MATCH Treatment Subprotocol P: Phase II Study of PI3K Beta Specific Inhibitor, GSK2636771, in Patients With Tumors With PTEN Loss by IHC
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 
 
 
February 6, 2017 
 
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 #7 to EAY131-P, Molecular Analysis for Therapy Choice (MATCH): 
MATCH Treatment Subprotocol P: Phase II Study of PI3K Beta Specific Inhibitor, GSK2636771, 
in Patients with Tumors with PTEN Loss by IHC. 
Please note, the following revisions to this subprotocol were not originally included in the 
submission of MATCH Addendum #7, which has since been reviewed by CTEP and the CIRB. 
Per discussions with PIO, changes to this subprotocol are now incorporated along with the 
resubmission of Addendum #7 to the CIRB. For any questions related to this submission plan, 
please contact Martha Kruhm at PIO and/or Amanda Putnick at the CIRB. 
The following revisions to EAY131-P protocol have been made in this addendum: 
 
Section 
Change 
1. 
Cover Page 
Updated Version Date and added “Addendum #7” to the activation date list 
2. 
4.1 
Footnote E: Updated language for additional specimen collection 
parameters under the Master Protocol. 
Table updated with additional optional blood submission time point. 
3. 
5 
Inserted “Investigator Brochure Availability” subsection, per CTEP request, 
for consistency across subprotocols. 
4. 
Appendix I 
Added additional instructions to pill calendar directions for clarity. 
5. 
Addendum II 
Removed duplicate variant in aMOI list (COSM180789) 
6. 
Addendum III 
Updated “Patient Drug Information Handout and Wallet Card” appendix with 
new language provided by CTEP 
The following revisions to EAY131-P Informed Consent Document have been made in this 
addendum: 
 
Section 
Change 
1. 
Page 1 
Updated Version Date 
 
 
Operations Office – Boston  
 
 

ii 
2. 
“What are the study 
groups?” 
Added additional dosing instructions for consistency with the subprotocol. 
3. 
“What are the study 
groups?” 
The term “medication diary” has been replaced with the term “patient pill 
calendar” for consistency with the subprotocol. 
4. 
“What 
possible 
risks…? 
Updated contraception use from “continuing for up to 16 weeks” to 
“continuing for 16 weeks” as contraception is required for all 16 weeks after 
treatment. 
5. 
Study Calendar 
The term “medication diary” has been replaced with the term “patient pill 
calendar” throughout for consistency with the subprotocol. 
If you have any questions regarding this addendum, please contact 
zhang.jeffrey@jimmy.harvard.edu or 857-504-2900. 
We request review and approval of this addendum to EAY131-P so ECOG-ACRIN may activate 
it promptly.   
Thank you.  
Sincerely, 
 
Pamela Cogliano 
Director of Protocol Development 
Enclosure 
CC: Filip Janku, MD, PhD 
Shannon Puhalla, MD 
Panagiotis Konstantinopoulos, MD, 
PhD 
Alice Chen, MD 
Keith Thomas Flaherty, MD 
Barbara A. Conley, MD 
Peter O’Dwyer, MD 
Mickey Williams, 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 
James Zwiebel, MD 
Bruce Giantonio, MD 
Robert L. Comis, MD 
Donna Marinucci 
Kerry Higgins 
Gayle Ipock 
Jean MacDonald 
Carol Chami, R.N. 
Julianne Human 
Becky Fillingham 
Jeffrey Zhang 
Kevin Pollard 
Amy Li 
Lauren Lambert 
Ben Kim 
Margo Cavenagh 
Cayden Maican 
 

iii 
 

 
EAY131-P 
1 
Molecular Analysis for Therapy 
Choice (MATCH) 
MATCH Treatment Subprotocol P: Phase II Study of PI3K 
Beta Specific Inhibitor, GSK2636771, in Patients with 
Tumors with PTEN Loss by IHC 
GSK2636771 TREATMENT SUBPROTOCOL 
CHAIR: 
 
Filip Janku, MD, PhD 
GSK2636771 TREATMENT SUBPROTOCOL 
CO-CHAIR: 
 
Shannon Puhalla, MD 
GSK2636771 TRANSLATIONAL CHAIR: Panagiotis Konstantinopoulos,  MD, PhD 
  
Version Date:  February 6, 2017 
 
NOTE: This subprotocol (EAY131-P) should be 
used in conjunction with the MATCH 
Master Protocol (EAY131). 
 
SUBPROTOCOL ACTIVATION DATE 
February 25, 2016 (Incorporated in Addendum #2) 
Addendum #5 – 12/16 
 
 
Addendum #7 – 3/17 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Agent 
IND# 
NSC# 
Supply 
GSK2636771 
NCI Sponsor: DCTD, NCI IND #: 
 
781258 
NCI Supplied 
 

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Version Date: February 6, 2017 
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Table of Contents 
Molecular Analysis for Therapy Choice (MATCH) ...................................................... i 
MATCH Treatment Subprotocol P: Phase II Study of PI3K Beta Specific Inhibitor, 
GSK2636771, in Patients with Tumors with PTEN Loss by IHC ........................... 1 
Table of Contents ...................................................................................................... 2 
Schema ...................................................................................................................... 4 
1. Introduction ........................................................................................................ 5 
1.1 
Background ............................................................................................... 5 
1.2 
GSK2636771 .............................................................................................. 7 
1.3 
Supporting Preliminary Data ................................................................... 10 
2. Selection of Patients ......................................................................................... 11 
2.1 
Eligibility Criteria: .................................................................................... 11 
3. GSK2636771 Treatment Plan ............................................................................ 14 
3.1 
Administration Schedule ......................................................................... 14 
3.2 
Adverse Event Reporting Requirements ................................................. 14 
3.3 
Comprehensive Adverse Events and Potential Risks List (CAEPR) for 
GSK2636771 (NSC 781258) ..................................................................... 17 
3.4 
Dose Modifications ................................................................................. 19 
3.5 
Supportive Care ....................................................................................... 21 
3.6 
Duration of Agent-specific treatment ..................................................... 21 
3.7 
Duration of Follow-Up ............................................................................. 21 
4. Study Parameters .............................................................................................. 22 
4.1 
Therapeutic Parameters for GSK2636771 Treatment ............................ 22 
5. Drug Formulation and Procurement ................................................................. 24 
5.1 
GSK2636771 (NSC 781258) ..................................................................... 25 
6. Translational Studies ......................................................................................... 27 
7. References ........................................................................................................ 27 
Appendix I  Patient Pill Calendar ............................................................................. 29 
Appendix II  Excluded Mutations for Sub-Protocol EAY131-P ................................. 31 
Appendix III Patient Drug Information Handout and Wallet Card .......................... 37 
 
 
 

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TREATMENT SUBPROTOCOL CHAIR 
Filip Janku, MD, PhD, 
The University of Texas 
MD Anderson Cancer Center 
The Department of Investigational Cancer Therapeutics 
(Phase I Clinical Trials Program)  
1515 Holcombe Blvd. Houston, TX 
Phone: 713-563-0803 
Fax: 713-792-5576 
Email: FJanku@mdanderson.org 
 
TREATMENT SUBPROTOCOL CO-CHAIR 
Shannon Puhalla, MD 
The University of Pittsburgh 
Magee Womens Cancer Center  
300 Halket Street, Suite 3524 
Pittsburgh, PA 15213 
Phone:412-641-5792 
Fax: 412-641-2294 
Email: puhallasl@upmc.edu 
 
TRANSLATIONAL CHAIR 
Panagiotis Konstantinopoulos, MD, PhD 
Dana-Farber Cancer Institute 
Harvard Medical School 
Gynecologic Oncology Program 
Phone: 617-632-6232 
Fax: 617-632-3479 
Email: panagiotisa konstantinopoulos@dfci.harvard.edu 
 

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Schema 
 
 
 
Long-Term Follow-Up
GSK2636771 400mg po daily
Until Progression
Cycle = 28  days
Accrual Goal: 35

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1. 
Introduction 
1.1 
Background 
The mechanisms underlying cancer are marked by complex aberrations that 
activate critical cellular signaling pathways in tumorigenesis.  Identifying 
actionable molecular aberrations has been critical to several major therapeutic 
advances in cancer medicine. Examples include BCR-ABL fusion in chronic 
myeloid leukemia (CML), epidermal growth factor (EGFR) mutations and EML4-
ALK fusion in non-small cell lung cancer, and BRAF mutations in melanoma.1-4 
The phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of 
rapamycin (PI3K/AKT/mTOR) signaling cascade is one of the most important 
intracellular pathways, which is frequently activated in diverse cancers (Figure 
1).5,6 PI3K/AKT/mTOR signaling regulates cell proliferation, differentiation, 
cellular metabolism, and cytoskeletal reorganization leading to apoptosis and 
cancer cell survival. Activation of the PI3K/AKT/mTOR signaling pathway 
mediated through molecular aberrations such as loss of PTEN function is 
instrumental in promoting tumor development as well as resistance to anticancer 
therapies.7,8 Preclinical models and early clinical data in several tumor types 
suggested that loss of PTEN function can result in increased sensitivity to 
therapies targeting the PI3K/AKT/mTOR signaling pathway.5,9,10 It is conceivable 
that loss of PTEN function, which is a major negative regulator of the pathway, 
can be predictive, whereas simultaneous mutations in the mitogen-activated 
protein kinase (MAPK) or PI3K pathways may lead to therapeutic resistance.5,8,11-
13, 27-29 
 
The tumor suppressor gene PTEN (also known as MMAC, mutated in multiple 
advanced cancers) was initially observed independently by two groups in 1997 
on the 10q23 chromosomal region of PTEN, which was known to be deleted in 
many advanced cancers.14,15 PTEN is a lipid phosphatase that catalyzes the 
conversion of the second messenger PIP3 to PIP2 and thus reverses PI3K 
functionality in signal propagation (Figure 1).16 Moreover, it is now well 
established that PTEN has serine, threonine, and tyrosine phosphatase activity 
for several protein substrates, resulting in its complex functions in cellular 

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signaling.17 PTEN protein consists of 403 amino acids divided into functional 
domains, the N-terminal PIP2-binding domain (PBD), phosphatase domain, C2 
domain and C-terminal tail with two PEST (proline, glutamic acid, serine, 
threonine) domains, and a sequence governing protein-protein interactions 
(PDZ).18 These different PTEN domains are relevant to its tumor suppressor 
function due to the large diversity of tumor-associated mutations observed across 
all of its domains.19 The loss of PTEN function can be caused by various 
mechanisms including mutations, deletions, transcriptional silencing and 
epigenetic changes.20 Transcriptional repression and epigenetic silencing of 
PTEN typically occurs via gene promoter hypermethylation.21,22  
Mutations as well as loss of PTEN are found in various tumor types. The TCGA 
studies identified PTEN mutations in 63% of endometrial cancers, 30% of 
glioblastomas, 8% of cervical cancers, 7% of skin cancers as well as in other 
tumor types (cBioPortal for Cancer Genomics). The COSMIC database identified 
PTEN mutations in 39% of endometrial cancers, 14% of central nervous system 
tumors, 12% of skin cancers, 11% of colorectal cancers, 10% of prostate 
cancers, 5% of cervical cancers as well as in other tumor types (Figure 2) 
(COSMIC [Catalogue of Somatic Mutations in Cancer]). The complete loss of 
PTEN was also observed in a high number of cases of uterine (33%), renal 
(27%), salivary gland (20%), colorectal (18%), breast (13%), pancreatobiliary 
(13%) and prostate cancers (11%).23 Because of the numerous mechanisms 
underlying PTEN inactivation on genetic and epigenetic levels, accurate 
assessment of PTEN status in individual tumor samples remains challenging. 
 
Preclinical models demonstrated that PTEN function is an important regulator of 
G protein-coupled receptor signaling transmitted through PIK3CB. PTEN-
deficient tumors are critically dependent on PIK3CB activity and tumors with 
PIK3CB activation are sensitive to PIK3CB inhibitors.10,24 Notably, breast cancer 
cell lines with PTEN loss compared to those with PIK3CA mutations 
demonstrated resistance to treatment with mTOR complex 1 (mTORC1) targeted 
therapy.9 A complete loss of PTEN expression was found in 10% of heavily 
pretreated patients with diverse advanced solid tumors, and 23% of them 
experienced a partial response or stable disease greater than or equal to 6 
months when treated with a PI3K/AKT/mTOR axis inhibitors.23 These findings 

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suggest that matching patients with inhibitors based on PTEN aberrations merits 
further exploration.5  
GSK2636771 is a potent and selective inhibitor of phosphoinositide 3-kinase 
(PI3K) beta, which demonstrated activity in preclinical models with a loss of 
PTEN function.25 In addition, the first-in-human dose escalation study has been 
completed.25 Because PTEN function could be lost in various ways as noted 
above, MATCH will examine patients with complete PTEN loss of expression (by 
IHC) as well as those who retain PTEN expression by IHC but have a PTEN 
mutation or deletion by NGS. In the context of the NCI MATCH protocol, this is a 
phase II open label study for patients with PTEN deficient tumor (complete loss 
of staining on IHC with or without PTEN mutation or deletion). A separate 
MATCH subprotocol (EAY131-N) will investigate PTEN mutations without loss of 
IHC expression of PTEN. 
1.2 
GSK2636771 
1.2.1 
Non-clinical and clinical data 
GSK2636771 has been assessed in primary and secondary 
pharmacodynamic studies, as well as safety, pharmacology and 
toxicology studies. A summary of the available relevant non-clinical 
data is provided below. Study details and additional information can 
be found in the Investigator Brochure.  
1.2.2 
Non-clinical pharmacology 
GSK2636771 is a potent and selective inhibitor of phosphoinositide 3-
kinase (PI3K) beta with an apparent Ki (Kiapp) value of 0.89 nM with 
selectivity > 900-fold over PI3K alpha and gamma with Kiapp values 
of 819 and > 5000 nM, respectively, and 10-fold over PI3K delta 
(Kiapp of 8.6 nM). Among the other members of the PI3K superfamily 
tested, GSK2636771 was not inhibitory at concentrations > 10uM and 
demonstrated less than 30% inhibition against 294 additional kinases. 
GSK2636771 is an ATP competitive inhibitor of PI3K beta that is 
rapidly reversible and not time dependent and has a similar potency 
(within 2-fold) against three PI3K beta orthologs; mouse, rat and dog 
as compared to human PI3K beta.  
In phosphatase and tensin homolog (PTEN) mutant cell lines, but not 
wild-type PTEN lines, GSK2636771 inhibited cellular AKT 
phosphorylation in a concentration dependent manner. In the cell lines 
evaluated, the inhibition of AKT phosphorylation resulted in the 
inhibition of downstream PI3K/AKT signalling molecules in PTEN 
deficient, but not PTEN wild-type cell lines. GSK2636771 inhibited the 
anchorage independent cell growth of 87% of PTEN null tumor cell 
lines (13 out of 15 cell lines) but only 14% of PTEN wild-type (1 out of 
7).  
In mice bearing PC3 prostate carcinoma xenografts, single oral daily 
doses of GSK2636771 at 10, 30 and 100 mg/kg for 21 days resulted 
in stable disease with minimal tumor growth delay at 1 and 3 mg/kg. 
In mice bearing PC3 prostate carcinoma or HCC70 breast carcinoma 
xenografts, oral doses of 3 or 10 mg/kg (PC-3) or 10 or 30 mg/kg 
(HCC70) GSK2636771 inhibited AKT phosphorylation in both tumor 

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Version Date: February 6, 2017 
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types (by up to 80%), in a dose-dependent manner. Inhibition of AKT 
phosphorylation was rapid and lasted for several hours after a single 
oral administration. In naïve mice, single oral daily doses of 100 
mg/kg GSK2636771 for four consecutive days did not affect fasting 
blood glucose and insulin levels. GSK2636771 showed significant 
anti-tumor activities in a PDX model of gastric cancer when 
administered alone or in combination with trametinib (GSK1120212, a 
potent and selective MEK inhibitor). In a combined cardiovascular, 
respiratory and neurobehavioral study in dogs, a single oral dose of 
300 mg/kg produced a reversible increase in mean arterial pressure 
(up to 11 mm Hg; up to 10%) from 2 to 8 hours post dose with a 
compensatory decrease in heart rate (up to 11 bpm; up to 12%) and 
decrease in cardiac contractility (up to 4.1% increase QA interval) 
during the same time period. The decrease in heart rate appears to be 
a baroreceptor-mediated reflex response to the increased arterial 
blood pressure, while the decrease in the measure of contractility may 
be attributed to the decrease in heart rate and a baroreceptor-
mediated change in autonomic nervous input into the heart. Doses of 
5 or 100 mg/kg did not produce any effect on arterial pressures or 
heart rate, and repeat doses up to 1000 mg/kg/day for 1 month did not 
produce any adverse effects on electrocardiogram (ECG) 
measurements. GSK2636771 did not produce acute neurobehavioral 
or respiratory effects in dogs following single doses up to 300 mg/kg. 
GSK2636771 minimally inhibited hERG tail current at the limit of 
solubility (20% inhibition at 70 ug/mL; 161 uM). In a rabbit left 
ventricular wedge assay, GSK2636771 exerted no torsadogenic 
potential up to the maximum concentration tested (13 ug/mL; 30 uM). 
Based on the weak hERG inhibition, absence of in vitro and in vivo 
effects on QTc and the high plasma protein binding in humans (99%), 
risk for QTc prolongation in humans is predicted to be low. 
1.2.3 
Non-clinical pharmacokinetics 
The pharmacokinetics and metabolism of GSK2636771 have been 
evaluated both in vitro and in vivo in several preclinical species. 
GSK2636771 exhibited moderate blood clearance in the mouse and 
rat (32 and 47% liver blood flow, respectively), but low in the dog and 
monkey (9 and 2% liver blood flow, respectively). The steady state 
volume of distribution (Vdss) was approximately three to four times 
larger than total body water in rats and mice, suggesting the potential 
for tissue distribution. However, in dogs and monkeys, the Vdss was 
equivalent to, or less than total body water. The half-life (t1/2) ranged 
from 1.37 to 5.88 hours. The oral bioavailability of GSK2636771 was 
high (≥ 94%). Protein binding was species dependent with the highest 
free fraction in mouse (35%) and the lowest free fraction in human 
(1.3%). GSK2636771 has high passive membrane permeability and 
was not a substrate for P-glycoprotein (Pgp). GSK2636771 appeared 
to minimally distribute to the brain in the rat (brain concentration was 
7% of blood concentration following a 1 hour intravenous infusion of 2 
mg/kg). 
GSK2363771 had low intrinsic clearance in hepatic microsomes and 
hepatocytes of all species evaluated (i.e. rat, dog and human). In vitro 

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and in vivo (rat), acyl glucuronidation was the major metabolic route 
for GSK2636771. However, GSK2636771 was the only detected 
component in rat blood. The major route of elimination in the rat was 
via the feces. The absorbed dose was eliminated primarily in the bile 
(the acyl glucuronide metabolite was the major component). 
GSK2636771 did not inhibit the major drug metabolizing cytochrome 
P450 (CYP450) enzymes including CYP3A4, and was not a time or 
metabolism dependent inhibitor of CYP3A4. GSK2636771 did not 
inhibit the drug transporters Pgp, breast cancer resistance protein 
(BCRP), organic anion transport polypeptide (OATP) 1B1 or 
OATP1B3. Therefore, the risk of GSK2636771 functioning as a 
perpetrator of drug interactions appears low. 
1.2.4 
Non-clinical toxicology and safety pharmacology 
The systemic toxicity of GSK2636771 has been evaluated in rats and 
dogs. Genotoxicity studies have also been conducted. The principal 
dose-limiting toxicities seen in animal toxicology studies conducted 
with GSK2636771 were kidney and gastrointestinal effects. There was 
a dose dependent increase in kidney tubular basophilia at ≥100 
mg/kg/day in rats with single cell and/or tubular necrosis in rats at 
1000 mg/kg/day and tubular degeneration/regeneration in dogs at 
1000 mg/kg/day. In rats, these findings correlated with increased 
mean kidney weights, decreased serum potassium, and increased 
mean serum urea. Urinary markers of kidney injury increased in rats 
and included KM1C, lipocalin-2, clusterin, RPAC at ≥100 mg/kg/day 
and urinary albumin, total protein, NAG, osteopontin, and alpha GST 
at 1000 mg/kg/day. Decreased body weight gain and food 
consumption and focal erosion and ulceration occurred in rat 
stomachs at 1000 mg/kg/day. The increased WBC counts in female 
rats at 1000 mg/kg/day is likely related to inflammation due to the 
kidney and gastrointestinal lesions. Increased heart weight and 
intramural coronary artery hypertrophy without ECG effects were 
observed in 1 male dog given 1000 mg/kg/day. A single dose of 300 
mg/kg produced a reversible increase in mean arterial pressure, 
decreased heart rate and decreased cardiac contractility. Additional 
adverse findings in animals given 1000 mg/kg/day were present in 
liver, stomach, hematopoietic and reproductive systems. In dogs, 
there was minimal to mild single cell hepatocellular necrosis with 
increased serum ALT, GLDH and AST. Lymphoid necrosis occurred 
in spleen, lymph nodes, and GALT of dogs, and rats had decreased 
thymus weights. Spermatocyte depletion was observed in rats (also at 
100 mg/kg/day) and dogs. In general, these findings were consistent 
with the expression and function of PI3 kinase. Based on the weak 
hERG inhibition, absence of in vitro and in vivo effects on QTc and the 
high plasma protein binding in humans (99%), the risk for QTc 
prolongation in humans is predicted to be low. In addition, 
GSK2636771 has a low genotoxic risk to humans. The kidney, 
gastrointestinal and liver effects are clinically monitorable and 
manageable, and generally recovered within 2 weeks off-treatment. In 
the 4 week rat study, the no observed adverse effect level (NOAEL) 
was 10 mg/kg/day [gender averaged AUC0-t 7.08 ug.h/mL, Cmax 
1.83 ug/mL, Day 28 values]. The NOAEL in the 4 week dog study was 

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Version Date: February 6, 2017 
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100 mg/kg/day [gender averaged AUC0-t 225 ug.h/mL, Cmax 38.8 
ug/mL, Day 28 values]. 
1.3 
Supporting Preliminary Data  
1.3.1 
Clinical Data 
To date, the administration of GSK2636771 has been limited to 53 
subjects with PTEN deficient tumors as determined by 
immunohistochemistry (IHC) analysis who were enrolled in the FIM 
study P3B115717.25 The dose escalation part of the study has 
completed, and is now in an expansion phase enrolling patients with 
several tumor types with PTEN deficiency. Doses of GSK2636771 
evaluated have ranged from 25 mg to 500 mg once daily. The 
maximum tolerated dose (MTD) has been defined as 400 mg orally 
once daily.  
1.3.2 
Safety 
Dose limiting toxicities (DLTs) observed were hypophosphatemia and 
hypocalcemia. Dose-limiting toxicity (DLT) of hypophosphatemia was 
identified at 500 mg daily dose level, occurring in 3 of 4 subjects, and 
resulting in dose reductions and or discontinuations. 
Hypophosphatemia improved upon discontinuation of GSK2636771. 
The mechanism(s) of hypophosphatemia is under investigation. The 
most frequent adverse events (AEs) with GSK2636771 were Grade 1 
or Grade 2 gastrointestinal (GI) toxicities, with the most frequently 
reported AEs being diarrhea (43%), nausea (43%), fatigue (28%), 
vomiting (34%), abdominal pain (26%), decreased appetite (23%), 
anemia (23%), constipation (19%), headache (17%), hypokalemia 
(15%), Rash (15%), cough (13%), dyspnea (11%), edema peripheral 
(13%), hypocalcemia (13%), hypophosphatemia (11%), and urinary 
tract infection (13%). 
1.3.3 
Pharmacokinetics 
Preliminary pharmacokinetics (PK) results from study P3B115717 
indicate that GSK2636771 is absorbed orally with a median time to 
achieve the peak blood concentration (tmax) of 4 to 5 hrs after single 
doses of 25 to 500 mg. The median half-life of GSK2636771 ranged 
from 17.1 to 38.6 hrs across the dose range of 25 mg to 500 mg once 
daily. Mean maximum observed concentration (Cmax) and area under 
the concentration-time curve from zero (pre-dose) to 24 hrs (AUC(0-
24)) values on Day 22 were greater than the mean values observed 
after a single dose, demonstrating that GSK2636771 accumulated in 
plasma after repeated doses. 
1.3.4 
Efficacy 
There are limited data available to assess the clinical activity of 
GSK2636771. In the FTIH study P3B115717 in patients with PTEN 
loss as determined by IHC, one subject with mCRPC who received 
200 mg GSK2636771 once daily had a partial response (PR) per 
RECIST. There were 16 subjects (with various solid tumors) with 
stable disease and 8 subjects (with various solid tumors) who 
continued treatment for at least 6 months. 

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2. 
Selection of Patients 
Each of the criteria in the checklist that follows must be met, along with the eligibility in 
the MATCH Master Protocol, in order for a patient to be considered eligible for this 
study. Use the checklist to confirm a patient’s eligibility. For each patient, this checklist 
must be photocopied, completed and maintained in the patient’s chart.  
In calculating days of tests and measurements, the day a test or measurement is 
done is considered Day 0. Therefore, if a test is done on a Monday, the Monday 
four weeks later would be considered Day 28.  
ECOG-ACRIN Patient No. ____________________________ 
Patient’s Initials (L, F, M) _______________________ 
Physician Signature and Date ___________________ 
NOTE: 
Policy does not allow for the issuance of waivers to any protocol specified 
criteria (http://ctep.cancer.gov/protocolDevelopment/policies deviations.htm). 
Therefore, all eligibility criteria listed in Section 2 must be met, without 
exception. The registration of individuals who do not meet all criteria listed in 
Section 2 can result in the participant being censored from the analysis of the 
study, and the citation of a major protocol violation during an audit.  All 
questions regarding clarification of eligibility criteria must be directed to the 
Group's Executive Officer (EA.Execofficer@jimmy.harvard.edu) or the 
Group's Regulatory Officer (EA.RegOfficer@jimmy.harvard.edu). 
NOTE: 
Institutions may use the eligibility checklist as source documentation if it has 
been reviewed, signed, and dated prior to registration/randomization by the 
treating physician. 
NOTE: 
All patients must have signed the relevant treatment consent form 
2.1 
Eligibility Criteria: 
Patients must meet all of the following 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 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:  _______________ 
2.1.3 
Patients must not have known hypersensitivity to GSK2636771 or 
compounds of similar chemical or biologic composition. 
2.1.4 
Patients must have complete loss of cytoplasmic and nuclear PTEN 
staining on immunohistochemistry as determined by the MATCH 
PTEN IHC assay performed at MD Anderson. Patients can have any 
PTEN mutation or deletion status, but MUST have PTEN loss by IHC.   
2.1.5 
Patients must not have tumors harboring co-existing aberrations 
activating the PI3K/MTOR and MAPK pathways, such as PIK3CA, 
_____
Rev. 12/16 

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PIK3R1, BRAF, KRAS and AKT1, TSC1/2, mTOR, NF2, NRAS, 
HRAS, NF1 (See Appendix II for exclusion mutations and 
corresponding Levels of Evidence). 
2.1.6 
Patients must not have received prior treatment with agents targeting 
the PI3K beta, AKT, or mTOR: 
2.1.6.1 
This includes (but is not limited to): 
i. 
mTOR inhibitors: temsirolimus, everolimus, 
ridaforolimus, sirolimus, salirasib, CC-223, INK128, 
DS-3078, CC-115, AZD-2014 
ii. dual PI3K/mTOR inhibitors: BEZ235, XL-765, GDC 
0980, PF-04691502, GSK 2126458, Quinacrine, PKI-
587, P-P7170, LY3023414, GDC 0084, DS 7423, 
CBLC-137 
iii. pan-PI3K inhibitors: BKM-120 (buparlisib), PX-866, XL-
147, GDC-0941 (pictilisib), BAY-806946, ZSTK-474, 
WX 037, SRX5000, SRX2523, AMG511, PQR308, 
BAY 94-9343 
iv. PI3K inhibitors with β isoform activity: prior 
GSK2636771 is not allowed, nor is GS-9820, PQR3XX, 
KAR4139 
2.1.6.2 
The following previous treatments are allowed: 
i. 
BYL719 (PI3Kα inhibitor)  
ii. GDC-0032 (PI3Kαinhibitor) 
iii. INK1117 (PI3Kα inhibitor) 
iv. Idelalisib (PI3Kδ inhibitor) 
v. IPI-125 (PI3K γδ inhibitor) 
vi. TGR1202 (PI3Kδ inhibitor) 
vii. SRX2558 (PI3Kδ inhibitor) 
viii. RP6530 (PI3K γδ inhibitor) 
ix. PWT143 (PI3Kδ inhibitor) 
x. IPI443 (PI3K γδ inhibitor) 
xi. GNE293 (PI3Kδ inhibitor) 
2.1.7 
Patients with a history of interstitial lung disease or pneumonitis are 
excluded. 
2.1.8 
Patients must have hemoglobin ≥ 9 g/dL. 
2.1.9 
Patients must have a serum creatinine that is < 1.5 x ULN or have a 
24-hour creatinine clearance of > 50 mL/min.  

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2.1.10 
Patients must not have any congenital platelet function defects and 
cannot be on any of the following anti-platelet drugs: clopidogrel, 
ticlopidine, prasugrel, that act at platelet purinergic receptors. 
2.1.10.1 
Any need for starting anti-platelet therapy in a patient 
enrolled to this arm will have to be evaluated by the 
subprotocol chair. 
 
 
 
 
 
Physician Signature 
 
Date 
OPTIONAL: 
This signature line is provided for use by institutions wishing to 
use the eligibility checklist as source documentation. 
 
 

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3. 
GSK2636771 Treatment Plan 
3.1 
Administration Schedule 
GSK2636771 will be administered on an oral, daily, continuous administration 
schedule. The starting dose of the drug will be 400mg (four 100 mg capsules), 
once daily, which was deemed the maximum tolerated phase II dose from the 
company sponsored phase I study.  
Each cycle of therapy will be 28 days and there will not be any breaks between 
dosing cycles. Patients must meet the following criteria in order to proceed with 
the next cycle of treatment: 
• 
ANC ≥ 1,000/μL 
• 
Platelets ≥ 75,000/μL 
• 
Hemoglobin ≥ 9 g/dL 
• 
Phosphorous, magnesium, potassium, and calcium (corrected for albumin) 
must either be within normal range for labs or no worse than grade 2. 
Supplementations may be used to keep within these ranges.  
• 
Serum creatinine must be ≤ 1.5 x ULN or 24-hour creatinine clearance of  
≥ 50 mL/min.  
Please refer to Section 3.4 for dose modifications. Within cycle toxicity that meets 
grade 3 or 4 criteria, will necessitate holding of the drug until the toxicity are 
improved to grade 1 or baseline, unless otherwise specified in the protocol. 
Repeat cycles until progression. 
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 EAY131 – 
Subprotocol P  
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. 
 
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EAY131 – Subprotocol P 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 
GSK2636771 or within 28 days of the subject’s last dose of 
GSK2636771, 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 P specific expedited reporting 
exceptions: 
For Subprotocol P, 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. 
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  

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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. 

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PIO@CTEP.NCI.NIH.GOV. Your name, the name of the investigator, the protocol and the agent should 
be included in the e-mail. 
Adverse events reported on GSK2636771 trials but for which there is insufficient 
evidence to suggest that there was a reasonable possibility that GSK2636771 caused the 
adverse event: 
GASTROINTESTINAL DISORDERS - Constipation; Dry mouth; Mucositis oral; Small intestinal 
obstruction 
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS - Fever; General 
disorders and administration site conditions - Other (mucosal inflammation); Pain 
INFECTIONS AND INFESTATIONS - Upper respiratory infection 
INVESTIGATIONS - Alanine aminotransferase increased; GGT increased; Investigations - 
Other (N-terminal prohormone brain natriuretic peptide increased); Neutrophil count decreased 
METABOLISM AND NUTRITION DISORDERS - Hypoalbuminemia; Hypokalemia; 
Hypomagnesemia 
PSYCHIATRIC DISORDERS - Depression; Insomnia 
RENAL AND URINARY DISORDERS - Proteinuria; Urinary retention 
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS - Dyspnea; Productive cough 
VASCULAR DISORDERS - Hypertension 
Animal Data: The following toxicities have been observed in animal studies with 
GSK2636771: 
Dogs 
HEPATOBILIARY DISORDERS - Single cell hepatocellular necrosis with perivascular mixed 
inflammatory cell infiltrate; pigmented macrophages and kupffer cells 
IMMUNE SYSTEM DISORDERS - Lymphoid necrosis (spleen, lymph node, GALT) 
INVESTIGATIONS - Increased glutamate dehydrogenase (GLDH) 
RENAL AND URINARY DISORDERS - Tubular degeneration/regeneration 
REPRODUCTIVE SYSTEM AND BREAST DISORDERS - Seminiferous tubular depletion 
Rats 
BLOOD AND LYMPHATIC SYSTEM DISORDERS - Leukocytosis 
GASTROINTESTINAL DISORDERS - Focal erosions and/or erosion/ulcer and mucous cell 
hypertrophy in glandular region 
IMMUNE SYSTEM DISORDERS - Decreased thymus weight 
INVESTIGATIONS - Increased serum urea; weight loss 
RENAL AND URINARY DISORDERS - Hyaline droplets in cortical proximal tubule; increased 
kidney weight; increased urinary biomarkers; inflammatory cell infiltrate in cortex; necrosis of 
cortical tubules; tubular basophilia 
REPRODUCTIVE SYSTEM AND BREAST DISORDERS - Decreased testis weight; reddened 
ovarian cysts; spermatid retention; spermatocyte depletion 
NOTE: 
GSK2636771 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). 
GSK2636771 will be administered on an oral, daily, continuous administration 
schedule. The starting dose of the drug will be 400mg (four 100 mg capsules), 
once daily which was deemed the maximum tolerated phase II dose from the 
company sponsored phase I study.  
Each cycle of therapy will be 28 days and there will not be any scheduled breaks 
between dosing cycles. Patients must meet the following criteria in order to 
proceed with the next cycle of treatment: 
• 
ANC ≥ 1,000/μL 
• 
Platelets ≥ 75,000/μL 
• 
Hemoglobin ≥ 9 g/dL 
• 
Phosphorous, magnesium, potassium, and calcium (corrected for albumin) 
must either be within normal range for labs or no worse than grade 2. 
Supplementations may be used to keep within these ranges.  
• 
Serum creatinine must be ≤ 1.5 x ULN or 24-hour creatinine clearance of  
≥ 50 mL/min.  
At the beginning of a cycle, patients experiencing any toxicity that meets 
definition of grade 3 or 4 toxicity will have the study drug held until resolution of 
symptoms to grade 1 or baseline, unless otherwise specified in the protocol. 
Within cycle toxicity that meets grade 3 or 4 criteria, will necessitate holding of 
the drug until the toxicity are improved to grade 1 or baseline, unless otherwise 
specified in the protocol. In general, except as directed for specific examples in 
the following tables, if there is need to interrupt dosing for grade 3/4 toxicity, then 
there will be a dose reduction as per the table below, once toxicity improved to 
grade 1 or baseline. Dose may be suspended for up to 2 weeks due to toxicity. If 
treatment held for laboratory abnormality; recheck labs in one week. 
GSK2636771 will not be re-escalated once dose reduced. 
For diarrhea, nausea and vomiting, optimal supportive care should be initiated 
prior to dose reduction. If symptoms persist despite maximal supportive care, or 
at investigator discretion, doses may be reduced per criteria below. Suspend 
GSK2636771 for grade 3 or 4 symptoms and hold until resolved to grade 1 or 
baseline, unless otherwise specified in the protocol. 
Dose Reduction Table: 
Dose levels and dose reductions: 
GSK2636771 dose 
Starting dose level 
400 mg po daily 
Dose level -1 
300 mg po daily 
Dose level -2 
200 mg po daily 
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Renal Insufficiency/ Creatinine Increased:  
Toxicity grade 
Action 
Dose modification 
Subsequent occurrences 
Grade 1 
Continue with current dose 
none 
none 
Grade 2 
Hold until grade 1 
Reduce one dose level 
2nd occurrence: reduce 
additional dose level 
3rd occurrence: discontinue 
GSK2636771 
Grade 3 
Hold until grade 1 
Reduce one dose level 
2nd occurrence: reduce 
additional dose level 
3rd occurrence: discontinue 
GSK2636771 
Grade 4 
Hold until grade 1 
Reduce two dose levels 
2nd occurrence: discontinue 
GSK2636771 
Neutropenia: 
Toxicity grade 
Action 
Dose modification 
Subsequent occurrences 
Grade 1 or 2 
None 
Maintain current dose level 
 
Grade 3 
Hold GSK2636771  
until grade 2 
None 
Reduce one dose level 
Grade 4 
Hold GSK2636771  
until grade 2 
Reduce one dose level 
Reduce one dose level 
Thrombocytopenia: 
Toxicity grade 
Action 
Dose Modification 
Subsequent Occurrences 
Grade 1 
None 
Maintain current dose level 
None 
Grade 2 
Hold until grade 1 
Maintain current dose level 
Reduce one dose level 
Grade 3 
Hold until grade 1 
Reduce one dose level 
Reduce one dose level 
Grade 4 
Hold until grade 1 
Reduce one dose level 
Reduce one dose level 
Liver Function Tests (bilirubin, AST and ALT): 
Toxicity grade 
Action 
Dose modification 
Subsequent occurrences 
Grade 1 
None 
Maintain current dose level 
 
Grade 2 
None 
Maintain current dose level 
 
Grade 3 
Hold until grade 1 
Reduce one dose level 
Reduce one dose level 
Grade 4 
Hold until grade 1 
Reduce one dose level 
Reduce one dose level 

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Hypophosphatemia: 
Toxicity grade 
Action 
Dose modification 
Subsequent occurrences 
Grade 1: 
< LLN-2.5 mg/dL 
Continue with current dose 
None 
None 
Grade 2: 
< 2.5-2.0 mg/dL 
Replace phosphorous per 
institutional guidelines 
Maintain current dose 
level 
2nd occurrence: reduce 
additional dose level 
3rd occurrence: discontinue 
GSK2636771 
Grade 3: 
< 2.0-1.0 mg/dL 
Replace phosphorous per 
institutional guidelines, hold 
until grade 1 
Reduce one dose 
level 
2nd occurrence: reduce 
additional dose level 
3rd occurrence: discontinue 
GSK2636771 
Grade 4: 
< 1.0 mg/dL 
Replace phosphorous per 
institutional guidelines, hold 
until grade 1 
Reduce one dose 
level 
2nd occurrence: reduce 
additional dose level 
3rd occurrence: discontinue 
GSK2636771 
3.5 
Supportive Care  
All supportive measures consistent with optimal patient care will be given 
throughout the study. 
Diarrhea, nausea and vomiting have all been reported with GSK2636771. 
Supportive measures with anti-diarrheals and anti-emetics are recommended per 
investigator discretion or local institutional guidelines for emergence of treatment 
related symptoms.  
GSK2636771 may enhance anti-platelet activity of agents that are irreversible or 
that act through platelet purinergic receptors. Any need for starting anti-platelet 
therapy in a patient enrolled to this arm will have to be evaluated by the 
subprotocol chair. Although aspirin does not act at the purinergic receptor, 
caution is recommended when GSK2636771 and aspirin are used concomitantly. 
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:: 
• 
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 GSK2636771 Treatment 
NOTE: 
In addition to the study parameters listed in the MATCH Master Protocol, the below parameters must also be 
performed for patients receiving GSK2636771 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 
Every 2 Cycles 
H&P, Weight, Vital signsA 
X 
 XJ 
 
 
X 
Performance status 
X 
 XJ 
 
 
X 
CBC w/diff, pltsB 
X 
 XJ 
 
 
X 
Serum chemistryB 
X 
 XJ 
 
 
X 
Radiologic evaluationD 
X 
 
 XD 
 
 XF 
-HCGC 
X 
 
 
 
 
Toxicity AssessmentG 
 
X 
 
X 
 XF 
Pill Count/DiaryH 
 
X 
 
X 
 
ECGK 
X 
 XI 
 
 
 
Urinalysis 
XI 
XI 
 
 
 
Tumor biopsy and blood sample submission for 
MATCH Master ProtocolE 
 
 
X 
 X 
 
A. History and physical, including vital signs and weight at the start of each cycle (up to 3 days before start of new cycle). 
B. 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).  CBC with 
differential will be performed more frequently in patients with grade 4 neutropenia or thrombocytopenia until resolution to ≤ grade 3. CBC and 
serum chemistries are only required in follow-up until values return to pre-treatment levels or until progressive disease. 
C. Blood pregnancy test (women of childbearing potential) required prior to beginning treatment. 
D. 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 
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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. 
E. Additional blood specimens and/or biopsies are to be submitted from consenting patients per 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.  See Section 9.3.2.3 of MATCH Master Protocol. 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. 
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. 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. 
H. 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. 
I. As clinically indicated. 
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 timepoint: H&P, Weight, 
Vital Signs; Performance Status; CBC w/diff, plts; Serum chemistry; Concomitant Medications. 
K. Within 8 weeks of treatment assignment. 

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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 the Principal Investigator (or 
their authorized designees) 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 responsible investigator at each participating institution must 
be registered with CTEP, DCTD through an annual submission of FDA Form 1572 
(Statement of Investigator), Curriculum Vitae, Supplemental Investigator Data Form 
(IDF), 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. 
Active CTEP-registered investigators and investigator-designated shipping designees 
and ordering designees can submit agent requests through the PMB Online Agent Order 
Processing (OAOP) application (https://eapps-ctep.nci.nih.gov/OAOP/pages/login.jspx).  
Access to OAOP requires the establishment of a CTEP Identity and Access 
Management (IAM) account (https://eapps-ctep.nci.nih.gov/iam/) and the maintenance of 
an “active” account status and a “current” password..  
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 and a “current” password.  Questions about IB 
access may be directed to the PMB IB coordinator at IBCoordinator@mail.nih.gov 
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5.1 
GSK2636771 (NSC 781258) 
5.1.1 
Other Names: 
GSK2636771B where B denotes the tris (hydroxymethyl) 
aminomethane salt 
5.1.2 
Classification: 
Phosphoinositide 3-kinase beta (PI3Kβ) inhibitor 
5.1.3 
Mode of Action: 
GSK2636771 is a potent, orally bioavailable, adenosine triphosphate 
(ATP) competitive, selective inhibitor of phosphoinositide 3-kinase 
beta (PI3Kβ).  
5.1.4 
Storage and Stability: 
Storage: Store at room temperature up to 30° C (86° F). 
Stability: Shelf life studies are ongoing. If needed, sites may 
repackage capsules in pharmacy bottles and assign a 30-day 
expiration date. 
If a storage temperature excursion is identified, promptly return 
GSK2636771 to room temperature 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. 
5.1.5 
Dose Specifics: 
GSK2636771 will be supplied in 100mg capsules. Starting dose will 
be 400 mg (4 x 100mg capsules) once daily for 28 days per cycle. 
Dose reductions will be to 300mg and 200mg. 
5.1.6 
Preparation: 
GlaxoSmithKline supplies and the PMB/CTEP/DCTD distributes 
GSK2636771 as size 0, opaque pink 100 mg capsules (free acid 
equivalent). Excipients include microcrystalline cellulose, 
croscarmellose sodium and sodium stearyl fumarate. The capsule 
shell contains gelatin, titanium dioxide (E171) and red iron oxide 
(E172)). 
Capsules are packaged in high density polyethylene bottles with 
induction seal liners and child-resistant caps. Each bottle contains 35 
capsules. 
5.1.7 
Route of Administration: 
Oral. Take at least 1 hour before or 2 hours after a meal with 200 mL 
water (about 7 ounces). 
5.1.8 
Incompatibilities: 
GSK2636711 is highly protein bound (99%) in humans. Use caution in 
patients who are receiving concomitant medications that are also 
highly protein-bound. 
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In vitro studies demonstrate that GSK2636711 is not a substrate for 
CYP450 enzymes or efflux transporter, P-glycoprotein (P-gp). It is 
primarily eliminated by acyl glucuronidation via unspecified UGT 
isozymes. Potent inhibitors and inducers of UGT may alter 
GSK2636711 exposure.  
Studies conducted in vitro show that GSK2636711 is not an inhibitor 
of CYP 450 enzymes or an inhibitor of transporters P-gp, breast 
cancer resistant protein (BCRP) and OATP1B1 and OATP1B3. 
GSK2636771 is a weak in vitro inhibitor of OAT1, OAT3 and OCT2; 
however, the interaction risk appears to be low at clinical 
concentrations. 
In vitro studies show that GSK2636711 does not activate the 
pregnane X receptor (PXR) and theoretically has a low potential to 
induce CYP450 isozymes. 
5.1.9 
Side Effects: 
See CAEPR in Section 3.3  
5.1.10 
Nursing/Patient Implications: 
GSK2636771 may enhance antiplatelet activity of agents that are 
irreversible (aspirin) or that act through platelet purinergic receptors 
(e.g. clopidogrel, ticlopidine, prasugrel). Avoid concomitant use of 
GSK2636771 in patients taking these anti-platelet agents or in 
patients who have a history of congenital platelet function defects. 
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6. 
Translational Studies 
Please refer to the MATCH Master Protocol for information on the Translational Studies.  
7. 
References 
1. 
Druker BJ, Talpaz M, Resta DJ, et al: Efficacy and safety of a specific inhibitor of 
the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 
344:1031-7, 2001 
2. 
Lynch TJ, Bell DW, Sordella R, et al: Activating mutations in the epidermal growth 
factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. 
N Engl J Med 350:2129-39, 2004 
3. 
Flaherty KT, Puzanov I, Kim KB, et al: Inhibition of mutated, activated BRAF in 
metastatic melanoma. N Engl J Med 363:809-19, 2010 
4. 
Falchook GS, Long GV, Kurzrock R, et al: Dabrafenib in patients with melanoma, 
untreated brain metastases, and other solid tumours: a phase 1 dose-escalation 
trial. Lancet 379:1893-901, 2012 
5. 
Janku F, Hong DS, Fu S, et al: Assessing PIK3CA and PTEN in Early-Phase Trials 
with PI3K/AKT/mTOR Inhibitors. Cell Rep 6:377-87, 2014 
6. 
Liu P, Cheng H, Roberts TM, et al: Targeting the phosphoinositide 3-kinase 
pathway in cancer. Nat Rev Drug Discov 8:627-44, 2009 
7. 
Hollander MC, Blumenthal GM, Dennis PA: PTEN loss in the continuum of 
common cancers, rare syndromes and mouse models. Nat Rev Cancer 11:289-
301, 2011 
8. 
Engelman JA, Chen L, Tan X, et al: Effective use of PI3K and MEK inhibitors to 
treat mutant Kras G12D and PIK3CA H1047R murine lung cancers. Nat Med 
14:1351-6, 2008 
9. 
Weigelt B, Warne PH, Downward J: PIK3CA mutation, but not PTEN loss of 
function, determines the sensitivity of breast cancer cells to mTOR inhibitory drugs. 
Oncogene 30:3222-33, 2011 
10. Ni J, Liu Q, Xie S, et al: Functional Characterization of an Isoform-Selective 
Inhibitor of PI3K-p110beta as a Potential Anticancer Agent. Cancer Discov 2:425-
33, 2012 
11. Ihle NT, Lemos R, Jr., Wipf P, et al: Mutations in the phosphatidylinositol-3-kinase 
pathway predict for antitumor activity of the inhibitor PX-866 whereas oncogenic 
Ras is a dominant predictor for resistance. Cancer Res 69:143-50, 2009 
12. Di Nicolantonio F, Arena S, Tabernero J, et al: Deregulation of the PI3K and KRAS 
signaling pathways in human cancer cells determines their response to everolimus. 
J Clin Invest 120:2858-66, 2010 
13. Tsimberidou AM, Iskander NG, Hong DS, et al: Personalized medicine in a phase I 
clinical trials program: the MD Anderson Cancer Center initiative. Clin Cancer Res 
18:6373-83, 2012 
14. Li J, Yen C, Liaw D, et al: PTEN, a putative protein tyrosine phosphatase gene 
mutated in human brain, breast, and prostate cancer. Science 275:1943-7, 1997 

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Version Date: February 6, 2017 
28 
15. Steck PA, Pershouse MA, Jasser SA, et al: Identification of a candidate tumour 
suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple 
advanced cancers. Nat Genet 15:356-62, 1997 
16. Maehama T, Dixon JE: The tumor suppressor, PTEN/MMAC1, dephosphorylates 
the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem 
273:13375-8, 1998 
17. Shi Y, Paluch BE, Wang X, et al: PTEN at a glance. J Cell Sci 125:4687-92, 2012 
18. Lee JO, Yang H, Georgescu MM, et al: Crystal structure of the PTEN tumor 
suppressor: implications for its phosphoinositide phosphatase activity and 
membrane association. Cell 99:323-34, 1999 
19. Chalhoub N, Baker SJ: PTEN and the PI3-kinase pathway in cancer. Annu Rev 
Pathol 4:127-50, 2009 
20. Song MS, Salmena L, Pandolfi PP: The functions and regulation of the PTEN 
tumour suppressor. Nat Rev Mol Cell Biol 13:283-96, 2012 
21. Garcia JM, Silva J, Pena C, et al: Promoter methylation of the PTEN gene is a 
common molecular change in breast cancer. Genes Chromosomes Cancer 
41:117-24, 2004 
22. Goel A, Arnold CN, Niedzwiecki D, et al: Frequent inactivation of PTEN by 
promoter hypermethylation in microsatellite instability-high sporadic colorectal 
cancers. Cancer Res 64:3014-21, 2004 
23. Janku F, Broaddus R, Bakkar R, et al: PTEN assessment and PI3K/mTOR 
inhibitors: Importance of simultaneous assessment of MAPK pathway aberrations. 
J Clin Oncol 30, 2012 
24. Jia S, Liu Z, Zhang S, et al: Essential roles of PI(3)K-p110beta in cell growth, 
metabolism and tumorigenesis. Nature 454:776-9, 2008 
25. Arkenau HT, Mateo J, Lemech CH, et al: A phase I/II, first-in-human dose-
escalation study of GSK2636771 in patients (pts) with PTEN-deficient advanced 
tumors. J Clin Oncol 32:abstr 2514, 2014 
26. GSK2636771 Investigator's Brochure (March 2014). GlaxoSmithKline (GSK) Group 
Company. 
27. Cheung LW, Yu S, Zhang D, Li J, Ng PK, Panupinthu N, Mitra S, Ju Z, Yu Q, Liang 
H, Hawke DH, Lu Y, Broaddus RR, Mills GB. Naturally occurring neomorphic 
PIK3R1 mutations activate the MAPK pathway, dictating therapeutic response to 
MAPK pathway inhibitors. Cancer Cell. 2014 Oct 13;26(4):479-94. doi: 
10.1016/j.ccell.2014.08.017. Epub 2014 Oct 2. PubMed PMID: 25284480; PubMed 
Central PMCID: PMC4198486. 
28. Ni J, Liu Q, Xie S, Carlson C, Von T, Vogel K, Riddle S, Benes C, Eck M, Roberts 
T, Gray N, Zhao J. Functional characterization of an isoform-selective inhibitor of 
PI3K-p110β as a potential anticancer agent. Cancer Discov. 2012 May; 2 (5): 425-
33. doi: 10.1158/2159-8290.CD-12-0003. Epub 2012 Apr 12. PubMed PMID: 
22588880; PubMed Central PMCID: PMC3384541. 
29. Polivka J Jr, Janku F. Molecular targets for cancer therapy in the PI3K/AKT/mTOR 
pathway. Pharmacol Ther. 2014 May;142(2):164-75. doi: 
10.1016/j.pharmthera.2013.12.004. Epub 2013 Dec 9. Review. PubMed PMID: 
24333502. 

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Molecular Analysis for Therapy Choice (MATCH) 
MATCH Treatment Subprotocol P: GSK2636771 (PTEN Loss) 
Appendix I 
 
Patient Pill Calendar 
Storage: Store at Room Temperature 
Pill Calendar Directions 
1. Take your scheduled dose of each capsule. 
2. If you forget, the missed capsules will not be taken later. 
3. Please bring the empty bottle or any leftover capsules and your pill calendar to your 
next clinic visit. 
4. Take GSK2636771 once daily by mouth either 1 hour before or 2 hours after a meal 
with about 7 ounces of water only. 
5. Swallow capsules whole, do not crush, chew or open capsules. 
 
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Patient Pill Calendar 
This is a calendar on which you are to record the time and number of capsules you take 
each day.  You should take your scheduled dose of each capsule. Note the times and 
the number of capsules 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 capsules and your completed pill calendar to your doctor’s visits. 
GSK2636771 
DAY  
Date 
Time capsule 
taken 
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 
 
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 P: GSK2636771 (PTEN Loss) 
Appendix II 
 
Excluded Mutations for Sub-Protocol EAY131-P 
Exclusion mutations and corresponding Level of Evidence are listed below: 
NOTE: 
A function has been implemented in MATCHBOX to identify any deleterious 
mutations in NF1, NF2, TSC1, TSC2, PIK3R1 genes at Level of Evidence 
code 3. 
Gene 
Name 
Variant ID 
Variant Type 
Level of 
Evidence 
Code 
Variant Description 
NRAS 
COSM585 
SNV 
2 
p.Q61H 
NRAS 
COSM586 
SNV 
2 
p.Q61H 
NRAS 
COSM583 
SNV 
2 
p.Q61L 
NRAS 
COSM584 
SNV 
2 
p.Q61R 
NRAS 
COSM582 
SNV 
2 
p.Q61P 
NRAS 
COSM581 
SNV 
2 
p.Q61E 
NRAS 
COSM580 
SNV 
2 
p.Q61K 
NRAS 
COSM574 
SNV 
2 
p.G13V 
NRAS 
COSM575 
SNV 
2 
p.G13A 
NRAS 
COSM573 
SNV 
2 
p.G13D 
NRAS 
COSM570 
SNV 
2 
p.G13C 
NRAS 
COSM569 
SNV 
2 
p.G13R 
NRAS 
COSM571 
SNV 
2 
p.G13S 
NRAS 
COSM566 
SNV 
2 
p.G12V 
NRAS 
COSM565 
SNV 
2 
p.G12A 
NRAS 
COSM564 
SNV 
2 
p.G12D 
NRAS 
COSM562 
SNV 
2 
p.G12C 
NRAS 
COSM561 
SNV 
2 
p.G12R 
NRAS 
COSM563 
SNV 
2 
p.G12S 
HRAS 
COSM502 
SNV 
2 
p.Q61H 
HRAS 
COSM503 
SNV 
2 
p.Q61H 
HRAS 
COSM498 
SNV 
2 
p.Q61L 
HRAS 
COSM499 
SNV 
2 
p.Q61R 
HRAS 
COSM500 
SNV 
2 
p.Q61P 
HRAS 
COSM497 
SNV 
2 
p.Q61E 
HRAS 
COSM496 
SNV 
2 
p.Q61K 
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Gene 
Name 
Variant ID 
Variant Type 
Level of 
Evidence 
Code 
Variant Description 
HRAS 
COSM489 
SNV 
2 
p.G13V 
HRAS 
COSM490 
SNV 
2 
p.G13D 
HRAS 
COSM488 
SNV 
2 
p.G13C 
HRAS 
COSM486 
SNV 
2 
p.G13R 
HRAS 
COSM487 
SNV 
2 
p.G13S 
HRAS 
COSM483 
SNV 
2 
p.G12V 
HRAS 
COSM485 
SNV 
2 
p.G12A 
HRAS 
COSM484 
SNV 
2 
p.G12D 
HRAS 
COSM481 
SNV 
2 
p.G12C 
HRAS 
COSM482 
SNV 
2 
p.G12R 
HRAS 
COSM480 
SNV 
2 
p.G12S 
KRAS 
COSM555 
SNV 
2 
p.Q61H 
KRAS 
COSM554 
SNV 
2 
p.Q61H 
KRAS 
COSM553 
SNV 
2 
p.Q61L 
KRAS 
COSM552 
SNV 
2 
p.Q61R 
KRAS 
COSM551 
SNV 
2 
p.Q61P 
KRAS 
COSM550 
SNV 
2 
p.Q61E 
KRAS 
COSM549 
SNV 
2 
p.Q61K 
KRAS 
COSM539 
SNV 
2 
p.G15D 
KRAS 
COSM538 
SNV 
2 
p.G15S 
KRAS 
COSM30567 
SNV 
2 
p.G13E 
KRAS 
COSM87280 
SNV 
2 
p.G13E 
KRAS 
COSM534 
SNV 
2 
p.G13V 
KRAS 
COSM533 
SNV 
2 
p.G13A 
KRAS 
COSM532 
SNV 
2 
p.G13D 
KRAS 
COSM527 
SNV 
2 
p.G13C 
KRAS 
COSM529 
SNV 
2 
p.G13R 
KRAS 
COSM528 
SNV 
2 
p.G13S 
KRAS 
COSM512 
SNV 
2 
p.G12F 
KRAS 
COSM514 
SNV 
2 
p.G12L 
KRAS 
COSM13643 
SNV 
2 
p.G12N 
KRAS 
COSM520 
SNV 
2 
p.G12V 
KRAS 
COSM522 
SNV 
2 
p.G12A 
KRAS 
COSM521 
SNV 
2 
p.G12D 

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Version Date: February 6, 2017 
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Gene 
Name 
Variant ID 
Variant Type 
Level of 
Evidence 
Code 
Variant Description 
KRAS 
COSM516 
SNV 
2 
p.G12C 
KRAS 
COSM518 
SNV 
2 
p.G12R 
KRAS 
COSM517 
SNV 
2 
p.G12S 
KRAS 
COSM19404 
SNV 
3 
p. A146T 
BRAF 
COSM1127 
SNV 
2 
p.V600R 
BRAF 
COSM1583011 
SNV 
2 
p.V600R 
BRAF 
COSM308550 
SNV 
2 
p.V600D 
BRAF 
COSM473 
SNV 
1 
p.V600K 
BRAF 
COSM474 
SNV 
2 
p.V600R 
BRAF 
COSM476 
SNV 
1 
p.V600E 
BRAF 
COSM477 
SNV 
2 
p.V600D 
BRAF 
AGTRAP-
BRAF.A5B8.COSF828 
Fusion 
3 
AGTRAP-
BRAF.A5B8.COSF828 
BRAF 
AKAP9-
BRAF.A8B9.COSF101
3 
Fusion 
3 
AKAP9-
BRAF.A8B9.COSF1013 
BRAF 
CDC27-BRAF.C16B9 
Fusion 
3 
CDC27-BRAF.C16B9 
BRAF 
FAM131B-
BRAF.F2B9.COSF118
9 
Fusion 
3 
FAM131B-
BRAF.F2B9.COSF1189 
BRAF 
FCHSD1-
BRAF.F13B9.COSF40
4 
Fusion 
3 
FCHSD1-
BRAF.F13B9.COSF404 
BRAF 
KIAA1549-
BRAF.K16B11 
Fusion 
3 
KIAA1549-BRAF.K16B11 
BRAF 
KIAA1549-
BRAF.K16B9 
Fusion 
3 
KIAA1549-BRAF.K16B9 
BRAF 
KIAA1549-
BRAF.K17B10.COSF5
09 
Fusion 
3 
KIAA1549-
BRAF.K17B10.COSF509 
BRAF 
KIAA1549-
BRAF.K18B10 
Fusion 
3 
KIAA1549-BRAF.K18B10 
BRAF 
KIAA1549-
BRAF.K19B9 
Fusion 
3 
KIAA1549-BRAF.K19B9 
BRAF 
PAPSS1-BRAF.P5B9 
Fusion 
3 
PAPSS1-BRAF.P5B9 
BRAF 
SLC45A3-
BRAF.S1B8.COSF871 
Fusion 
3 
SLC45A3-
BRAF.S1B8.COSF871 
BRAF 
SND1-BRAF.S16B9 
Fusion 
3 
SND1-BRAF.S16B9 

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Version Date: February 6, 2017 
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Gene 
Name 
Variant ID 
Variant Type 
Level of 
Evidence 
Code 
Variant Description 
BRAF 
TAX1BP1-
BRAF.T8B11 
Fusion 
3 
TAX1BP1-BRAF.T8B11 
BRAF 
TRIM24-BRAF.T9B9 
Fusion 
3 
TRIM24-BRAF.T9B9 
BRAF 
COSM1125 
SNV 
3 
L597Q 
BRAF 
COSM1126 
SNV 
3 
L597S 
BRAF 
COSM21612 
SNV 
3 
F595L 
BRAF 
COSM449 
SNV 
3 
G464E 
BRAF 
COSM451 
SNV 
3 
G466V 
BRAF 
COSM450 
SNV 
3 
G464V 
BRAF 
COSM459 
SNV 
3 
G469V 
BRAF 
COSM460 
SNV 
3 
G469A 
BRAF 
COSM461 
SNV 
3 
G469E 
BRAF 
COSM462 
SNV 
3 
N581S 
BRAF 
COSM466 
SNV 
3 
D594V 
BRAF 
COSM467 
SNV 
3 
D594G 
BRAF 
COSM470 
SNV 
3 
L597V 
BRAF 
COSM471 
SNV 
3 
L597R 
BRAF 
COSM472 
SNV 
3 
T599I 
BRAF 
COSM478 
SNV 
3 
K601E 
PIK3CA 
COSM746 
SNV 
2 
p.R88Q 
PIK3CA 
COSM754 
SNV 
2 
p.N345K 
PIK3CA 
COSM757 
SNV 
3 
p.C420R 
PIK3CA 
COSM759 
SNV 
3 
p.P539R 
PIK3CA 
COSM760 
SNV 
3 
p.E542K 
PIK3CA 
COSM763 
SNV 
3 
p.E545K 
PIK3CA 
COSM764 
SNV 
3 
p.E545G 
PIK3CA 
COSM765 
SNV 
2 
p.E545D 
PIK3CA 
COSM767 
SNV 
3 
p.Q546P 
PIK3CA 
COSM775 
SNV 
2 
p.H1047R 
PIK3CA 
COSM776 
SNV 
3 
p.H1047L 
PIK3CA 
COSM12458 
SNV 
3 
p.E545A 
PIK3CA 
COSM766 
SNV 
3 
p.Q546K 
PIK3CA 
COSM12590 
SNV 
3 
p.T1025S 
PIK3CA 
COSM12591 
SNV 
3 
p.M1043V 

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Version Date: February 6, 2017 
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Gene 
Name 
Variant ID 
Variant Type 
Level of 
Evidence 
Code 
Variant Description 
PIK3CA 
COSM29313 
SNV 
3 
p.M1043I 
PIK3CA 
COSM94984 
SNV 
3 
p.M1043I 
PIK3CA 
COSM773 
SNV 
3 
p.M1043I 
PIK3CA 
COSM774 
SNV 
3 
p.H1047Y 
PIK3CA 
COSM27493 
SNV 
3 
p.R93W 
PIK3CA 
COSM748 
SNV 
3 
p.G106V 
PIK3CA 
COSM13570 
SNV 
3 
p.K111E 
PIK3CA 
COSM751 
SNV 
3 
p.G118D 
PIK3CA 
COSM94978 
SNV 
3 
p.N345I 
PIK3CA 
COSM762 
SNV 
3 
p.E542V 
PIK3CA 
COSM6147 
SNV 
3 
p.Q546E 
PIK3CA 
COSM12459 
SNV 
3 
p.Q546R 
PIK3CA 
COSM27504 
SNV 
3 
p.N1044K 
PIK3CA 
COSM12592 
SNV 
3 
p.N1044K 
PIK3CA 
COSM12597 
SNV 
3 
p.G1049R 
PIK3CA 
COSM12584 
SNV 
3 
p.E453K 
PIK3CA 
COSM27133 
SNV 
3 
p.E545Q 
PIK3CA 
COSM27505 
SNV 
3 
p.K111N 
PIK3CA 
COSM12580 
SNV 
3 
p.K111N 
PIK3R1 
COSM85926 
SNV 
3 
p. R348* 
AKT1 
COSM33765 
SNV 
3 
p.E17K 
MTOR 
COSM1686998 
SNV 
3 
p.S2215F 
MTOR 
COSM20417 
SNV 
3 
p.S2215Y 
MTOR 
COSM462604 
SNV 
3 
p.F1888L 
MTOR 
COSM893813 
SNV 
3 
p.F1888L 
MTOR 
OM5 
SNV 
3 
p.F1888L 
MTOR 
OM7 
SNV 
3 
p.F1888I 
MTOR 
COSM180789 
SNV 
3 
p.E1799K 
MTOR 
OM9 
SNV 
3 
p.C1483W 
MTOR 
COSM462616 
SNV 
3 
p.C1483F 
MTOR 
COSM462615 
SNV 
3 
p.C1483Y 
MTOR 
OM12 
SNV 
3 
p.C1483R 
MTOR 
COSM414183 
SNV 
3 
p.L2209V 
MTOR 
COSM462592 
SNV 
3 
p.A2210P 

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Version Date: February 6, 2017 
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Gene 
Name 
Variant ID 
Variant Type 
Level of 
Evidence 
Code 
Variant Description 
MTOR 
COSM462618 
SNV 
3 
p.L1460P 
MTOR 
COSM462619 
SNV 
3 
p.A1459P 
MTOR 
COSM527403 
SNV 
3 
p.N2206S 
MTOR 
COSM1560108 
SNV 
3 
p.S2215P 
MTOR 
COSM3965698 
SNV 
3 
p.L2216P 
MTOR 
MCH4 
SNV 
3 
p.R2217W 

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Version Date: February 6, 2017 
37 
Molecular Analysis for Therapy Choice (MATCH) 
MATCH Treatment Subprotocol P: GSK2636771 (PTEN Loss) 
Appendix III 
 
Patient Drug Information Handout and Wallet Card 
Information for Patients, Their Caregivers and Non-Study Healthcare Team on Possible 
Interactions with Other Drugs and Herbal Supplements 
The patient ____________________________ is enrolled on a clinical trial using the 
experimental study drug, GSK2636771.  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: 
GSK2636771 has the following qualities: 
• 
Is highly protein-bound and may prevent other drugs from binding to blood protein. Patients 
receiving other medications that are also highly protein bound may need to be monitored more 
frequently. 
• 
Is primarily broken down by UGT enzymes and may be affected by other drugs that strongly 
inhibit or induce these enzymes.   
• 
May enhance the antiplatelet activity of agents that are irreversible (aspirin) or that act through 
platelet purinergic receptors like clopidogrel, ticlopidine and prasugrel 
To the patient: Take this paper with you to your medical appointments and keep the 
attached information card in your wallet.   
GSK2636771 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:  
GSK2636771 must be used very carefully with other medicines that are highly protein-bound or 
avoided with other medicines that affect platelets to thin your blood, including aspirin. 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 highly protein-bound or affect 
platelet activity. 
• 
Please be very careful!  Over-the-counter drugs (including herbal supplements) 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.  
• 
Patients receiving other medications that are also highly protein bound may need to be 
monitored more frequently. 
• 
Your regular health care provider should check a frequently updated medical reference or call 
Rev. 12/16 
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Version Date: February 6, 2017 
38 
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 GSK2636771.  This clinical trial is sponsored by the NCI.  
GSK2636771 may interact with drugs that are strong inhibitors or 
inducers of UGT, highly protein-bound or affect platelet activity, 
like aspirin.  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. 
➢ GSK2636771 may interact with drugs that affect UGT liver 
enzymes, is highly-protein bound and may interact with other drugs 
that are bound to blood protein or drugs that affect platelets 
to thin blood. It must be used very carefully with other medicines 
that are also highly-protein bound or avoided with other 
medicines that affect platelet activity.  
➢ 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 
inhibitors or inducers of UGT, highly protein-bound or affect 
platelet activity, like aspirin, clopidogrel, ticlopidine, and 
prasugrel. 
➢ 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 _________________________________.