
continuing fulvestrant or an aromatase inhibitor, patients requiring > 1 dose reductions 
of AZD5363 should go off protocol therapy. 
Table 3: Non-Hematologic Toxicities (not hyperglycemia or rash) 
Grade  
Management/Next Dose for AZD5363 
Grade 1 
No change in dose 
Grade 2 
Hold* until ≤ Grade 1. Recommend resume at same dose level, but per 
investigator discretion. If the toxicity is deemed probably or definitely 
related to AZD5363 – and not reduced after the first occurrence - a dose 
reduction should be considered after a second recurrence, if still deemed 
probably or definitely related. 
Grade 3 
Hold* until ≤ Grade 1. Resume at one dose level lower** 
Grade 4 
Hold* until ≤ Grade 1. Resume at one dose level lower or discontinue, per 
investigator discretion** 
* Patients requiring a delay of >4 weeks will be removed from protocol therapy. 
** Patients requiring > two dose reductions will be removed from protocol therapy. If 
continuing fulvestrant or an aromatase inhibitor, patients requiring > 1 dose 
reductions of AZD5363 should go off protocol therapy. 
Recommended management of diarrhea: loperamide antidiarrheal therapy 
Dosage schedule:  4 mg at first onset, followed by 2 mg with each loose motion until 
diarrhea-free for 12 hours (maximum dosage: 16 mg/24 hours) 
Adjunct anti-diarrheal therapy is permitted and should be recorded when used. 
Recommend management of nausea and vomiting: treat with standard anti-emetics 
such as prochlorperazine or ondansetron. The use of prophylactic anti-emetics should 
be considered. Given the potential for ondansetron to increase QTc prolongation, review 
baseline QTc EKG prior to initiation of ondansetron and consider follow up EKGs on 
treatment. 
Hyperglycemia 
These guidelines are for random blood glucose results.  While these grade 
thresholds are based on CTCAE cut-offs for fasting glucose, they are applied to 
random glucose here. These are general recommendations: due consideration 
should be given to baseline values and time since food when interpreting glucose 
results.  

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It is recommended that approaches to the management of AZD5363-induced 
hyperglycaemia in diabetic patients include advice from the patient’s 
endocrinologist where appropriate. 
For CTC Grade 3 or 4 hyperglycemia, when insulin therapy is considered an 
insulin infusion is recommended. Avoid use of long acting insulin, avoid large 
boluses of short acting insulin, and observe closely for rebound hypoglycemia. 
The management recommendations described in Table 4 are based on those 
detailed by Busaidy et al21 for PI3K-AKT-mTOR pathway inhibitors. 
Table 4:  Hyperglycemia 
Grade  
Management/Next Dose for AZD5363 
Grade 1 
(<8.9 mM;  
OR <160 mg/dL) 
No change in dose 
Grade 2 
(≥8.9 mM and <13.9 mM;  
OR >160 mg/dL and < 250 mg/dL) 
No change in dose. 
Add or administer a higher dose of oral metformin  
Consider endocrionology input and home glucose 
monitoring 
If random glucose > 200 mg/dL after 2 weeks of 
metformin, continue metformin and consider adding 
sulfonylurea and titrate 
If random glucose > 200 mg/dL after additional 1 
week of metformin and sulfonylurea, consider adding 
basal insulin. Titrate off insulin when medically 
appropriate 
Grade 3 
(≥13.9 mM and <27.8mM;  
OR ≥250 mg/dL and < 500 mg/dL) 
 without symptoms, i.e. 
polyphagia, polydipsia and 
polyuria.) 
Hold* until ≤ Grade 1.  Resume at one dose level 
lower** 
Immediate endocrionology input and home glucose 
monitoring 
Begin metformin and sulfonylurea and rapidly titrate 
oral agents 
If random glucose > 200 mg/dL after additional 1 
week of metformin and sulfonylurea, consider adding 
basal insulin. Titrate off insulin when medically 
appropriate 
Grade 4 
(>=27.8 mM OR ≥500 mg/dL)  
OR 
(≥13.9 mM and <27.8mM;  
OR ≥250 mg/dL and < 500 mg/dL 
with symptoms, i.e. polyphagia, 
polydipsia and polyuria.) 
Hold* until ≤ Grade 1.  Resume at one dose level 
lower or discontinue, per investigator discretion** 
Immediate endocrionology input 
Consider intravenous fluids and/or admit if 
hypovolemic signs/symptoms 
Consider appropriate clinical management of 
hyperglycaemia per local guidelines (insulin infusion 
etc.) 
* Patients requiring a delay of > 4 weeks should go off protocol therapy. 
** Patients requiring > two dose reductions should go off protocol therapy. If continuing 
fulvestrant or an aromatase inhibitor, patients requiring > 1 dose reductions of 
AZD5363 should go off protocol therapy. 

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Table 5:  Maculo-Papular Rash 
Grade  
Management/Next Dose for AZD5363 
Grade 1 
No change in dose.  Initiate dermatological treatment, including topical 
steroid moderate strength bid and oral anti-histamine, if symptomatic. 
Grade 2 
No change in dose.  No change in dose.  Initiate dermatological treatment, 
including topical steroid moderate strength bid and oral anti-histamine, if 
symptomatic. 
Grade 3 
Hold* until ≤ Grade 2.  Initiate dermatological treatment, including oral 
steroid for up to 2 weeks and oral anti-histamine, if symptomatic.  If Grade 
≤1 and tolerable, reinstate at current dose.  If Grade 2 and tolerable, 
reinstate at one dose level lower.  If not tolerable, discontinue AZD5363. ** 
* Patients requiring a delay of > 4 weeks should go off protocol therapy. 
** Patients requiring > two dose reductions should go off protocol therapy. If continuing 
fulvestrant or an aromatase inhibitor, patients requiring > 1 dose reductions of 
AZD5363 should go off protocol therapy. 
For those patients with HR positive/HER2 negative metastatic breast cancer who 
continue to receive anti-estrogen therapy in combination with AZD5363, the anti-
estrogen therapy has a distinct toxicity profiles. While there is the possibility that 
they may share some adverse events such as fatigue or nausea and causality 
will not always be clear, dose reductions and/or delays will follow the most 
conservative approach. 
For patients with moderate hepatic impairment (defined as Child-Pugh Class B), 
including any patient who develops moderate hepatic impairment during study 
treatment, fulvestrant 250 mg should be administered intramuscularly into the 
buttock slowly (1-2 minutes) as one 250-mg injection. 
There will be no dose adjustments for aromatase inhibitors. Switching between 
aromatase inhibitors are not allowed. For instance, if the patient continues on 
letrozole and is unable to tolerate letrozole, s(he) is not allowed to switch to 
exemestane. 
If the patient is not able to tolerate the continuation of fulvestrant or an aromatase 
inhibitor, the hormone therapy should be discontinued. However, the patient may 
remain on the study and continue to take AZD5363. 
3.5 
Supportive Care  
All supportive measures consistent with optimal patient care will be given 
throughout the study. See tables for recommendations of hematologic toxicity 
(Table 2), non-hematologic toxicity (Table 3: nausea, emesis, diarrhea), 
hyperglycemia (Table 4), maculo-papular rash (Table 5). 
AZD5363 showed no evidence of phototoxicity so no special precautions are 
needed by patients with regard to sun exposure or use of sunbeds/tanning 
booths. However, investigators should be be asked to probe the possibility of 
phototoxicity when rash AEs are reported. 
3.6 
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: 
Rev. Add13 

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• 
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. 
• 
Patient withdraws consent. 
• 
Patient experiences unacceptable toxicity. 
• 
Non-protocol therapies are administered. 
• 
Disease progression 
3.7 
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 AZD5363 Treatment  
NOTE: 
In addition to the study parameters listed in the MATCH Master Protocol, the below parameters must also be 
performed for patients on AZD5363 treatment. 
NOTE: 
All assessments required prior to registration to treatment should be done ≤ 4 weeks prior to registration to 
Steps 1, 3, 5, 7, excluding the radiologic evaluation and electrocardiogram (ECG). 
Test/Assessment 
Prior to 
Registration to 
Treatment 
Treatment 
End of 
Treatment 
Follow UpF 
Every Cycle, prior 
to treatment 
C1D1, C1D4, 
and C1D11L 
Every 2 Cycles 
H&P, Weight, Vital signsA 
X 
XJ 
 
 
 
X 
Performance status 
X 
XJ 
 
 
 
X 
CBC w/diff, pltsB 
X 
XJ 
XL 
 
 
X 
Serum chemistryB,O 
X 
XJ 
XL 
 
 
X 
UrinalysisB 
X 
XJ 
XL 
 
 
 
Radiologic evaluationC 
X 
 
 
XC 
 
XF 
-HCGD 
X 
 
 
 
 
 
Toxicity AssessmentE 
 
X 
 
 
X 
XF 
Pill Count/DiaryG 
 
X 
 
 
X 
 
ECG 
XH 
XK 
 
 
 
 
Tumor biopsy and blood sample for MATCH Master ProtocolI 
 
 
 
X 
X 
 
Anti-estrogen therapyM 
X 
XN 
 
 
 
 
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. Serum Albumin, alkaline phosphatase, total bilirubin, bicarbonate, BUN, calcium, creatinine, glucose, phosphorus, potassium, SGOT[AST], 
SGPT[ALT], sodium, magnesium, and serum tumor markers (including LDH, PSA if appropriate).  For eligibility purposes, participants with 
creatinine levels above institutional normal, Cockcroft-Gault will be used to calculate creatinine clearance.  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). Urinalysis is without microscopy. CBC and serum chemistries are only required in follow-up until values return to pre-treatment 
levels or until progressive disease. Hyperglycemia management is described in Section 3.4. 
C. Disease measurements are repeated every 2 cycles for the first 26 cycles, and every 3 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 
Rev. 12/16 
Rev. 3/17 
Rev. Add13 

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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. 
D. Blood pregnancy test (women of childbearing potential) required prior to beginning treatment. 
E. 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. 
F. 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 
G. The pill calendar will be collected at the end of every cycle. The Pill Count/Diary is not required prior to Cycle 1, but is required every subsequent 
cycle. 
H. Within 8 weeks of treatment assignment. 
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: 
• 
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. 
• 
Screening biopsies for additional aMOI assessments after registration to appropriate screening step, if applicable (Step 2 or Step 4). 
• 
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. For Cycle 1, if the following tests/assessments occurred within 7 days of Day 1, they do not need to be repeated at this time point: H&P, Weight, 
Vital Signs; Performance Status; CBC w/diff, platelets; Serum chemistry; Urinalysis; Concomitant Medications. 
K. As clinically indicated. 
L. The patient will also return for C1D4 (+/- 1 day) and C1D11 (+/- 1 day) for pre-dose AZD5363 basic metabolic panel (including glucose), CBC 
w/diff, and urinalysis. It is not required that these labs be collected while the patient is fasting. Hyperglycemia management is described in 
Section 3.4. 
M. If the patient has Hormone Receptor positive, HER2 negative unresectable breast cancer, the patient is allowed to continue the fulvestrant or 
aromatase inhibitor that (s)he just progressed on. Patients who will be continuing fulvestrant or an aromatase inhibitor will be instructed to take 
AZD5363 400 mg orally daily twice a day, 4 days on/3 days off on a weekly basis for each 28 day cycle. Fulvestrant 500 mg should be 
administered intramuscularly into the buttocks slowly (1 to 2 minutes per injection) as two 250-mg injections, one in each buttock; however, for 
patients with moderate hepatic impairment (defined as Child-Pugh Class B), including any patient who develops moderate hepatic impairment 
during study treatment, fulvestrant 250 mg should be administered intramuscularly into the buttock slowly (1 to 2 minutes) as one 250-mg 

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injection. For the aromatase inhibitor, there is no modification in dosing and patients are NOT allowed to switch within class (for instance, 
letrozole to anastrazole). GnRH agonists are allowed to continue as previously administered. SERMS, such as tamoxifen or toremifene, are not 
allowed. 
N. If the patient is given Fulvestrant and/or a GnRH agonist, these should be given on D1 of the cycle (+/- 7 days). 
O. Fasting Glucose required at screening. Subsequent glucose will be checked with serum chemistry and can be non-fasting, per investigator 
discretion. 
 

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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 
AZD5363 (NSC 782347) 
5.1.1 
Other Names: AZD5363 
5.1.2 
Classification:  
Oral AKT inhibitor 
5.1.3 
Mode of Action:  
AZD5363 is a potent, oral inhibitor of kinase activity of 
serine/threonine specific protein kinase (Akt). AZD5363 inhibits 
activity of three Akt isoforms (Akt1, Akt2, Akt3), which are activated in 
different solid tumors. AKT is a hub of multiple signaling pathways 
promoting tumorigenesis, inhibiting apoptosis, promoting invasion and 
migration and is often associated with resistance to established 
cancer therapies. AZD5363 is expected to have efficacy when 
combined with cytotoxic cancer therapies or other targeted or anti-
hormonal agents. 
5.1.4 
Storage and Stability: 
Storage: Store below 30°C. 
If a storage temperature excursion is identified, promptly return 
AZD5363 to below 30°C and quarantine the supplies.  Provide a 
detailed report of the excursion (including documentation of 
temperature monitoring and duration of the excursion) to 
PMBAfterHours@mail.nih.gov for determination of suitability. 
Stability: Stability studies are ongoing. Per the manufacturer, if re-
packaging in a HDPE pharmacy bottle is necessary, assign the re-
packaged bottle a 30-day expiration date. 
5.1.5 
Dose Specifics:   
Dosing is described in Section 3.4. Starting dose is 480 mg PO BID 
twice a day on a weekly basis, (4 days on/3 days off) for a 28-day 
cycle. Patients who will be continuing fulvestrant or an aromatase 
inhibitor will be instructed to take AZD5363 400 mg orally daily twice a 
day, 4 days on/3 days off on a weekly basis for each 28 day cycle. 
5.1.6 
How Supplied:  
AstraZeneca supplies and PMB, CTEP, DCTD distributes AZD5363 
as beige film-coated tablets in 80 mg and 200 mg strengths. Tablets 
are packed in high-density polyethylene (HDPE) bottles. Each bottle is 
secured with a heat induction seal, child-resistant closure and no 
desiccant. 
• 
80 mg:7 mm round, biconvex tablets in 30-count bottles 
• 
200 mg: 9 mm round, biconvex tablets in 60-count bottles 
Each tablet contains AZD5363, microcrystalline cellulose, mannitol, 
croscarmellose cellulose and magnesium stearate. The tablet film-
coat contains polyvinyl alcohol, titanium dioxide, polyethylene glycol, 
talc, yellow iron oxide, red iron oxide and black iron oxide. 
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5.1.7 
Route of Administration:  
Oral. Take on an empty stomach at least 2 hours after a meal and 1 
hour before the next meal. 
5.1.8 
Incompatibilities:  
In vitro experiments have demonstrated, AZD5363 to be a substrate 
of uridine diphosphate glucuronosyl transferase (UGT) 1A9 and 2B7 
isoforms, which are responsible for the formation of the glucuronide 
metabolite. CYP3A4 is mainly responsible for the formation of 
monooxygenated metabolites, with contributions from CYP2C9 and 
CYP3A5. Avoid potent inhibitors or inducers of any of these enzyme 
systems. In particular, the manufacturer advises against the co-
administration of potent inhibitors or inducers of CYP 3A4/5 within 2 
weeks (3 weeks for St John’s Wort) before the first dose of study 
treatment and until 2 weeks after the last dose of study treatment. 
AZD5363 is a substrate for the P-gp transporter in vitro, but not 
BCRP. There is a potential for increased systemic exposures of 
AZD5363 by potent P-gp inhibitors. 
In vitro experiments indicate that AZD5363 is a reversible inhibitor of 
CYP3A4/5, 2C9, 2D6 and UGT1A1 and to a lesser extent CYP 2B6 
and 2C19, but the agent was found not to be an inhibitor for other 
CYP isoforms tested (1A2, 2A6, 2C8, 2E1).  Avoid co-administration 
of CYP 3A4/5, 2C9 and 2D6 sensitive substrates in patients from the 
time they enter screening until 2 weeks after the last dose of study 
treatment since this may result in increased exposure of these 
substrates. 
AZD5363 is not a significant inducer of CYP3A4/5 enzyme activity 
and was found to have no effect on activity of CYP 1A1/2, 2B6 or 
pregnane X receptor (PXR). 
In vitro data indicate AZD5363 inhibits the organic anion-transporting 
polypeptides (OATP1B1 and OATP1B3), OAT3 and MATE2K and 
therefore suggests there is potential drug-drug interaction with 
sensitive substrates. These transporters are implicated in the 
distribution and clearance of many of the statins. Of the statins that 
are minimally affected by CYP3A4 inhibition and recommended for 
use in patients receiving AZD5363, rosuvastatin and pravastatin (but 
not fluvastatin) can be affected by OATP1B1 and OATP1B3 inhibition. 
Based on current data, the AUC of these drugs may be increased by 
1.3-fold for pravastatin and 1.5-fold for rosuvastatin.  The 
manufacturer recommends that doses of rosuvastatin be capped to 10 
mg once daily and pravastatin to 40 mg once daily when combined 
with AZD5363 starting 2 weeks prior and ending 2 weeks after 
AZD5363 treatment. 
AZD5363 is an inhibitor of organic cationic transporter 2 (OCT2) and 
MATE1. There is a potential for drug-drug interactions with sensitive 
substrates, such as metformin; therefore, use metformin with caution 
in patients who are taking AZD5363. 
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AZD5363 is not an inhibitor of P-glycoprotein (P-gp) and is not 
expected to affect sensitive P-gp substrates. This agent is an inhibitor 
of human efflux transporter breast cancer resistance protein (BCRP), 
although the risk of causing drug-drug interactions with substrates of 
this transporter is considered to be low per the manufacturer. 
Appropriate medical judgment is required. Refer to Appendix III for a 
sample list. 
5.1.9 
Patient Care Implications 
Advise women study participants of reproductive potential to use 
effective contraception while receiving study treatment and for at least 
4 months after the last dose of AZD5363. Men study participants are 
required to use barrier methods of contraception and avoid sperm 
donation throughout the study and for 4 months after the last dose of 
AZD5363. 
It is not known whether the preclinical changes seen in the male 
animal reproductive organs, after treatment with AZD5363, will be fully 
reversible or will permanently affect the ability to produce healthy 
sperm following treatment. Therefore, if male patients wish to father 
children they should be advised to arrange for freezing of sperm 
samples prior to the start of study treatment. 
5.1.10 
Side Effects  
See Section 3.3 for side effects. 
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6. 
Translational Studies 
Please refer to the MATCH Master Protocol for information on the Translational Studies.  
7. 
References 
1. 
Davies BR, Greenwood H, Dudley P, et al. Preclinical pharmacology of AZD5363, 
an inhibitor of AKT: pharmacodynamics, antitumor activity, and correlation of 
monotherapy activity with genetic background. Mol Cancer Ther 2012;11:873-87. 
2. 
Li J, Davies BR, Han S, et al. The AKT inhibitor AZD5363 is selectively active in 
PI3KCA mutant gastric cancer, and sensitizes a patient-derived gastric cancer 
xenograft model with PTEN loss to Taxotere. J Transl Med 2013;11:241. 
3. 
U. B. A pharmacokinetically (PK) and pharmacodynamically (PD) driven phase I 
trial of the pan-AKT inhibitor AZD5363 with expansion cohorts in PIK3CA mutant 
breast and gynecological cancers. J Clin Oncol 33, 2015 (suppl; abstr 2500) 
http://abstractsascoorg/156/AbstView_156_146991html ASCO 2015. 
4. 
Hyman DM, et al. AZD5363, a catayltic pan-AKT inhibitior in AKT1 E17K mutation 
positive advanced solid tumors. AACR-NCI-EORTC Conference on Molcular 
Targets and Cancer Therapeutics. November 201.5 
5. 
Ribas et al. AKT AZD5363 Influences Estrogen Receptor Function in Endocrine-
Resistant Breast Cancer and Synergizes with Fulvestrant (ICI82780) In Vivo. Mol 
Cancer Ther 2015; 14(9): 2035-48. 
6. 
Fruman DA, Meyers RE, Cantley LC. Phosphoinositide kinases. Annu Rev 
Biochem 1998;67:481-507. 
7. 
Crowell JA, Steele VE, Fay JR. Targeting the AKT protein kinase for cancer 
chemoprevention. Mol Cancer Ther 2007;6:2139-48. 
8. 
Sarbassov DD, Guertin DA, Ali SM, Sabatini DM. Phosphorylation and regulation 
of AKT/PKB by the rictor-mTOR complex. Science 2005;307:1098-101. 
9. 
Blanco-Aparicio C, Renner O, Leal JF, Carnero A. PTEN, more than the AKT 
pathway. Carcinogenesis 2007;28:1379-86. 
10. 
Gottlieb TM, Leal JF, Seger R, Taya Y, Oren M. Cross-talk between AKT, p53 and 
Mdm2: possible implications for the regulation of apoptosis. Oncogene 
2002;21:1299-303. 
11. 
Dan HC, Ebbs A, Pasparakis M, Van Dyke T, Basseres DS, Baldwin AS. AKT-
dependent activation of mTORC1 complex involves phosphorylation of mTOR 
(mammalian target of rapamycin) by IkappaB kinase alpha (IKKalpha). J Biol Chem 
2014;289:25227-40. 
12. 
Kandoth C, McLellan MD, Vandin F, et al. Mutational landscape and significance 
across 12 major cancer types. Nature 2013;502:333-9. 
13. 
Boyault S, Drouet Y, Navarro C, et al. Mutational characterization of individual 
breast tumors: TP53 and PI3K pathway genes are frequently and distinctively 
mutated in different subtypes. Breast Cancer Res Treat 2012;132:29-39. 
14. 
Stemke-Hale K, Gonzalez-Angulo AM, Lluch A, et al. An integrative genomic and 
proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer. Cancer 
Res 2008;68:6084-91. 

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Version Date: July 10, 2019 
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15. 
Kumar A, Purohit R. Cancer associated E17K mutation causes rapid 
conformational drift in AKT1 pleckstrin homology (PH) domain. PLoS One 
2013;8:e64364. 
16. 
Altomare DA, Testa JR. Perturbations of the AKT signaling pathway in human 
cancer. Oncogene 2005;24:7455-64. 
17. 
Banerji S, Cibulskis K, Rangel-Escareno C, et al. Sequence analysis of mutations 
and translocations across breast cancer subtypes. Nature 2012;486:405-9. 
18. 
Mosquera JM, Varma S, Pauli C, et al. MAGI3-AKT3 fusion in breast cancer 
amended. Nature 2015;520:E11-2. 
19. 
Hammond MEH, Hayes DF, Dowsett M, et al. American Society of Clinical   
Oncology/College of American Pathologists guideline recommendations for 
immunohistochemical testing of estrogen and progesterone receptors in breast 
cancer. J Clin Oncol. 2010;28:2784. 
20. 
Wolff AC, Hammond MEH, Hicks DG, Dowsett M, McShane LM, Allison KH, Allred 
DC, Bartlett JMS, Bilous M, Fitzgibbons P, Hanna W, Jenkins RB, Mangu PB, Paik 
S, Perez EA, Press MF, Spears PA, Vance GH, Viale G, Hayes DF. 
Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in 
Breast Cancer: American Society of Clinical Oncology/College of American 
Pathologists Clinical Practice Guideline Update. J Clin Oncol. 2013;31(31):3997-
4013. 
21. 
Busaidy NL, Farooki A, Dowlati A, et al. Management of Metabolic Effects 
Associated with Anticancer Agents Targeting the PI3K-Akt-mTor Pathway. J Clin 
Oncol. 2012; 30 (23): 2919-2928. 

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Version Date: July 10, 2019 
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Molecular Analysis for Therapy Choice (MATCH) 
MATCH Treatment Subprotocol Y: AZD5363 in Patients with Tumors with AKT Mutations 
Appendix I 
 
Patient Pill Calendar 
Storage: Store at Room Temperature 
Pill Calendar Directions 
1. Take your scheduled dose of each tablet. 
2. Please bring the empty bottle or any leftover tablets and your pill calendar to your 
next clinic visit. 
3. All doses of AZD5363 should be taken with water only, on an empty stomach, no 
food for at least 2 hours before a dose and for at least 1 hour after. 
4. AZD5363 is to be taken twice per day for 4 days in a row followed by 3 days where 
no AZD5363 is taken. 
5. If you vomit after AZD5363 dosing, do not retake new tablet(s), but continue to take 
the next dose 12 hours later. 
6. If you miss a dose, you may take the dose up to a maximum of 2 hours after the 
scheduled dose time. If greater than 2 hours after the scheduled dose time, the 
missed dose should not be made up. 
7. If you need to take the dose earlier for whatever reason, you can take the dose up to 
2 hours earlier than the scheduled dose time.  
 
 
 
Rev. 3/17 

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Patient Pill Calendar 
This is a calendar on which you are to record the time and number of tablets you take 
each day.  You should take your scheduled dose of each tablet. Note the times and the 
number of tablets that you take each day. If you develop any side effects, please 
record them and anything you would like to tell the doctor in the space provided.  Bring 
any unused tablets and your completed pill calendar to your doctor’s visits. 
AZD5363 
DAY  
Date 
Time tablets 
taken 
Number of 
tablets taken 
(80 mg) 
Number of 
tablets taken 
(200 mg) 
Use the space below to 
make notes about things 
you would like to tell the 
doctor (including unusual 
symptoms you experience, 
other medicine you have 
taken and anything else you 
think would be of interest.) 
Month 
Day 
Year 
AM 
PM 
AM 
PM 
AM 
PM 
1 
 
 
 
 
 
 
 
 
 
 
2 
 
 
 
 
 
 
 
 
 
 
3 
 
 
 
 
 
 
 
 
 
 
4 
 
 
 
 
 
 
 
 
 
 
5 
 
 
 
 
 
 
 
 
 
 
6 
 
 
 
 
 
 
 
 
 
 
7 
 
 
 
 
 
 
 
 
 
 
8 
 
 
 
 
 
 
 
 
 
 
9 
 
 
 
 
 
 
 
 
 
 
10 
 
 
 
 
 
 
 
 
 
 
11 
 
 
 
 
 
 
 
 
 
 
12 
 
 
 
 
 
 
 
 
 
 
13 
 
 
 
 
 
 
 
 
 
 
14 
 
 
 
 
 
 
 
 
 
 
15 
 
 
 
 
 
 
 
 
 
 
16 
 
 
 
 
 
 
 
 
 
 
17 
 
 
 
 
 
 
 
 
 
 
18 
 
 
 
 
 
 
 
 
 
 
19 
 
 
 
 
 
 
 
 
 
 
20 
 
 
 
 
 
 
 
 
 
 
21 
 
 
 
 
 
 
 
 
 
 
22 
 
 
 
 
 
 
 
 
 
 
23 
 
 
 
 
 
 
 
 
 
 
24 
 
 
 
 
 
 
 
 
 
 
25 
 
 
 
 
 
 
 
 
 
 
26 
 
 
 
 
 
 
 
 
 
 
27 
 
 
 
 
 
 
 
 
 
 
28 
 
 
 
 
 
 
 
 
 
 
Patient Signature: _________________________________________ Date: _____________ 

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Version Date: July 10, 2019 
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Patient Pill Calendar (If HR positive/HER2 negative metastatic breast cancer and 
continuing an aromatase inhibitor) 
This is a calendar on which you are to record the time and number of tablets you take each day. 
You should take your scheduled dose of each tablet. Note the times and the number of 
tablets that you take each day. AZD5363 is taken 4 days on/3 days off. The aromatase 
Inhibitor is taken daily. If you develop any side effects, please record them and anything you 
would like to tell the doctor in the space provided.  Bring any unused tablets and your completed 
pill calendar to your doctor’s visits. 
 
AZD5363 
Aromatase 
Inhibitor 
Name: 
Use the space below to 
make notes about things 
you would like to tell the 
doctor (including unusual 
symptoms you experience, 
other medicine you have 
taken and anything else you 
think would be of interest.) 
DAY 
Date 
Time 
tablets 
taken 
Number of 
tablets 
taken 
(80 mg) 
Number of 
tablets 
taken 
(200 mg) 
Time 1 
tablet 
taken 
Month  Day   Year 
AM 
PM 
AM 
PM 
AM PM 
AM 
PM 
1 
 
 
 
 
 
 
 
 
 
 
 
 
2 
 
 
 
 
 
 
 
 
 
 
 
 
3 
 
 
 
 
 
 
 
 
 
 
 
 
4 
 
 
 
 
 
 
 
 
 
 
 
 
5 
 
 
 
 
 
 
 
 
 
 
 
 
6 
 
 
 
 
 
 
 
 
 
 
 
 
7 
 
 
 
 
 
 
 
 
 
 
 
 
8 
 
 
 
 
 
 
 
 
 
 
 
 
9 
 
 
 
 
 
 
 
 
 
 
 
 
10 
 
 
 
 
 
 
 
 
 
 
 
 
11 
 
 
 
 
 
 
 
 
 
 
 
 
12 
 
 
 
 
 
 
 
 
 
 
 
 
13 
 
 
 
 
 
 
 
 
 
 
 
 
14 
 
 
 
 
 
 
 
 
 
 
 
 
15 
 
 
 
 
 
 
 
 
 
 
 
 
16 
 
 
 
 
 
 
 
 
 
 
 
 
17 
 
 
 
 
 
 
 
 
 
 
 
 
18 
 
 
 
 
 
 
 
 
 
 
 
 
19 
 
 
 
 
 
 
 
 
 
 
 
 
20 
 
 
 
 
 
 
 
 
 
 
 
 
21 
 
 
 
 
 
 
 
 
 
 
 
 
22 
 
 
 
 
 
 
 
 
 
 
 
 
23 
 
 
 
 
 
 
 
 
 
 
 
 
24 
 
 
 
 
 
 
 
 
 
 
 
 
25 
 
 
 
 
 
 
 
 
 
 
 
 
26 
 
 
 
 
 
 
 
 
 
 
 
 
27 
 
 
 
 
 
 
 
 
 
 
 
 
28 
 
 
 
 
 
 
 
 
 
 
 
 
Patient Signature: __________________________________ Date: _____________ 
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Molecular Analysis for Therapy Choice (MATCH) 
MATCH Treatment Subprotocol Y: AZD5363 in Patients with Tumors with AKT Mutations 
Appendix II 
 
Actionable Mutations for Sub-Protocol EAY131-Y 
List of inclusion variants: 
Gene Name 
Variant ID 
Variant Description 
Level of Evidence Code 
AKT1 
p.E17K 
AKT mutation 
Level 2A 
 
List of exclusion variants 
Gene 
Name 
Variant ID 
Variant 
Description 
Level of Evidence Code 
BRAF 
MACF1-BRAF.M60B9 
Fusion 
1 
BRAF 
TRIM24-BRAF.T9B9.1 
Fusion 
1 
BRAF 
SLC12A7-BRAF.S17B11 
Fusion 
1 
BRAF 
CLIP2-BRAF.C6B11 
Fusion 
1 
BRAF 
KIAA1549-
BRAF.K18B9.COSF511 
Fusion 
1 
BRAF 
TRIM24-BRAF.T3B11 
Fusion 
1 
BRAF 
KIAA1549-
BRAF.K15B10.COSF1283.1 
Fusion 
1 
BRAF 
CEP89-BRAF.C16B9 
Fusion 
1 
BRAF 
ATG7-BRAF.A18B9 
Fusion 
1 
BRAF 
RNF130-
BRAF.R3B9.COSF1483 
Fusion 
1 
BRAF 
SND1-BRAF.S11B11 
Fusion 
1 
BRAF 
KLHL7-BRAF.K5B9 
Fusion 
1 
BRAF 
ERC1-BRAF.E12B10 
Fusion 
1 
BRAF 
AP3B1-BRAF.A22B9 
Fusion 
1 
BRAF 
AKAP9-BRAF.A22B9 
Fusion 
1 
BRAF 
ARMC10-BRAF.A4B11 
Fusion 
1 
BRAF 
KIAA1549-BRAF.K9B9 
Fusion 
1 
BRAF 
AGK-BRAF.A2B8 
Fusion 
1 
BRAF 
SOX6-BRAF.S6B9 
Fusion 
1 
BRAF 
AKAP9-BRAF.A28B9 
Fusion 
1 
BRAF 
FAM131B-
BRAF.F2B9.COSF1189.1 
Fusion 
1 
BRAF 
BRAF-AP3B1.B8A23 
Fusion 
1 
BRAF 
GATM-BRAF.G2B11 
Fusion 
1 
BRAF 
CCDC6-BRAF.C1B9 
Fusion 
1 
BRAF 
AKAP9-
BRAF.A8B9.COSF1013.1 
Fusion 
1 
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Gene 
Name 
Variant ID 
Variant 
Description 
Level of Evidence Code 
BRAF 
TRIM24-BRAF.T11B2 
Fusion 
1 
BRAF 
MZT1-BRAF.M2B11 
Fusion 
1 
BRAF 
MKRN1-
BRAF.M4B11.COSF1444 
Fusion 
1 
BRAF 
SLC45A3-
BRAF.S1B8.COSF871 
Fusion 
1 
BRAF 
BCL2L11-BRAF.B3B10 
Fusion 
1 
BRAF 
ZC3HAV1-BRAF.Z7B11 
Fusion 
1 
BRAF 
CUX1-BRAF.C10B9 
Fusion 
1 
BRAF 
STRN3-BRAF.S3B10 
Fusion 
1 
BRAF 
DYNC1I2-BRAF.D7B10 
Fusion 
1 
BRAF 
KCTD7-BRAF.K4B8 
Fusion 
1 
BRAF 
SND1-BRAF.S9B9 
Fusion 
1 
BRAF 
UBN2-BRAF.U3B11 
Fusion 
1 
BRAF 
SND1-BRAF.S10B11 
Fusion 
1 
BRAF 
KIAA1549-
BRAF.K14B9.COSF483 
Fusion 
1 
BRAF 
KIAA1549-BRAF.K12B11 
Fusion 
1 
BRAF 
EML4-BRAF.E6B10 
Fusion 
1 
BRAF 
GHR-BRAF.G1B10 
Fusion 
1 
BRAF 
PAPSS1-BRAF.P5B9.1 
Fusion 
1 
BRAF 
KIAA1549-
BRAF.K17B10.COSF509 
Fusion 
1 
BRAF 
FAM114A2-BRAF.F9B11 
Fusion 
1 
BRAF 
TMEM178B-BRAF.T2B9 
Fusion 
1 
BRAF 
RBMS3-BRAF.R11B11 
Fusion 
1 
BRAF 
AGAP3-BRAF.A9B9 
Fusion 
1 
BRAF 
FAM131B-
BRAF.F1B10.COSF1191 
Fusion 
1 
BRAF 
GTF2I-BRAF.G4B10 
Fusion 
1 
BRAF 
SND1-BRAF.S18B10 
Fusion 
1 
BRAF 
HERPUD1-BRAF.H4B7 
Fusion 
1 
BRAF 
TRIM24-BRAF.T10B9 
Fusion 
1 
BRAF 
KDM7A-BRAF.K11B11 
Fusion 
1 
BRAF 
RAD18-BRAF.R7B10 
Fusion 
1 
BRAF 
BRAF-MACF1.B8M15 
Fusion 
1 
BRAF 
AGTRAP-
BRAF.A5B8.COSF828.1 
Fusion 
1 
BRAF 
KIAA1549-
BRAF.K14B11.COSF1226 
Fusion 
1 
BRAF 
SND1-BRAF.S14B9 
Fusion 
1 
BRAF 
C7orf73-BRAF.C2B9 
Fusion 
1 
BRAF 
CDC27-BRAF.C16B9.1 
Fusion 
1 

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Version Date: July 10, 2019 
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Gene 
Name 
Variant ID 
Variant 
Description 
Level of Evidence Code 
BRAF 
TANK-BRAF.T4B9 
Fusion 
1 
BRAF 
LSM14A-BRAF.L9B9 
Fusion 
1 
BRAF 
CLCN6-
BRAF.C2B11.COSF1440 
Fusion 
1 
BRAF 
MKRN1-BRAF.M4B9 
Fusion 
1 
BRAF 
ERC1-BRAF.E17B8 
Fusion 
1 
BRAF 
TMPRSS2-BRAF.T3B11 
Fusion 
1 
BRAF 
KIAA1549-BRAF.K16B10 
Fusion 
1 
BRAF 
CCDC91-BRAF.C11B9 
Fusion 
1 
BRAF 
KIAA1549-
BRAF.K15B9.COSF481.1 
Fusion 
1 
BRAF 
KIAA1549-
BRAF.K15B11.COSF485.1 
Fusion 
1 
BRAF 
KIAA1549-
BRAF.K12B9.COSF1474 
Fusion 
1 
BRAF 
MYRIP-BRAF.M16B9 
Fusion 
1 
BRAF 
LSM12-BRAF.L3B9 
Fusion 
1 
BRAF 
TRIM24-BRAF.T3B10 
Fusion 
1 
BRAF 
PLIN3-BRAF.P1B9 
Fusion 
1 
BRAF 
NUDCD3-BRAF.N4B9 
Fusion 
1 
BRAF 
GNAI1-
BRAF.G1B10.COSF1442 
Fusion 
1 
BRAF 
BBS9-BRAF.B19B4 
Fusion 
1 
BRAF 
CUL1-BRAF.C7B9 
Fusion 
1 
BRAF 
BAIAP2L1-BRAF.B12B9 
Fusion 
1 
BRAF 
AKAP9-BRAF.A7B11 
Fusion 
1 
BRAF 
KIAA1549-BRAF.K13B9 
Fusion 
1 
BRAF 
AKAP9-BRAF.A21B10 
Fusion 
1 
BRAF 
SND1-BRAF.S16B9.1 
Fusion 
1 
BRAF 
CCNY-BRAF.C1B10 
Fusion 
1 
BRAF 
FXR1-BRAF.F13B10 
Fusion 
1 
BRAF 
ZKSCAN5-BRAF.Z2B9 
Fusion 
1 
BRAF 
BRAF-CIITA.B9C6 
Fusion 
1 
BRAF 
NUB1-BRAF.N3B9 
Fusion 
1 
BRAF 
SND1-BRAF.S14B11 
Fusion 
1 
BRAF 
KCTD7-BRAF.K3B8 
Fusion 
1 
BRAF 
BRAF-SUGCT.B1S13 
Fusion 
1 
BRAF 
BRAF-MRPS33.B1M2 
Fusion 
1 
BRAF 
ZC3HAV1-BRAF.Z3B10 
Fusion 
1 
BRAF 
TAX1BP1-BRAF.T8B11.1 
Fusion 
1 
BRAF 
TRIM24-BRAF.T5B8 
Fusion 
1 
BRAF 
SOX6-BRAF.S5B9 
Fusion 
1 
BRAF 
AGAP3-BRAF.A10B11 
Fusion 
1 

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Gene 
Name 
Variant ID 
Variant 
Description 
Level of Evidence Code 
BRAF 
NUP214-BRAF.N21B10 
Fusion 
1 
BRAF 
MAD1L1-BRAF.M16B9 
Fusion 
1 
BRAF 
RP2-BRAF.R3B10 
Fusion 
1 
BRAF 
SND1-BRAF.S10B9 
Fusion 
1 
BRAF 
ZSCAN30-BRAF.Z3B10 
Fusion 
1 
BRAF 
EPS15-BRAF.E22B10 
Fusion 
1 
BRAF 
BTF3L4-BRAF.B3B11 
Fusion 
1 
BRAF 
FAM131B-
BRAF.F3B9.COSF1193 
Fusion 
1 
BRAF 
BRAF-SLC26A4.B3S7 
Fusion 
1 
BRAF 
FCHSD1-
BRAF.F13B9.COSF403 
Fusion 
1 
BRAF 
MAD1L1-BRAF.M17B10 
Fusion 
1 
BRAF 
TRIM4-BRAF.T6B10 
Fusion 
1 
BRAF 
RNF11-BRAF.R1B11 
Fusion 
1 
BRAF 
SND1-BRAF.S9B2 
Fusion 
1 
BRAF 
COSM1111  
BRAF mutation 
p.G464R 
BRAF 
COSM1125 
BRAF mutation 
p.L597Q 
BRAF 
COSM1126 
BRAF mutation 
p.L597S 
BRAF 
COSM1127 
BRAF mutation 
p.V600R 
BRAF 
COSM1133046  
BRAF mutation 
p.Y472C 
BRAF 
COSM1448615 
BRAF mutation 
p.G464R 
BRAF 
COSM1583010 
BRAF mutation 
p.D594A 
BRAF 
COSM1583011 
BRAF mutation 
p.V600R 
BRAF 
COSM211600 
BRAF mutation 
p.D594N 
BRAF 
COSM21549  
BRAF mutation 
p.A598V 
BRAF 
COSM21612 
BRAF mutation 
p.F595L 
BRAF 
COSM253328  
BRAF mutation 
p.G466R 
BRAF 
COSM27639 
BRAF mutation 
p.D594N 
BRAF 
COSM308550 
BRAF mutation 
p.V600D 
BRAF 
COSM447  
BRAF mutation 
p.R462I 
BRAF 
COSM448 
BRAF mutation 
p.I463S 
BRAF 
COSM449 
BRAF mutation 
p.G464E 
BRAF 
COSM450 
BRAF mutation 
p.G464V 
BRAF 
COSM451 
BRAF mutation 
p.G466V 
BRAF 
COSM452 
BRAF mutation 
p.G466A 
BRAF 
COSM459 
BRAF mutation 
p.G469V 
BRAF 
COSM460 
BRAF mutation 
p.G469A 
BRAF 
COSM461 
BRAF mutation 
p.G469E 
BRAF 
COSM462 
BRAF mutation 
p.N581S 
BRAF 
COSM463 
BRAF mutation 
p.E586K 
BRAF 
COSM466 
BRAF mutation 
p.D594V 

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Version Date: July 10, 2019 
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Gene 
Name 
Variant ID 
Variant 
Description 
Level of Evidence Code 
BRAF 
COSM467 
BRAF mutation 
p.D594G 
BRAF 
COSM468 
BRAF mutation 
p.F595L 
BRAF 
COSM469  
BRAF mutation 
p.G596R 
BRAF 
COSM470  
BRAF mutation 
p.L597V 
BRAF 
COSM471 
BRAF mutation 
p.L597R 
BRAF 
COSM472 
BRAF mutation 
p.T599I 
BRAF 
COSM473 
BRAF mutation 
p.V600K 
BRAF 
COSM474 
BRAF mutation 
p.V600R 
BRAF 
COSM476 
BRAF mutation 
p.V600E 
BRAF 
COSM477 
BRAF mutation 
p.V600D 
BRAF 
COSM478 
BRAF mutation 
p.K601E 
BRAF 
COSM53198 
BRAF mutation 
p.F595L 
HRAS 
COSM480 
HRAS mutation 
p.G12S 
HRAS 
COSM481 
HRAS mutation 
p.G12C 
HRAS 
COSM482 
HRAS mutation 
p.G12R 
HRAS 
COSM483 
HRAS mutation 
p.G12V 
HRAS 
COSM484 
HRAS mutation 
p.G12D 
HRAS 
COSM485 
HRAS mutation 
p.G12A 
HRAS 
COSM486 
HRAS mutation 
p.G13R 
HRAS 
COSM487 
HRAS mutation 
p.G13S 
HRAS 
COSM488 
HRAS mutation 
p.G13C 
HRAS 
COSM489 
HRAS mutation 
p.G13V 
HRAS 
COSM490 
HRAS mutation 
p.G13D 
HRAS 
COSM496 
HRAS mutation 
p.Q61K 
HRAS 
COSM497 
HRAS mutation 
p.Q61E 
HRAS 
COSM498 
HRAS mutation 
p.Q61L 
HRAS 
COSM499 
HRAS mutation 
p.Q61R 
HRAS 
COSM500 
HRAS mutation 
p.Q61P 
HRAS 
COSM502 
HRAS mutation 
p.Q61H 
HRAS 
COSM503 
HRAS mutation 
p.Q61H 
KRAS 
COSM13643 
KRAS mutation 
p.G12N 
KRAS 
COSM19404 
KRAS mutation 
p. A146T 
KRAS 
COSM30567 
KRAS mutation 
p.G13E 
KRAS 
COSM512 
KRAS mutation 
p.G12F 
KRAS 
COSM514 
KRAS mutation 
p.G12L 
KRAS 
COSM516 
KRAS mutation 
p.G12C 
KRAS 
COSM517 
KRAS mutation 
p.G12S 
KRAS 
COSM518 
KRAS mutation 
p.G12R 
KRAS 
COSM520 
KRAS mutation 
p.G12V 
KRAS 
COSM521 
KRAS mutation 
p.G12D 
KRAS 
COSM522 
KRAS mutation 
p.G12A 

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Version Date: July 10, 2019 
41 
Gene 
Name 
Variant ID 
Variant 
Description 
Level of Evidence Code 
KRAS 
COSM527 
KRAS mutation 
p.G13C 
KRAS 
COSM528 
KRAS mutation 
p.G13S 
KRAS 
COSM529 
KRAS mutation 
p.G13R 
KRAS 
COSM532 
KRAS mutation 
p.G13D 
KRAS 
COSM533 
KRAS mutation 
p.G13A 
KRAS 
COSM534 
KRAS mutation 
p.G13V 
KRAS 
COSM538 
KRAS mutation 
p.G15S 
KRAS 
COSM539 
KRAS mutation 
p.G15D 
KRAS 
COSM549 
KRAS mutation 
p.Q61K 
KRAS 
COSM550 
KRAS mutation 
p.Q61E 
KRAS 
COSM551 
KRAS mutation 
p.Q61P 
KRAS 
COSM552 
KRAS mutation 
p.Q61R 
KRAS 
COSM553 
KRAS mutation 
p.Q61L 
KRAS 
COSM554 
KRAS mutation 
p.Q61H 
KRAS 
COSM555 
KRAS mutation 
p.Q61H 
KRAS 
COSM87280 
KRAS mutation 
p.G13E 
NRAS 
COSM561 
NRAS mutation 
p.G12R 
NRAS 
COSM562 
NRAS mutation 
p.G12C 
NRAS 
COSM563 
NRAS mutation 
p.G12S 
NRAS 
COSM564 
NRAS mutation 
p.G12D 
NRAS 
COSM565 
NRAS mutation 
p.G12A 
NRAS 
COSM566 
NRAS mutation 
p.G12V 
NRAS 
COSM569 
NRAS mutation 
p.G13R 
NRAS 
COSM570 
NRAS mutation 
p.G13C 
NRAS 
COSM571 
NRAS mutation 
p.G13S 
NRAS 
COSM573 
NRAS mutation 
p.G13D 
NRAS 
COSM574 
NRAS mutation 
p.G13V 
NRAS 
COSM575 
NRAS mutation 
p.G13A 
NRAS 
COSM580 
NRAS mutation 
p.Q61K 
NRAS 
COSM581 
NRAS mutation 
p.Q61E 
NRAS 
COSM582 
NRAS mutation 
p.Q61P 
NRAS 
COSM583 
NRAS mutation 
p.Q61L 
NRAS 
COSM584 
NRAS mutation 
p.Q61R 
NRAS 
COSM585 
NRAS mutation 
p.Q61H 
NRAS 
COSM586 
NRAS mutation 
p.Q61H 
 

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Molecular Analysis for Therapy Choice (MATCH) 
MATCH Treatment Subprotocol Y: AZD5363 in Patients with Tumors with AKT Mutations 
Appendix III 
 
CYP3A4 Strong Inducers and Potent Inhibitors 
Because the lists of these agents are constantly changing, it is important to regularly 
consult a frequently-updated list such as Facts and Comparisons or Lexicomp; medical 
reference texts such as the Physicians’ Desk Reference may also provide this 
information. The Principal Investigator should be alerted if the subject is taking any agent 
on these lists. Appropriate medical judgment is required. 
CYP3A4 Inducing Agents: 
Ketoconazole 
 
Mebefradil 
Protease inhibitors (danoprevir, ritonavir, 
Itraconazole 
saquinavir, indanavir, tapranavir, 
 
Posaconazole 
telaprevir, elvitegravir, lopinavir, 
 
Voriconazole 
nelfinavir, bocepravir) 
 
Clarithromycin 
Cobicistat 
 
Telithromycin 
Conivaptan 
 
Troleandomycin 
Nefazodone 
 
 
CYP3A4 Potent Inhibitors: 
Phenobarbital 
 
Rifabutin 
Carbamazepine  
 
Mitotane 
Phenytoin 
Enzalutamide 
Rifampicin 
St John’s Wort 
CYP2D6 Sensitive Substrates: 
Amitryptyline 
 
Nebivolol 
Atomoxetine 
 
Nefazodone 
Cenlafaxine 
 
Paroxetine 
Desipramine 
 
Perphenazine 
Dextromethorphan 
 
Trimipramine 
Doxepin 
 
Tolterodine 
Metoprolol 
 
Tropisetron 
Venlafaxine 
CYP2D6 Substrates with Narrow Therapeutic Range: 
Thioridiazine 
 

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Molecular Analysis for Therapy Choice (MATCH) 
MATCH Treatment Subprotocol Y: AZD5363 in Patients with Tumors with AKT Mutations 
Appendix IV 
 
PI3K/AKT inhibitors in development 
The lists of these agents are constantly changing.  This may not be a comprehensive list. 
PI3K inhibitors in development: 
Drug:  
Company 
Alt. Names 
Targets 
BKM-120 
Novartis 
buparlisib 
Pan-p110 isoforms 
BYL719 
Novartis 
 
p110-α 
BEZ235 
Novartis 
 
Dual mTOR and pan-p110 
CAL-101 
Calistoga 
idelalisib 
p110-δ 
IPI-145 
Infinity  
 
p110-δ,-γ 
GDC-0941 
Genentech 
Pictilisib 
Pan-p110 isoforms 
GDC-0980 
Genentech 
Apitolisib 
Dual mTOR and pan-p110 
GDC-0032 
Genentech 
 
p110-α, -δ,-γ 
BAY 80-6946 
Bayer 
copanlisib  
p110-α,-β 
PX-866 
Oncothyreon 
 
Pan-p110 isoforms 
XL147 
Exelixis 
SAR245408 
Pan-p110 isoforms 
XL765 
Exelixis 
SAR245409 
Dual mTOR and pan-p110 
AMG319 
Amgen 
 
p110-δ 
PF-05212384 
Pfizer 
PKI-587 
Dual mTOR and p110-α 
PF-04691502 
Pfizer 
 
Dual mTOR and pan-p110 
GSK2126458 
GlaxoSmithKline 
GSK458 
Dual mTOR and pan-p110 
BGT-226 
Novartis 
 
Dual mTOR and pan-p110 
SF1126 
Semafore 
LY294002 
p85 and Pan-p110 isoforms 
ZSTK474 
Zenyaku Kogyo  
 
Pan-p110 isoforms 
GSK2636771 
GlaxoSmithKline 
 
p110-β 
GSK2269557 
GlaxoSmithKline 
 
p110-α 
TGR-1202 
TG therapeutics 
RP5264 
p110-δ 
MLN1117 
Millennium 
INK1117 
p110-α 
CUDC-907 
Curis 
 
Dual HDAC (class I and IIB) and p110-α,-β, -δ 
P7170 
Piramal Enterprises 
 
PI3K/mTOR/ALK-1/DNA-PK 
RP-6530 
Rhizen 
 
p110-δ,-γ 
VS-5584 
Verastem 
SB2343 
Dual mTOR and pan-p110 
WX-037 
WILEX 
 
Pan-p110 isoforms 

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AKT inhibitors in development: 
Drug:  
Company 
Alt. Names 
Targets 
MK-2206 
Merck 
 
Pan-AKT isoforms 
GSK-690693 
GlaxoSmithKline 
 
Pan-AKT isoforms 
GDC-0068 
Genentech 
ipatasertib 
Pan-AKT isoforms 
KRX-0401 
Keryx 
perifosine 
Dual AKT and PI3K inhibitor 
DNE3 
 
 
Pan-AKT isoforms 
ONC-201 
Oncoceutics 
 
Dual AKT and ERK inhibitor 
BAY-1125976 
Bayer 
 
AKT1,2  
GSK-2141795 
GlaxoSmithKline 
uprosertib 
Pan-AKT isoforms 
GSK-2110183 
GlaxoSmithKline 
afuresertib  
Pan-AKT isoforms 
AZD-5363 
AstraZeneca 
 
Pan-AKT isoforms 
SR-13668 
 
 
AKT, 12-LOX 
MSC-2363318A 
Merck Serono 
 
Dual p70S6K/pan-AKT inhibitor 
LY-2780301 
Lilly 
 
Dual p70S6K/pan-AKT inhibitor 
VD-0002 
Vioquest 
triciribine 
Pan-AKT isoforms 
AG1343 
 
nelfinavir; 
Viracept 
HIV protease inhibitor, AKT 
miltefosine 
 
Impavido 
AKT, PI3K, PKC  

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Molecular Analysis for Therapy Choice (MATCH) 
MATCH Treatment Subprotocol Y: AZD5363 in Patients with Tumors with AKT Mutations 
Appendix V 
 
Information On Possible Drug Interactions 
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 drug, AZD5363.  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.  
These are the things that you as a healthcare provider need to know: 
AZD5363 interacts with certain specific enzymes in the liver and certain transport proteins that 
help move drugs in and out of cells. 
• 
Some of the enzymes in question are UGT 1A9, 2B7 and CYP 3A4/5 and 2C9. AZD5363 is 
broken down by these enzymes and is affected by other drugs that are potent inducers or 
inhibitors of UGT 1A9, 2B7 and CYP 3A4/5 and 2C9. Avoid use of other drugs that are 
strong inducers or inhibitors of these enzymes within 2 weeks (within 3 weeks for St John’s 
Wort) of AZD5363 administration. 
• 
AZD5363 may affect other drugs by inhibiting enzymes needed to clear them from the body. 
These enzymes are UGT1A1, CYP 3A4/5 and 2D6. Avoid use of other drugs that are 
sensitive substrates of CYP 3A4/5 and 2D6 within 2 weeks of AZD5363 administration. 
• 
The transport proteins in question are OATP1B1, OATP1B3, OAT3, MATE1, MATE2K, 
OCT2 and BCRP. AZD5363 may inhibit other drugs from being moved in and out of 
cells/organs by these transport proteins. In particular, metformin and certain statins may 
interact with AZD5363 and need to be managed carefully in patients taking them 
concurrently. Inhibitors of P-gp may affect how AZD5363 is transported in and out of 
cells/organs. 
To the patient: Take this paper with you to your medical appointments and keep the 
attached information card in your wallet.   
AZD5363 may interact with other drugs which can cause side effects. For this reason, it is very 
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:  
AZD5363 must be used very carefully with other medicines that affect P-gp transporter, UGT 
1A9, 2B7 and CYP 3A4/5, 2C9 enzymes needed to clear it from your body. AZD5363 may affect 
enzymes UGT1A1, CYP 3A4/5 and 2D6 that are needed to clear other drugs from your body. 
AZD5363 inhibits OATP1B1, OATP1B3, OAT3, MATE1, MATE2K, OCT2 and BCRP transport 
proteins that may be required to move other drugs in and out of cells/organs. Before you enroll 
Rev. 12/16 
Rev. Add13 

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onto the clinical trial, your study doctor will work with your regular health care providers to 
review any medicines and herbal supplements  that are considered “strong inducers/inhibitors of 
P-gp, UGT 1A9, 2B7 and CYP 3A4/5, 2C9 or substrates of CYP 3A4/5 and 2D6 or substrates of 
transport proteins OATP1B1, OATP1B3, OAT3, MATE1, MATE2K, OCT2 and BCRP.” 
• 
Please be very careful!  Over-the-counter drugs (including herbal supplements such as St 
John’s Wort) may contain ingredients that could interact with your study drug.  Speak to your 
doctors or pharmacist to determine if there could be any side effects. 
• 
Avoid ingesting grapefruit juice, grapefruit and Seville oranges while taking AZD5363 
• 
Your regular health care provider should check a frequently updated medical reference or 
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  
_____________________________________. 
 
STUDY DRUG INFORMATION WALLET CARD   
You are enrolled on a clinical trial using the experimental 
study drug AZD5363. This clinical trial is sponsored by 
the NCI. AZD5363 may interact with drugs that are 
processed by your liver, or use certain transport proteins 
in your body.  Because of this, it is very important to: 
➢ Tell your doctors if you stop taking any medicines or if 
you start taking any new medicines. 
➢ Tell all of your health care providers (doctors, 
physician assistants, nurse practitioners, or 
pharmacists) that you are taking part in a clinical trial. 
➢ Check with your doctor or pharmacist whenever you 
need to use an over-the-counter medicine or herbal 
supplement 
AZD5363 interacts with UGT1A1, UGT1A9, 2B7 and 
CYP 3A4/5, 2C9 and 2D6 and transport proteins P-gp, 
OATP1B1, OATP1B3, OAT3, MATE1, MATE2K, OCT2 
and BCRP and must be used very carefully with other 
medicines that interact with these enzymes and transport 
proteins. 
➢ 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 are considered “strong 
inducers/inhibitors of P-gp, UGT 1A9, 2B7 and CYP 
3A4/5, 2C9 or substrates of CYP 3A4/5, 2D6 or 
substrates of transport proteins OATP1B1, 
OATP1B3, OAT3, MATE1, MATE2K, OCT2 and 
BCRP.” 
➢ Avoid ingesting grapefruit juice, grapefruit and Seville 
oranges while taking AZD5363. 
➢ Before prescribing new medicines, your regular 
health care providers should go to a frequently-
updated medical reference for a list of drugs to avoid, 
or contact your study doctor. 
Your study doctor’s name is _____________________  
and can be contacted at ________________________.