MATCH Treatment Subprotocol I: GDC-0032 (Taselisib) in Patients With Tumors (Other Than Breast Cancer) With PIK3CA Mutation But Without KRAS Mutation or PTEN Loss
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 
 
 
January 25, 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 #18 to EAY131-I, Molecular Analysis for Therapy Choice (MATCH): 
MATCH Treatment Subprotocol I: GDC-0032 (taselisib) in Patients with Tumors (other than 
breast cancer) with PIK3CA Mutation but without KRAS Mutation or PTEN Loss.  
This addendum is in response to Dr. L. Austin Doyle’s January 22, 2019 Request for Rapid 
Amendment for GDC-0032. 
The following revisions to the EAY131-I protocol have been made in this addendum: 
 
Section 
Change 
1. 
Cover Page 
Updated Version Date.  
2. 
Section 3.3 
Updated the GDC-0032 CAEPR list with version 2.2, October 11, 2018. 
The following revisions to EAY131-I 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 GDC-0032 risk list with version 2.2, October 11, 2018. 
If you have any questions regarding this addendum, please contact kpollard@ecog-acrin.org or 
857-504-2900. 
We request review and approval of this addendum to EAY131-I so ECOG-ACRIN may activate 
it promptly. 
Thank you.  
Sincerely, 
Pamela Cogliano 
Senior Director of Protocol Development 

 
ii 
Enclosure 
CC: Ian Krop, M.D., Ph.D. 
Juneko Grilley-Olson, M.D.  
Josh Lauring, M.D., Ph.D. 
Alice Chen, MD 
Keith Thomas Flaherty, 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, PhD 
Susanna Lee, MD, PhD 
Constantine Gastonis, PhD 
Paolo Caimi, MD 
Shaji Kumar, MD 
Carlos Arteaga, MD 
Edith Mitchell, MD 
John J. Wright, MD, PhD 
Lyndsay Harris, MD 
James Tricoli, PhD 
 
 
Bruce Giantonio, MD 
Donna Marinucci 
Kerry Higgins 
Gayle Ipock 
Jean MacDonald 
Carol Chami, R.N. 
Julianne Human 
Kelly Redmond 
Jennifer VanCamp 
Daniel Reeve 
Angela Chen 
Becky Fillingham 
Jeffrey Zhang 
Kevin Pollard 
Amy Li 
Abuchi Agu 
Michael T. Balco 
Lauren Lambert 
Cayden Maican 
Margaret Cavenagh 
Ben Kim 
Russell McDaniel 
Alexandra Sachs 
 
 

EAY131-I 
1 
Molecular Analysis for Therapy Choice (MATCH) 
MATCH Treatment Subprotocol I: GDC-0032 (taselisib) in 
Patients with Tumors (other than breast cancer) with 
PIK3CA Mutation but without KRAS Mutation or PTEN Loss 
GDC-0032 (TASELISIB) TREATMENT 
SUBPROTOCOL CHAIR: 
Ian Krop, M.D., Ph.D. 
GDC-0032 (TASELISIB) TREATMENT 
SUBPROTOCOL CO-CHAIR: 
Juneko Grilley-Olson, M.D. 
GDC-0032 (TASELISIB) TRANSLATIONAL 
CHAIR: 
Josh Lauring, M.D., Ph.D. 
Version Date:  January 25, 2019 
NOTE: This subprotocol (EAY131-I) 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 
February 25, 2016 (Incorporated in Addendum #2) 
Addendum #3 – 5/16 
Addendum #4 – 7/16 
Addendum #5 – 12/16 
Addendum #7 – 3/17 
Addendum #13 
Addendum #18 
Agent 
IND# 
NSC# 
Supply 
GDC-0032 (taselisib) 
NCI Supplied 
Rev. Add13 

ECOG-ACRIN 
EAY131-I 
Cancer Research Group 
Version Date: January 25, 2019 
2 
Table of Contents 
Molecular Analysis for Therapy Choice (MATCH) ...................................................... i 
MATCH Treatment Subprotocol I: GDC-0032 (taselisib) in Patients with Tumors 
(other than breast cancer) with PIK3CA Mutation but without KRAS Mutation 
or PTEN Loss ........................................................................................................ 1 
Table of Contents ...................................................................................................... 2 
Schema ...................................................................................................................... 4 
1. Introduction ........................................................................................................ 5 
1.1 GDC-0032 (taselisib) .................................................................................. 5 
1.2 Supporting Preliminary Data ..................................................................... 5 
2. Selection of Patients ......................................................................................... 10 
2.1 Eligibility Criteria ..................................................................................... 10 
3. GDC-0032 (taselisib) Treatment Plan................................................................ 12 
3.1 Dosage and Administration ..................................................................... 12 
3.2 Adverse Event Reporting Requirements ................................................. 12 
3.3 Comprehensive Adverse Events and Potential Risks List (CAEPR) for 
GDC-0032 (Taselisib, NSC 778795) .......................................................... 15 
3.4 Dose Modifications ................................................................................. 17 
3.5 Supportive Care ....................................................................................... 24 
3.6 Duration of Agent-specific treatment ..................................................... 24 
3.7 Duration of Follow-Up ............................................................................. 24 
4. Study Parameters .............................................................................................. 25 
4.1 Therapeutic Parameters for GDC-0032 (taselisib) Treatment ................ 25 
5. Drug Formulation and Procurement ................................................................. 27 
5.1 GDC-0032 (NSC #778795) ....................................................................... 28 
6. Translational Studies ......................................................................................... 30 
7. References ........................................................................................................ 30 
Appendix I  Patient Pill Calendar ............................................................................. 32 
Appendix II  Actionable Mutations for Sub-Protocol EAY131-I ............................... 34 
Appendix III  Patient Drug Information Handout and Wallet Card ......................... 38 
 

ECOG-ACRIN 
EAY131-I 
Cancer Research Group 
Version Date: January 25, 2019 
3 
 
TREATMENT SUBPROTOCOL CHAIR 
Ian Krop, M.D. Ph.D. 
Dana Farber Cancer Institute 
450 Brookline Avenue YC1235 
Boston, MA 02215 
Phone: (617) 632-1930 
Fax: (617) 632-5958 
E-mail: ikrop@partners.org 
 
TREATMENT SUBPROTOCOL CO-CHAIR  
Juneko E. Grilley-Olson, M.D. 
University of North Carolina 
Division of Hematology/Oncology  
170 Manning Drive  
Physicians Office Third Floor CB#7305  
Chapel Hill, NC 27599 
Phone: (919) 843-5497 
Fax: (919) 966-6735 
E-mail: juneko_grilley@med.unc.edu 
 
TRANSLATIONAL CHAIR 
Josh Lauring, M.D. Ph.D. 
Johns Hopkins University 
1650 Orleans Street 
CRB 1 Room 146 
Baltimore, MD 21287 
Phone: (410) 502-8164 
Fax: (410) 614-4073 
E-mail: jlauring@jhmi.edu 
 
 
 
 
 
 
 
 
 
 
 

ECOG-ACRIN 
EAY131-I 
Cancer Research Group 
Version Date: January 25, 2019 
4 
Schema 
 
Long-Term Follow-Up
GDC-0032 (taselisib) 4mg po daily
Cycle = 28 days
Accrual Goal: 70
 
 
Rev. 3/17 

ECOG-ACRIN 
EAY131-I 
Cancer Research Group 
Version Date: January 25, 2019 
5 
1. 
Introduction 
1.1 
GDC-0032 (taselisib) 
GDC-0032 (taselisib) is a potent, selective inhibitor of Class I phosphoinositide 3-
kinase (PI3K) alpha, delta, and gamma isoforms, with approximately 30-fold less 
inhibition of the p110 beta isoform. 
1.2 
Supporting Preliminary Data  
Rationale:  
PI3K is a lipid kinase involved in tumor cell proliferation, survival, and migration 
upon activation by growth factor receptors and integrins. PI3K catalyzes the 
phosphorylation of phosphatidylinositol-4,5-bisphosphate (PIP2) to generate 
phosphatidylinositol-3,4,5-trisphosphate (PIP3), a second messenger involved in 
the phosphorylation of Akt and associated proteins in the Akt/mammalian target 
of rapamycin (mTOR) pathway1,2. Activating and transforming mutations of the 
gene encoding the p110 alpha subunit of PI3K (PIK3CA) are commonly found in 
solid and hematological tumors1,3-5. For example, PIK3CA mutations were found 
in 17-18% of 6234 tumors listed on cBioPortal (http://www.cbioportal.org/public-
portal/). In addition, the PI3K/Akt pathway is activated in numerous types of 
cancer by receptor tyrosine kinase (RTK) signaling, loss of the phosphatase and 
tensin homolog (PTEN), or rat sarcoma (RAS) mutations. In nonclinical studies, 
pan-class I PI3K inhibitors and alpha isoform selective PI3K inhibitors show 
greater potency against cell lines with PIK3CA mutations. Janku et al analyzed 
characteristics and outcome of over 1600 patients with diverse advanced tumors 
and PIK3CA mutations.  Of 160 patients found to have PIK3CA mutations, the 
majority of the mutations occurred in three hotspots: E545K (1633G > A) in 
32.5%; E542K (1624G > A) in 20% and H1047R (3140A > G) in 18%. These 
hotspot mutations in PIK3CA, in addition to a number of less frequent mutations 
(Appendix II), have been shown to increase the lipid kinase activity of PIK3CA 
and increase phosphorylation of downstream signaling targets6-10. There was an 
improved response rate in patients with PIK3CA mutations or PTEN loss who 
were treated with allosteric mTOR inhibitors, AKT inhibitors or PI3K inhibitors 
compared to similar patients treated with similar agents, but not having PIK3CA 
mutations or PTEN loss, and compared to patients with PIK3CA mutations or 
PTEN loss treated with agents that do not target the PI3K-AKT-mTOR pathway11. 
The PTEN protein is a tumor suppressor protein that negatively regulates the 
PI3K pathway thorough its lipid phosphatase activity, dephosphorylating PIP3 to 
PIP2. PTEN function can be reduced or abrogated in tumors by loss of 
expression resulting from either genetic or epigenetic causes. Protein loss can be 
detected by absence of staining using immunohistochemistry. Genetic causes of 
PTEN inactivation include heterozygous and homozygous gene deletion, 
frameshift, indel, and nonsense mutations causing protein truncation or 
nonsense mediated mRNA decay, as well as missense mutations that alter 
amino acids critical for PTEN’s enzymatic activity (Appendix II)12,13. Several 
preclinical studies have shown that PTEN-deficient tumors preferentially depend 
on the beta isoform of PI3K for survival and respond to beta-specific, but not 
alpha-specific, inhibitors14-16. A clinical case report showed that PTEN mutations 
can be an acquired resistance mechanism to an alpha-specific PI3K inhibitor17. 
Additional studies have shown that RAS mutations, KRAS mutations in particular, 

ECOG-ACRIN 
EAY131-I 
Cancer Research Group 
Version Date: January 25, 2019 
6 
are associated with resistance to PI3K inhibitors, even in the context of a cell line 
with a PIK3CA mutation18,19. This effect of activating RAS mutations appears to 
be due to the activation of the mitogen activated protein kinase (MAPK) pathway, 
leading to preservation of phosphorylation of critical downstream substrates such 
as ribosomal protein S6 and EIF4EBP1, even in the face of PI3K inhibition19. The 
beta isoform of PI3K is involved in glucose metabolism as evidenced by 
increased glucose levels in conditional p110 knockout mice compared with wild-
type mice following a glucose challenge test15. These data provide a strong 
rationale for developing beta isoform-sparing PI3K inhibitors that inhibit the PI3K 
pathway in human tumors while minimizing effects on glucose metabolism. In 
summary, use of a beta-isoform sparing PI3K inhibitor is predicted to have 
enhanced efficacy and tolerability against tumors harboring activating PIK3CA 
mutations, but without activating KRAS mutations or PTEN loss or loss-of-
function mutations. 
Nonclinical studies: 
GDC-0032 (taselisib) is a potent inhibitor of Class I PI3K alpha, delta, and 
gamma isoforms (mean apparent Ki [Kiapp] values of 0.29 nM, 0.12 nM, and 0.97 
nM, respectively), and approximately 30-fold less potent against the beta isoform 
(Ki 9.1 nM) compared to the alpha isoform. GDC-0032 (taselisib) has 
demonstrated activity in nonclinical models of PI3K-mutant tumor cells in vitro 
and in vivo. Studies of the mechanism of action indicate that downstream PI3K 
pathway components such as Akt, PRAS40, and S6 are inhibited, resulting in G1 
arrest and apoptosis. GDC-0032 (taselisib) has been proven to be potent in 
nonclinical xenograft models of PI3K-mutant breast tumors following PO daily 
(QD), as well as intermittent, dosing. Single-agent GDC-0032 (taselisib) resulted 
in 128% tumor growth inhibition (TGI) at a maximum tolerated dose (MTD) of 25 
mg/kg QD (7 partial regressions [PRs] and 1 complete regression [CR] out of 8 
animals) in the KPL-4 breast cancer xenograft model, which contains a PIK3CA 
mutation in the catalytic domain of p110 alpha (H1047R), in severe combined 
immunodeficient (SCID) beige mice; 105% TGI at an MTD of 22.5 mg/kg QD (6 
PRs out of 8 animals) in the MCF7-neo/HER2 breast cancer xenograft model, 
which contains a PIK3CA mutation in the helical domain of p110 alpha (E545K), 
in nude mice; and 94% TGI at a dose of 20 mg/kg QD in the A549 NSCLC 
xenograft model, which contains a K-ras mutation, in nude mice. GDC-0032 
(taselisib) is potent against a panel of human cell lines but significantly more 
potent against cell lines that contain PI3K mutations: mean IC50s for the PI3K 
wild-type and PI3K mutant were 2.6 and 0.06 μM, respectively. 
Clinical studies: 
Study PMT4979g is an open-label, first-in-human, Phase I/II dose-escalation 
study designed to define the safety, tolerability, and PK and pharmacodynamic 
(PD) effects in patients with locally advanced or metastatic solid tumors. A dose-
escalation stage evaluated the safety and pharmacokinetics of increasing doses 
of GDC-0032 (taselisib) administered once daily (QD) in a 28-day cycle. The 
single-agent expansion cohorts enrolled patients with PIK3CA-mutant breast 
cancer, PIK3CA-mutant solid tumors other than breast cancer, solid tumors, 
human epidermal growth factor receptor 2 (HER2)-positive breast cancers, 
PIK3CA-amplified solid tumors, and PIK3CA-mutant non-breast, non-colorectal 
solid tumors. Additional cohorts have enrolled patients with hormone receptor-
positive breast cancer to receive GDC-0032 (taselisib) in combination with either 

ECOG-ACRIN 
EAY131-I 
Cancer Research Group 
Version Date: January 25, 2019 
7 
letrozole or fulvestrant. In the Phase II portion of the study, 60 postmenopausal 
patients with locally advanced or metastatic HER2-negative, hormone receptor–
positive breast cancer have received combination treatment with fulvestrant and 
GDC-0032 (taselisib). 
Study GO27802 is an open-label, multicenter, Phase Ib dose-escalation study 
designed to assess the safety, tolerability, and pharmacokinetics of oral GDC-
0032 (taselisib) administered in combination with either docetaxel or paclitaxel in 
patients with HER2-negative locally recurrent or metastatic breast cancer or non-
small-cell lung cancer (NSCLC). In studies PMT4979g and GO27802, as of 30 
July 2014, a total of 246 patients have been treated with GDC-0032 (taselisib) 
either as a single agent (n = 115) or in combination with fulvestrant (n = 87), 
letrozole (n = 28), docetaxel (n = 4), or paclitaxel (n = 12). 
Preliminary Pharmacokinetics 
PK data are available from 30 patients treated with GDC-0032 (taselisib) at 3, 5, 
8, 12, and 16 mg capsules in the ongoing Phase I clinical trial (Study 
PMT4979g). The cohort mean apparent clearance (CL/F) and the terminal 
half-life (t1/2) following a single oral dose of GDC-0032 (taselisib) had a range of 
4.779.17 L/hour and 37.243.8 hours, respectively. Following daily oral dosing 
for 8 days, there was a 2- to 4-fold accumulation of GDC-0032 (taselisib). The 
pharmacokinetics of GDC-0032 (taselisib) appear to be dose linear and time 
independent. Results from the mass balance study suggest that hepatic 
elimination of unchanged GDC-0032 (taselisib) represents the predominant 
pathway of elimination, with renal elimination a minor route of total clearance. No 
GDC-0032 (taselisib)-related metabolites were identified in systemic circulation. 
GDC-0032 (taselisib) was metabolized primarily by CYP3A4 in human liver 
microsomes and appeared to be a weak time-dependent inhibitor of CYP3A4.  
Although in vitro induction studies in human hepatocytes suggested that GDC-
0032 (taselisib) has low to moderate potential to induce CYP3A4, preliminary 
data from the Phase I study (PMT4979g) indicate that 9 mg capsule dose of 
GDC-0032 (taselisib) daily for 2 weeks in patients had no apparent effect on the 
pharmacokinetics of midazolam (a sensitive CYP3A4 substrate). Therefore, 
GDC-0032 (taselisib) may be administered concomitantly with CYP3A4 
substrates without the risk of a pharmacokinetic drug-drug interaction. Co-
administration of taselisib with a strong CYP3A4 inhibitor, itraconazole, or a 
potent CYP3A4 inducer, rifampin, resulted in an approximate 49% increase and 
23% decrease, respectively, in taselisib exposure (AUC). There was no apparent 
food effect on pharmacokinetics. 
Preliminary Pharmacodynamics 
Tumor biopsies were obtained from 2 NSCLC patients during screening (baseline 
biopsy) and once during Cycle 1 in Study PMT4979g (on-treatment biopsy). The 
on-treatment biopsy was obtained 1 to 4 hours after dosing at approximately Day 
18 (between Days 15 and 21). Needle core biopsies were fixed in optimal cutting 
temperature compound and evaluated by reverse phase protein array for Akt 
pathway markers, including phospho-Akt. Decreases of > 60% in pAkt and pS6 
(compared with baseline) were demonstrated in these patients who were treated 
with GDC-0032 (taselisib) at capsule doses of 3 mg and 16 mg QD. 

ECOG-ACRIN 
EAY131-I 
Cancer Research Group 
Version Date: January 25, 2019 
8 
Concentration QT/QTc Analysis 
Preliminary C-QT analysis was conducted using 911 data points from 146 
patients for QTcF and using 759 data points from 132 patients for QTcF CFB. 
The C-QT analysis showed a weak positive correlation between GDC-0032 
(taselisib) plasma concentration and QTcF and QTcF CFB within the available 
exposure range of GDC-0032 (taselisib). Within the 6-mg exposure range, the 
upper level of the CI around the median profile of QTcF CFB reaches 
approximately 10 ms and excludes 20 ms (criteria suggested by FDA for 
oncology drugs). 
Safety: 
Ninety-six of the 115 patients (83%) treated with single-agent GDC-0032 
(taselisib) experienced at least 1 adverse event that was assessed by the 
investigator as related to GDC-0032 (taselisib). 
Adverse events that occurred in ≥ 10% of patients that were assessed by the 
investigator as related to GDC-0032 (taselisib) were diarrhea (52%), 
hyperglycemia (35%), nausea (35%), fatigue (31%), decreased appetite (25%), 
rash (18%), stomatitis (15%), vomiting (13%), and mucosal inflammation (12%). 
Among the 115 patients treated with single-agent GDC-0032 (taselisib), at least 
one Grade 3 or higher adverse event was reported for 72 patients (63%). Events 
reported for more than 1 patient included hyperglycemia (14%), colitis (6%), 
diarrhea (5%), hypokalemia (5%), pneumonitis (5%), anemia (4%), fatigue (4%), 
rash (4%), abdominal pain (3%), increased ALT (3%), dyspnea (3%), 
hyponatremia (3%), hypophosphatemia (3%), increased lipase (3%), pneumonia 
(3%), UTI (3%), congestive cardiac failure (2%), Clostridium difficile infection 
(2%), hypoxia (2%), neutropenia (2%), pruritus (2%), respiratory failure (2%), and 
stomatitis (2%). 
Efficacy: 
Preliminary efficacy data as of 30 July 2014 for patients enrolled in the Phase I/II 
study PMT4979g with measurable disease at baseline and known PIK3CA 
mutation status show that treatment with GDC-0032 (taselisib) alone or in 
combination with fulvestrant or letrozole appears to result in more pronounced 
anti-tumor activity in patients with PIK3CA-mutant tumors compared to those 
without the mutation, including in patients with breast cancer. In the single-agent 
GDC-0032 (taselisib) group, 11 of 91 patients (12%) with measurable disease at 
baseline had a partial response as their best overall response, with 9 having 
confirmed partial responses per Response Evaluation Criteria In Solid Tumors 
(RECIST) 1.1. All 11 partial responses were observed in the 53 patients with 
PIK3CA-mutant positive tumors (21%), whereas none were seen in the 38 
patients without detectable PIK3CA mutation. Thirty-four patients treated with 
single-agent GDC-0032 (taselisib) had been diagnosed with breast cancer, and 
among those, partial responses were observed in 7 patients (21%), all of whom 
had tumors harboring PIK3CA mutations. Six patients had confirmed partial 
responses per RECIST 1.1. The PR rate in breast cancer patients with PIK3CA 
mutations treated with single agent GDC-0032 (taselisib) was 7 out of 25 (28%). 
Stable disease as best overall response was observed in 34% of patients with 
PIK3CA mutant tumors and 39% of those with PIK3CA wild type tumors, for an 
overall SD rate of 36% across all tumor types. 

ECOG-ACRIN 
EAY131-I 
Cancer Research Group 
Version Date: January 25, 2019 
9 
In the 63 patients with measurable disease at baseline receiving GDC-0032 
(taselisib) in combination with fulvestrant, 1 (2%) had a complete response and 
19 (30%) had a partial response as their best overall response, with 14 having 
confirmed partial responses per RECIST 1.1. Twelve of the partial responses 
were observed in the 33 patients (36%) with PIK3CA-mutant positive tumors, 
whereas the remaining 7 were seen in the 30 patients (23%) without detectable 
PIK3CA mutation. The single complete response was observed in a patient 
without detectable PIK3CA mutation but was not confirmed. In the 20 patients 
with measurable disease at baseline receiving GDC-0032 (taselisib) in 
combination with letrozole, 5 (25%) had a partial response as their best overall 
response, with 4 being confirmed partial responses per RECIST 1.1. Four of the 
partial responses were observed in the 10 patients (40%) with PIK3CA-mutant 
positive tumors, whereas 1 was seen in the 10 patients (10%) without detectable 
PIK3CA mutation. In this early trial, nine (12%) of the 73 patients had a partial 
response as best response, of which 6 patients had a confirmed partial response. 
Twenty-eight patients (38%) had a best confirmed response of stable disease per 
RECIST. 
Because GDC-0032 (taselisib) has demonstrated an objective response rate in 
patients with PIK3CA mutant breast cancer in excess of the primary endpoint of 
MATCH, patients with breast cancer will be excluded from this study. The effect 
of GDC-0032 (taselisib) on patients with PIK3CA mutant, but not amplified, 
squamous cell carcinoma of the lung is being evaluated in a separate basket 
study and therefore this PIK3CA patient population will also be excluded from the 
current study. 
In summary, GDC-0032 (taselisib) is a potent inhibitor of class I PI3K isoforms 
alpha, gamma, and delta with less potency against the beta isoform, which has 
demonstrated an acceptable safety profile in clinical studies to date and has 
shown preliminary evidence of single agent efficacy against tumors of various 
types, with higher observed response rates against tumors with PIK3CA 
mutations. The recommended phase II dose is 9 mg (capsule form), equivalent to 
4-6 mg (tablet form). The tablet formulation has been selected for further clinical 
development. For this study, the 4mg (tablet) once daily dosing will be used, 
since clinical activity has been observed at this dose level and this dose will 
maximize tolerability. Please refer to the GDC-0032 (taselisib) Investigator’s 
Brochure for additional details. 

ECOG-ACRIN 
EAY131-I 
Cancer Research Group 
Version Date: January 25, 2019 
10 
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 a PIK3CA mutation as determined via the MATCH 
Master Protocol. See Appendix II for a list of the eligible PIK3CA 
alterations and corresponding Levels of Evidence. 
2.1.3 
Patients must have an electrocardiogram (ECG) within 8 weeks prior 
to treatment assignment and must have no clinically important 
abnormalities in rhythm, conduction or morphology of resting ECG 
(e.g. complete left bundle branch block, third degree heart block). 
Date of ECG:  _______________ 
2.1.4 
Patients with known left ventricular dysfunction must have ECHO or 
MUGA within 4 weeks prior to registration to treatment and must not 
have left ventricular ejection fraction (LVEF) < institutional lower limit 
of normal (LLN). If the LLN is not defined at a site, the LVEF must be 
> 50% for the patient to be eligible. 
Date of ECHO/MUGA:  _______________ 
Rev. Add13 

ECOG-ACRIN 
EAY131-I 
Cancer Research Group 
Version Date: January 25, 2019 
11 
2.1.5 
Patients must not have known hypersensitivity to GDC-0032 
(taselisib) or compounds of similar chemical or biologic composition. 
2.1.6 
Patients must have a fasting glucose ≤ 125 mg/dL 
NOTE: 
Please provide clear documentation that the glucose test 
was conducted at a fasting state. 
2.1.7 
Patients must not have breast cancer. 
2.1.8 
Patients with squamous cell carcinoma of the lung who have PIK3CA 
mutations who have access to AND are eligible for Lung-MAP 
(S1400) are not eligible. 
2.1.9 
Patients must not have KRAS mutations, and/or PTEN mutation or 
loss, detected in the tumor sample as determined by the MATCH 
screening assessment. PTEN loss will be determined by 
immunohistochemistry. See Appendix II for a list of the exclusionary 
KRAS and PTEN alterations and corresponding Levels of Evidence. 
2.1.10 
Patients must not have had prior therapy with a PI3K inhibitor or 
PI3K/mTOR inhibitor. These include, but are not limited to: BEZ235, 
XL-765 (SAR245409), GDC-0980, PF-04691502, PF-05212384 (PKI-
587), SF-1126, GSK 2126458, P-7170, BGT-226, LY3023414, GDC-
0084, DS-7423, BKM-120 (buparlisib), PX-866, XL-147, GDC-0941 
(pictilisib), VS-5584, BAY-80-6946, ZSTK-474, WX 037, AZD8835, 
GSK2636771, GS-9820, BYL719, MLN1117 (INK1117), Idelalisib, 
TGR1202, RP6530, duvelisib (IPI-145), CUDC-907. Prior GDC-0032 
(taselisib) is not allowed. 
2.1.11 
Patients must not have had prior therapy with an Akt inhibitor. These 
include, but are not limited to: MK-2206, GSK690693, AZD5363, 
triciribine, perifosine, GSK2141795, GSK2110183, SR13668, 
BAY1125976, GDC-0068 (ipatasertib), LY2780301, ARQ092. 
2.1.12 
Patients with prior treatment with an mTOR inhibitor are acceptable. 
These include, but are not limited to: temsirolimus, everolimus, 
ridaforolimus, sirolimus, CC-223, MLN128 (INK128), DS-3078, CC-
115, AZD-2014, AZD8055. 
2.1.13 
Patients must not have type 1 or 2 diabetes requiring 
anti-hyperglycemic medication (e.g. metformin, glipizide, insulin) 
2.1.14 
Patients must not have current dyspnea at rest or require any daily 
supplemental oxygen 
2.1.15 
Patients must not have history of inflammatory bowel disease (e.g. 
Crohn’s disease or ulcerative colitis) or active bowel inflammation 
(e.g. diverticulitis) 
 
 
 
 
 
Physician Signature 
 
Date 
OPTIONAL: 
This signature line is provided for use by institutions wishing to 
use the eligibility checklist as source documentation. 
Rev. 12/16 

ECOG-ACRIN 
EAY131-I 
Cancer Research Group 
Version Date: January 25, 2019 
12 
3. 
GDC-0032 (taselisib) Treatment Plan 
3.1 
Dosage and Administration 
The dose of GDC-0032 (taselisib) on this study will be 4 mg taken orally once a 
day (4 mg PO QD) on a 28 day cycle. GDC-0032 (taselisib) is formulated as 2 
mg tablets, so patients will take two 2 mg tablets once daily to receive a 4 mg 
dose. Patients will repeat cycles until progression. 
Patients should take the GDC-0032 (taselisib) dose at the same approximate 
time each day without regard to the timing of administration of food. If a dose is 
missed (not taken within 6 hours after the scheduled dosing time), the patient 
should resume dosing with the next scheduled dose. Missed or vomited doses 
will not be made up. 
Guidelines for dosage modification and treatment interruption or discontinuation 
are provided in Sections 3.4 and 3.6. 
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 I 
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 I 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 GDC-0032 
(taselisib), or within 28 days of the subject’s last dose of GDC-
0032 (taselisib), 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. 
 

ECOG-ACRIN 
EAY131-I 
Cancer Research Group 
Version Date: January 25, 2019 
13 
EAY131 – Subprotocol I specific expedited reporting 
exceptions: 
For Subprotocol I, 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  
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 

ECOG-ACRIN 
EAY131-I 
Cancer Research Group 
Version Date: January 25, 2019 
14 
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. 

ECOG-ACRIN 
EAY131-I 
Cancer Research Group 
Version Date: January 25, 2019 
15 
3.3 
Comprehensive Adverse Events and Potential Risks List (CAEPR) for GDC-0032 
(Taselisib, NSC 778795) 
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 910 patients. 
Below is the CAEPR for GDC-0032 (taselisib). 
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 2.2, October 11, 20181 
 
Adverse Events with Possible 
Relationship to GDC-0032 (taselisib) 
(CTCAE 5.0 Term) 
[n= 910] 
 
 
Specific Protocol 
Exceptions to 
Expedited Reporting 
(SPEER) 
 
Likely (>20%) 
Less Likely (<=20%) 
Rare but Serious (<3%)   
GASTROINTESTINAL DISORDERS 
  
 
Abdominal pain 
 
  
 
Colitis 
 
 Colitis (Gr 2) 
Diarrhea 
 
 
 Diarrhea (Gr 3) 
 
Dyspepsia 
 
  
 
Mucositis oral 
 
 Mucositis oral (Gr 3) 
Nausea 
 
 
 Nausea (Gr 2) 
 
Vomiting 
 
 Vomiting (Gr 2) 
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS 
  
Fatigue 
 
 
 Fatigue (Gr 2) 
 
 Fever 
 
  
INFECTIONS AND INFESTATIONS 
  
 
Infection2 
 
  
INVESTIGATIONS 
  
 
Weight loss 
 
  
METABOLISM AND NUTRITION DISORDERS 
  
 
Anorexia 
 
 Anorexia (Gr 2) 
Hyperglycemia 
 
 
 Hyperglycemia (Gr 3) 
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS 
  
 
Pneumonitis 
 
  
Rev. 7/16 
Rev. Add18 

ECOG-ACRIN 
EAY131-I 
Cancer Research Group 
Version Date: January 25, 2019 
16 
 
Adverse Events with Possible 
Relationship to GDC-0032 (taselisib) 
(CTCAE 5.0 Term) 
[n= 910] 
 
 
Specific Protocol 
Exceptions to 
Expedited Reporting 
(SPEER) 
 
Likely (>20%) 
Less Likely (<=20%) 
Rare but Serious (<3%)   
SKIN AND SUBCUTANEOUS TISSUE DISORDERS 
  
 
Alopecia 
 
  
 
Dry skin 
 
  
 
Skin and subcutaneous 
tissue disorders - Other 
(rash)3 
 
 
Skin and 
subcutaneous tissue 
disorders - Other 
(rash)3 (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 Infections, including serious infections, includes all 75 sites of infection under the INFECTIONS AND 
INFESTATIONS SOC. 
3 Rash may include rash, rash erythematous, rash follicular, rash generalized, rash macular, rash maculo-
papular, rash maculovesicular, rash morbilliform, rash papular, rash papulosquamous, rash pruritic, rash 
pustular, and rash vesicular. 
Adverse events reported on GDC-0032 (taselisib) trials, but for which there is insufficient 
evidence to suggest that there was a reasonable possibility GDC-0032 (taselisib) caused 
the adverse event:  
BLOOD AND LYMPHATIC SYSTEM DISORDERS - Anemia 
EAR AND LABYRINTH DISORDERS - Vertigo 
GASTROINTESTINAL DISORDERS - Constipation; Dry mouth; Dysphagia; Enterocolitis; 
Gastrointestinal disorders - Other (Crohn's disease); Oral pain; Rectal fistula 
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS – Death NOS 
INVESTIGATIONS - Alanine aminotransferase increased; Aspartate aminotransferase 
increased; Cholesterol high; Lymphocyte count decreased; Neutrophil count decreased; White 
blood cell decreased 
METABOLISM AND NUTRITION DISORDERS - Dehydration; Hypokalemia 
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS - Muscle cramp; Myalgia 
NERVOUS SYSTEM DISORDERS - Dizziness; Dysgeusia; Headache; Nervous system 
disorders - Other (neuropathy peripheral); Stroke 
PSYCHIATRIC DISORDERS - Psychiatric disorders - Other (mood altered) 
RENAL AND URINARY DISORDERS - Acute kidney injury 
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS - Cough; Respiratory failure 
SKIN AND SUBCUTANEOUS TISSUE DISORDERS - Erythema multiforme; Erythroderma; 
Pruritus 
NOTE: 
GDC-0032 (Taselisib) 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. 
 

ECOG-ACRIN 
EAY131-I 
Cancer Research Group 
Version Date: January 25, 2019 
17 
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). 
The side effects observed with GDC-0032 (taselisib) are consistent with those 
observed with other PI3K inhibitors.  Selected toxicities of interest for GDC-0032 
(taselisib) include gastrointestinal toxicities, pneumonitis, rash, stomatitis, and 
hyperglycemia and these are described in detail below. Certain adverse events 
(e.g., rash, colitis, and pneumonitis) may also occur within 4 weeks of holding or 
stopping GDC-0032 (taselisib). 
The GDC-0032 (taselisib) dose reduction instructions provided in Table 1 are 
intended to serve as recommended guidelines to allow ongoing treatment for 
patients experiencing clinical benefit without signs or symptoms of progression 
while monitoring patient safety.  The investigator may temporarily suspend GDC-
0032 (taselisib) dosing for up to 28 days from the last scheduled dose due to a 
GDC-0032 (taselisib)-related toxicity or an unanticipated medical event not 
associated with study treatment toxicity or with disease progression. Depending 
on the nature and the severity of the GDC-0032 (taselisib)-related toxicity, the 
investigator may resume GDC-0032 (taselisib) dosing in the patient at the same 
dose or at one dose level lower (as detailed in Tables 2−6). 
Table 1 
Overall Dose Modification Guideline for GDC-0032 (taselisib)-
Related Adverse Events 
 
GDC-0032 (taselisib) 
Starting dose 
4 mg daily 
First reduction 
2 mg daily 
Second reduction 
2 mg every other day (QOD) 
No dose reduction is allowed for patients treated at a dose of GDC-0032 
(taselisib) of 2mg QOD – if there is an indication for further dose reduction, the 
patient must permanently discontinue GDC-0032 (taselisib). Dose re-escalation 
is not allowed after a dose reduction. 
NOTE: 
Due to the approximately 40 hour half-life for GDC-0032 
(taselisib), investigators should consider holding GDC-0032 
(taselisib) for certain Grade 2 toxicities until the adverse events 
resolves to Grade ≤ 1 as discussed below (e.g., stomatitis/oral 
mucositis, rash, diarrhea). In addition, certain toxicities can 
occur or worsen within 12 weeks of holding or discontinuing 
GDC-0032 (taselisib) (e.g., pneumonitis, colitis, rash). 
Investigators should follow management guidelines for toxicities as 
described below including administration of topical or systemic 
corticosteroids as appropriate. 
Management of Hyperglycemia 
Metformin is the first antihyperglycemic medication of choice because of the 
lower risk of hypoglycemia with this agent.  Because metformin in some patients 

ECOG-ACRIN 
EAY131-I 
Cancer Research Group 
Version Date: January 25, 2019 
18 
may also cause diarrhea and can be poorly tolerated, other antihyperglycemic 
medications such as sulfonylureas (e.g., glimepiride, glipizide) can be used.  
Extra caution should be used with other drugs such as sulfonylureas because of 
the increased risk for hypoglycemia with these agents. Consultation with an 
endocrinologist can be helpful in managing hyperglycemia.  Management 
guidelines for fasting patients with hyperglycemia are listed below in Table 2 
Table 2: Management of Hyperglycemia 
Grade 
Intervention 
Dose Adjustment 
1 
Initiation of an oral 
anti-hyperglycemic agent 
(e.g., metformin) and 
additional glucose monitoring 
should be considered. 
No change. 
2 
Initiation or increased dose of 
an oral anti-hyperglycemic 
agent (e.g., metformin) and 
additional glucose monitoring 
should be considered. 
Dosing with GDC-0032 (taselisib) 
may either be held or continued 
per Investigator evaluation. 
3, asymptomatic 
Patient should be managed 
as per standard care, 
including implementation of 
additional glucose monitoring 
and initiation and/or increase 
of anti-hyperglycemic therapy 
(e.g., metformin).   
Consideration should be given to 
suspending GDC-0032 (taselisib) 
dosing until the hyperglycemia 
resolves to Grade  2. Dosing with 
GDC-0032 (taselisib) may resume 
at the same dose level or at one 
dose level lower as outlined in 
Table 1 and after discussion with 
the Study Principal Investigator. 
3, symptomatic 
(e.g., blurred vision, 
frequent urination, 
excessive thirst) or 
grade 4 
Patient should be managed 
as per standard care, 
including implementation of 
additional glucose monitoring 
and initiation and/or increase 
of anti-hyperglycemic therapy 
GDC-0032 (taselisib) dosing 
should be suspended until the 
hyperglycemia resolves to Grade  
2. The patient will be discontinued 
from the study if such therapy fails 
to control their hyperglycemia. 
Dosing with GDC-0032 (taselisib) 
may otherwise resume at one dose 
level lower as outlined in Table 1. 
* Based on fasting glucose level 
Management of Pneumonitis 
Patients will be assessed for pulmonary signs and symptoms throughout the 
study (including physical examinations, pulse oximetry, and periodic CT scans).  
Oxygen saturation by pulse oximetry will be measured at every visit as part of the 
assessment of vital signs.  Patients experiencing symptomatic or asymptomatic 
pneumonitis should be treated per standard of care and individual protocol 
guidelines adapted from recommendations by White et al. for the management of 
pneumonitis in cancer patients receiving everolimus10. Use of corticosteroids 
should be considered for symptomatic cases of noninfectious pneumonitis. 
Management guidelines for patients with possible pneumonitis are listed below in 
the Table 3 

ECOG-ACRIN 
EAY131-I 
Cancer Research Group 
Version Date: January 25, 2019 
19 
Table 3: Management of Pneumonitis 
Grade 
Intervention 
Investigations 
Dose Adjustment 
1 
No specific therapy 
required. 
CT scan.  Consider PFTs. 
Repeat CT scan every 6 to 9 
weeks until return to baseline. 
No change. 
2 
Symptomatic only. 
Prescribe 
corticosteroidsa if cough 
is troublesome and 
infectious etiology is 
ruled out. 
CT scan. Repeat CT scan 
every 4 weeks until return to 
baseline. Consider PFTs and 
bronchoscopy. 
Discontinue all study 
treatment until 
improvement to Grade 
 1. If pneumonitis 
improves to grade 1 
and upon completion 
of any corticosteroids, 
resume GDC-0032 
(taselisib) at one dose 
level lower 
Discontinue treatment 
if recovery to Grade  
 1 is not evident 
within 28 days. 
3- 4 
Prescribe corticosteroids 
if infectious etiology is 
ruled out. Taper as 
clinically indicated. 
CT scan. Repeat CT scan 
every 4 weeks until return to 
baseline. Consider PFTs. 
Bronchoscopy is 
recommended. 
Discontinue all study 
treatment regardless 
of the attribution. 
Table modified from White et al10.  
a Suggested corticosteroids include methylprednisolone dose pack or prednisone 60 mg 
daily followed by a taper (e.g., 60 mg  2 days, 40 mg  2 days, 20 mg  2 days, etc.). 
CT  computed tomography; PFT = pulmonary function test 
PFTs include tests for DLCO and room air oxygen saturation at rest (pulse oximetry). 
Repeat CT scans should match schedule for re-staging exams if feasible. 
Management of Rash 
Treatment-related rash, including cases of Grade 3 rash, has occurred in patients 
who received GDC-0032 (taselisib) monotherapy or in combination with other 
anti-cancer drugs. This rash is commonly manifested as maculopapular type with 
or without pruritus, with some having developed desquamation. Rash and other 
dermatological events should be closely monitored. Patients with severe rash 
should be monitored for associated signs and symptoms, such as fever and 
hypotension that may be suggestive of a systemic hypersensitivity reaction. For 
severe rash, hold all study treatment until Grade  1 (see Table 4 below), and 
patients should be treated with supportive therapy per standard of care.  Use of 
topical antihistamine, as well as topical or systemic corticosteroids, may be 
considered 

ECOG-ACRIN 
EAY131-I 
Cancer Research Group 
Version Date: January 25, 2019 
20 
Table 4: Dose Delay and Modification Guidelines for Rash 
Grade 
Intervention 
Dose Adjustment 
Grade 1 
Consider prescribing topical 
corticosteroids a 
Continue dosing at current dose 
and monitor for change in severity. 
Grade 2 
Consider treatment with 
supportive therapy (e.g., topical or 
oral corticosteroids a, b). 
Consider holding GDC-0032 
(taselisib) or reducing to the next 
lower dose if rash is troublesome. 
Grade 3 
or 4 
Consider treatment with 
supportive therapy (e.g., topical or 
oral corticosteroids a, b). 
Consider dermatological 
consultation. 
Consider obtaining photographs 
of rash if permitted by local 
regulations. 
Hold all study treatment until Grade 
 1. 
Restart GDC-0032 (taselisib) at the 
next lower dose upon discussion 
with Overall Principal Investigator, 
or permanently discontinue. 
a Suggested topical steroids include, hydrocortisone 2.5% to face twice daily, 
triamcinolone 0.1% or fluocinonide 0.1% cream to body bid. 
b Suggested oral steroids include methylprednisolone dose pack or prednisone 60 
mg daily followed by a taper (e.g., 60 mg  2 days, 40 mg  2 days, 20 mg  2 days, 
etc.). 
Management of Gastrointestinal Toxicity 
Diarrhea 
Patients should be closely monitored for gastrointestinal symptoms (e.g., nausea, 
vomiting, diarrhea, abdominal pain, stomatitis, and changes in stool, including 
checking for blood in stool if clinically indicated).  Patients should be advised to 
inform the investigator if any diarrhea occurs, even if it is mild. Gastrointestinal 
symptoms should be managed per protocol guidelines. Prompt management of 
diarrhea with antidiarrheal medications should be implemented.  Because of the 
approximately 40 hour half-life of GDC-0032 (taselisib), investigators should hold 
GDC-0032 (taselisib) for Grade ≥ 2 diarrhea. 
Steroid-responsive diarrhea and colitis have been difficult to distinguish in 
patients treated with taselisib. All cases of colitis have been reversible with 
corticosteroid treatment. Prompt initiation of corticosteroids for persistent 
diarrhea despite anti-diarrheal treatment can decrease the severity of the 
diarrhea and prevent the need for hospitalization.  Patients who develop severe 
steroid-responsive diarrhea usually have been on GDC-0032 (taselisib) treatment 
for at least 2 months, with an average onset at 4 to 6 months of treatment.  A 
stool culture is helpful in identifying concurrent infections, and patients have been 
successfully treated with concurrent steroids and appropriate antibiotics, if 
needed. 
If a patient is being treated with corticosteroids, total parenteral nutrition is 
discouraged, as this increases the risk for severe hyperglycemia.  
Discontinuation of non-steroidal inflammatory medications or other medications 
that exacerbate colitis are also recommended during colitis episodes. 
Specific dose modification and management guidelines for diarrhea and colitis 
are provided in Table 5. 

ECOG-ACRIN 
EAY131-I 
Cancer Research Group 
Version Date: January 25, 2019 
21 
Colitis 
For persistent Grade 2 diarrhea that does not resolve or for Grade  3 diarrhea, 
further evaluation should include colitis in the differential diagnosis with the 
appropriate work-up (e.g., abdominal CT scan, endoscopy with biopsy, stool 
cultures for cytomegalovirus, Clostridium difficile, and parasites). Grade  2 
colitis should be managed by interruption of all study treatment. In addition, 
discontinuation of nonsteroidal anti-inflammatory medications or any other 
medications known to exacerbate colitis symptoms should be considered.  If 
noninfectious colitis is suspected, treatment with corticosteroids per institutional 
standard of care is recommended. It is suggested that prednisone (for oral 
administration) or solumedrol (for IV administration) are the corticosteroids of 
choice in the treatment of colitis. For severe symptoms, prednisone 60 mg or 
equivalent may be required to control initial symptoms, and the dose should be 
gradually tapered.  Lower doses of prednisone, oral budesonide, or mesalamine 
(or other 5-aminosalicyclic acid derivatives) may be considered for less severe 
cases of colitis. It has been observed that patients that have developed colitis 
upon GDC-0032 (taselisib) treatment have improved with drug hold and 
coadministration of systemic steroids. 
Specific dose modification and management guidelines for colitis are provided in 
Table 5. 

ECOG-ACRIN 
EAY131-I 
Cancer Research Group 
Version Date: January 25, 2019 
22 
Table 5: 
GDC-0032 (taselisib) Dose Modification and Management Guidelines for 
Diarrhea and Colitis 
Grade of Diarrhea 
Intervention 
Dose Modification 
Grade 1 
Manage per institutional standard of care 
that includes antidiarrheals. a 
For persistent Grade 1 diarrhea occurring 
after Cycle 2, recommend evaluation for 
infectious causes via stool cultureb. For non-
infectious diarrhea, consider colonoscopy to 
evaluate for colitis. 
Continue current dose. 
Grade 2 
Initially manage per institutional standard of 
care until Grade  1.  These include 
antidiarrheals a 
Obtain stool culture for infectious workup b 
Infections (e.g. Clostridium dificile, enteric 
bacteria, CMV) should be treated with the 
appropriate antibiotic 
For persistent Grade 2 non-infectious 
diarrhea lasting longer than 48 hours despite 
treatment with antidiarrheals, treat with oral 
corticosteroids (20-40 mg prednisone QD 
starting dose with taper) or budesonide 9mg 
PO QD. 
If Grade 2 diarrhea does not improve after 
48 hours of corticosteroid treatment, a 
colonoscopy is recommended to evaluate 
for other causes of diarrhea (e.g., CMV 
colitis) 
Hold GDC-0032 (taselisib) and follow 
guidelines below: 
If Grade 2 diarrhea occurred before Cycle 
2, did not require corticosteroid treatment, 
and was an initial episode, resume GDC-
0032 (taselisib) treatment at the same 
dose upon improvement to Grade  1. 
If Grade 2 diarrhea occurred after Cycle 2, 
was a recurrent episode, or improved with 
corticosteroid treatment, resume GDC-
0032 (taselisib) treatment at one dose 
level lower upon improvement to Grade  
1 and after completion of corticosteroid 
treatment. 
For Grade 2 colitis, resume GDC-0032 
(taselisib) treatment at one dose level 
lower upon improvement to Grade  1 and 
after completion of corticosteroid 
treatment. 
Grade 3 (first episode) 
Initially manage with antidiarrheals a. 
Obtain stool culture for infectious workup b. 
For Grade 3 diarrhea or colitis, treat with 
systemic corticosteroids (prednisone 60-80 
mg QD equivalent or solumedrol 16-20 mg 
IV q 8 h to start). Can increase steroid 
dosage if diarrhea does not improve. 
Concurrent infections (e.g., Clostridium 
dificile, enteric bacteria, CMV) should be 
treated with the appropriate antibiotic. 
For patients that do not improve upon 48 
hours of corticosteroid treatment, a 
colonoscopy is recommended to evaluate 
for other causes of diarrhea (e.g. CMV 
colitis) 
Hold GDC-0032 (taselisib). If diarrhea or 
colitis improves to Grade ≤ 1 and upon 
completion of any steroid taper or 
antibiotic treatment, resume GDC-0032 
(taselisib) treatment at one dose level 
lower. 
Grade 3 (recurrent) or 
Grade 4 
Work-up and treatment algorithm as for 
Grade 3 (first episode). 
Permanently discontinue GDC-0032 
(taselisib) 
a Suggested antidiarrheals include the following:  1) loperamide (initial:  4 mg, followed by 2 mg after each lose 
stool, up to 16 mg/day); 2) diphenoxylate and atropine (diphenoxylate 5 mg, four times daily [QID], until control 
achieved (maximum:  20 mg/day), then reduce dose as needed; some patients may be controlled on doses of 5 
mg/day; 3) tincture of opium (6 mg of undiluted opium tincture (10 mg/mL) QID. 
b Non-infectious diarrhea can be diagnosed by stool culture with work-up for various enteric bacteria and C. 
difficile.  Fecal calprotectin is a possible marker for bowel inflammation.  Blood-based CMV PCR test can also be 
used to detect CMV infection. 

ECOG-ACRIN 
EAY131-I 
Cancer Research Group 
Version Date: January 25, 2019 
23 
Management of Stomatitis and Oral Mucositis 
Aggressive mouth care for oral mucositis and stomatitis with mouthwash 
formulations (e.g., combinations of local anesthetic, antihistamine, corticosteroid, 
antacid, antifungal and/or antibiotics) may also be helpful in managing 
symptoms, and it is recommended that these are implemented with early signs of 
dry mouth, Grade 1 mucositis, or Grade 1 stomatitis (see Table 6).  Examples of 
mouth care include rinsing with nonalcoholic mouthwash, flossing after each 
meal, using a mild toothpaste and soft-bristled toothbrush, and avoiding agents 
containing hydrogen peroxide, iodine, and thyme derivatives.  It may also be 
helpful to advise patients to avoid foods that are spicy, acidic, or salty. 
Table 6: 
Dose Delay and Modification Guidelines for Stomatitis and Oral 
Mucositis 
Grade of 
Stomatitis/Mucositis 
Intervention 
Dose Adjustment 
Grade 1 
Aggressive mouth care that 
includes mouthwash 
formulations (e.g., combinations 
of local anesthetic, 
antihistamine, corticosteroid, 
antacid, antifungal and/or 
antibiotics) 
Diet management (e.g., 
avoidance of spicy foods) 
Consider holding 
Taselisib until resolution 
before restarting at same 
dose. 
Grade 2 
Aggressive mouth care that 
includes mouthwash 
formulations (e.g., combinations 
of local anesthetic, 
antihistamine, corticosteroid, 
antacid, antifungal and/or 
antibiotics) 
Diet management (e.g., 
avoidance of spicy foods) 
Hold Taselisib and 
manage until Grade  
 1 then restart Taselisib 
at the same dose. 
If Grade 2 stomatitis/oral 
mucositis recurs, hold 
Taselisib until Grade  
 1 and restart Taselisib 
at the next lower dose. 
Grade 3 or 4 
Aggressive mouth care that 
includes mouthwash 
formulations (e.g., combinations 
of local anesthetic, 
antihistamine, corticosteroid, 
antacid, antifungal and/or 
antibiotics) 
Diet management (e.g., 
avoidance of spicy foods) 
Hold Taselisib and 
manage until Grade  
 1 then restart Taselisib 
at the next lower dose. 
For Grade 4 event, 
consider permanent 
discontinuation of 
Taselisib. 

ECOG-ACRIN 
EAY131-I 
Cancer Research Group 
Version Date: January 25, 2019 
24 
3.5 
Supportive Care  
All supportive measures consistent with optimal patient care will be given 
throughout the study. 
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. 
 

ECOG-ACRIN 
EAY131-I 
Cancer Research Group 
Version Date: January 25, 2019 
25 
4. 
Study Parameters 
4.1 
Therapeutic Parameters for GDC-0032 (taselisib) Treatment 
NOTE: 
In addition to the study parameters listed in the MATCH Master Protocol, the below parameters must also be 
performed for patients receiving GDC-0032 (taselisib) 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 
Cycle 1, Day 
15 
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 
Fasting blood glucose 
X 
XJ 
 XL 
 
 
 
Radiologic evaluationD 
X 
 
 
 XD 
 
 XF 
-HCGC 
X 
 
 
 
 
 
Toxicity AssessmentG 
 
X 
 
 
X 
 XF 
Pill Count/DiaryH 
 
X 
 
 
X 
 
ECGK 
X 
 XI 
 
 
 
 
Tumor biopsy and blood sample for MATCH Master 
ProtocolE 
 
 
 
X 
X 
 
A. History and physical, including vital signs, pulse oximetry, 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, phosphorus, potassium,  SGOT[AST], SGPT[ALT], sodium, 
magnesium and serum tumor markers (including LDH, PSA if appropriate). CBC w/diff, platelets and serum chemistries should be performed 
fasting 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 
Rev. 5/16 
Rev. 12/16 
Rev. 3/17 
Rev. Add13 

ECOG-ACRIN 
EAY131-I 
Cancer Research Group 
Version Date: January 25, 2019 
26 
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 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. 
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. 
L. Fasting glucose can be drawn day 15 ± 3 days and can be drawn at a local lab.  
NOTE: Please provide clear documentation that the glucose test was conducted at a fasting state. 
 

ECOG-ACRIN 
EAY131-I 
Cancer Research Group 
Version Date: January 25, 2019 
27 
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. 
Rev. 12/16 
Rev. 3/17 
Rev. Add13 

ECOG-ACRIN 
EAY131-I 
Cancer Research Group 
Version Date: January 25, 2019 
28 
5.1 
GDC-0032 (NSC #778795) 
5.1.1 
Other Names  
Taselisib, RG7606 
5.1.2 
Classification  
PI3K inhibitor 
5.1.3 
Mode of Action  
Inhibition of PI3K pathway components such as Akt, PRAS40, and 
S6, resulting in G1 arrest and apoptosis. 
5.1.4 
Storage and Stability  
Storage:  GDC-0032 tablets should not be stored above 25ºC.  
Stability:  Shelf-life surveillance of the intact bottles is ongoing. 
If a storage temperature excursion is identified, promptly return GDC-
0032 (taselisib) to ambient 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  
Two 2-mg GDC-0032 tablets will be administered orally once a day on 
a continuous daily dosing schedule. 
5.1.6 
How Supplied  
Genentech supplies and PMB, CTEP, DCTD distributes GDC-0032 as 
white, film- coated, immediate-release 2 mg tablets.  The tablet 
formulation consists of GDC-0032 active, lactose monohydrate, 
microcrystalline cellulose, croscarmellose sodium, magnesium 
stearate, and Opadry 2 white film-coating. The film-coating consists of 
polyvinyl alcohol-part hydrolyzed, titanium dioxide, polyethylene glycol 
3350, and talc.  Each bottle contains 30 film-coated tablets. 
5.1.7 
Route of Administration  
GDC-0032 is taken orally, and may be taken with or without food. 
5.1.8 
Method of Administration 
GDC-0032 may be taken with or without food. 
5.1.9 
Incompatibilities  
GDC-0032 is metabolized via CYP3A4/5. GDC-0032 should not be 
administered with strong CYP3A4/5 inhibitors/inducers and 
administered with caution when combined with moderate CYP3A4/5 
inhibitors/inducers.  No drug-drug interactions were observed in 
cancer patients with the following CYP3A4 substrates: midazolam, 
letrozole, or fulvestrant. Grapefruit and grapefruit juice should be 
avoided due to the risk of increased GDC-0032 exposure. 
Avoid grapefruit/ grapefruit juice and Seville oranges while 
participating in this trial. 
Rev. 12/16 

ECOG-ACRIN 
EAY131-I 
Cancer Research Group 
Version Date: January 25, 2019 
29 
In vitro studies showed that taselisib was a substrate of P-glycoprotein 
(P-gp) and breast cancer resistance protein (BCRP). In vitro testing 
also found GDC-0032 to be an inhibitor of OATP1B1, OATP1B3, 
OCT1, OCT2 and OAT3. GDC-0032 was also found to not be a potent 
inhibitor of CYP isoforms 1A2, 2B6, 2C8, 2C9, 2C19, 2D6 or 3A4/5 or 
transporters P-gp, BCRP or OAT1. 
5.1.10 
Side Effects  
See Section 3.3 for side effects. 
5.1.11 
Nursing/Patient Implications  
• 
Hyperglycemia (Grades 1-4) was reported in approximately 32% 
of the patients who received GDC-0032 as a single agent. 
Patients with diabetes mellitus requiring insulin therapy should be 
excluded from studies of GDC-0032. Glucose levels should be 
carefully monitored at baseline and during study per individual 
protocol guidelines. Patients should be instructed to report 
symptoms associated with hyperglycemia, such as thirst, frequent 
urination, and blurred vision. Anti-hyperglycemic agents should be 
used to control severe hyperglycemia per institutional standard of 
care. 
• 
Non-infectious pneumonitis has been observed in patients treated 
with GDC-0032 QD, with onset at approximately Day 66-167 days 
post dosing. Patients who require any daily supplemental oxygen 
should not be recruited for the study. 
• 
Reproductive Risks: 
• 
Women of child bearing potential and male patients should 
continue contraceptive measures for 4 months after the last 
dose of GDC-0032. 
 

ECOG-ACRIN 
EAY131-I 
Cancer Research Group 
Version Date: January 25, 2019 
30 
6. 
Translational Studies 
Please refer to the MATCH Master Protocol for information on the Translational Studies.  
7. 
References 
1. 
Cantley LC. The phosphoinositide 3-kinase pathway. Science. 
2002;296(5573):1655-1657. 
2. 
Guertin DA, Sabatini DM. Defining the role of mTOR in cancer. Cancer Cell. 
2007;12(1):9-22. 
3. 
Bachman KE, Argani P, Samuels Y, et al. The PIK3CA gene is mutated with high 
frequency in human breast cancers. Cancer Biol Ther. 2004;3(8):772-775. 
4. 
Massion PP, Taflan PM, Shyr Y, et al. Early involvement of the phosphatidylinositol 
3-kinase/Akt pathway in lung cancer progression. Am J Respir Crit Care Med. 
2004;170(10):1088-1094. 
5. 
Shayesteh L, Lu Y, Kuo WL, et al. PIK3CA is implicated as an oncogene in ovarian 
cancer. Nat Genet. 1999;21(1):99-102. 
6. 
Burke JE, Perisic O, Masson GR, Vadas O, Williams RL. Oncogenic mutations 
mimic and enhance dynamic events in the natural activation of phosphoinositide 3-
kinase p110alpha (PIK3CA). Proc Natl Acad Sci U S A. 2012;109(38):15259-
15264. 
7. 
Gymnopoulos M, Elsliger MA, Vogt PK. Rare cancer-specific mutations in PIK3CA 
show gain of function. Proc Natl Acad Sci U S A. 2007;104(13):5569-5574. 
8. 
Hon WC, Berndt A, Williams RL. Regulation of lipid binding underlies the activation 
mechanism of class IA PI3-kinases. Oncogene. 2012;31(32):3655-3666. 
9. 
Murugan AK, Hong NT, Fukui Y, Munirajan AK, Tsuchida N. Oncogenic mutations 
of the PIK3CA gene in head and neck squamous cell carcinomas. Int J Oncol. 
2008;32(1):101-111. 
10. Rudd ML, Price JC, Fogoros S, et al. A unique spectrum of somatic PIK3CA 
(p110alpha) mutations within primary endometrial carcinomas. Clin Cancer Res. 
2011;17(6):1331-1340. 
11. Janku F, Hong DS, Fu S, et al. Assessing PIK3CA and PTEN in early-phase trials 
with PI3K/AKT/mTOR inhibitors. Cell Rep. 2014;6(2):377-387. 
12. Han SY, Kato H, Kato S, et al. Functional evaluation of PTEN missense mutations 
using in vitro phosphoinositide phosphatase assay. Cancer Res. 
2000;60(12):3147-3151. 
13. Rodriguez-Escudero I, Oliver MD, Andres-Pons A, Molina M, Cid VJ, Pulido R. A 
comprehensive functional analysis of PTEN mutations: implications in tumor- and 
autism-related syndromes. Hum Mol Genet. 2011;20(21):4132-4142. 
14. Edgar KA, Wallin JJ, Berry M, et al. Isoform-specific phosphoinositide 3-kinase 
inhibitors exert distinct effects in solid tumors. Cancer Res. 2010;70(3):1164-1172. 
15. Jia S, Liu Z, Zhang S, et al. Essential roles of PI(3)K-p110beta in cell growth, 
metabolism and tumorigenesis. Nature. 2008;454(7205):776-779. 

ECOG-ACRIN 
EAY131-I 
Cancer Research Group 
Version Date: January 25, 2019 
31 
16. Wee S, Wiederschain D, Maira SM, et al. PTEN-deficient cancers depend on 
PIK3CB. Proc Natl Acad Sci U S A. 2008;105(35):13057-13062. 
17. Juric D, Castel P, Griffith M, et al. Convergent loss of PTEN leads to clinical 
resistance to a PI(3)Kalpha inhibitor. Nature. 2015;518(7538):240-244. 
18. 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. 2009;69(1):143-150. 
19. She QB, Halilovic E, Ye Q, et al. 4E-BP1 is a key effector of the oncogenic 
activation of the AKT and ERK signaling pathways that integrates their function in 
tumors. Cancer Cell. 2010;18(1):39-51. 
20. White DA, Camus P, Endo M, et al. Noninfectious pneumonitis after everolimus 
therapy for advanced renal cell carcinoma. Am J Respir Crit Care Med. 
2010;182(3):396-403. 
 

ECOG-ACRIN 
EAY131-I 
Cancer Research Group 
Version Date: January 25, 2019 
32 
Molecular Analysis for Therapy Choice (MATCH) 
MATCH Treatment Subprotocol I: GDC-0032 (taselisib) 
Appendix I 
 
Patient Pill Calendar 
Storage: Store at Room Temperature 
Pill Calendar Directions 
1. Take your scheduled dose of two 2-mg tablets, which will be administered orally 
once a day, at approximately the same time each day. 
2. If you forget to take your dose at the scheduled time, you may take it within 6 hours 
after the usual time. If the dose is not taken within 6 hours of the usual time, the 
missed tablets will not be taken later. Instead, resume your dose the next day. 
3. Please bring the empty bottle or any leftover tablets and your pill calendar to your 
next clinic visit. 
4. Tablets will be taken once a day, at approximately the same time each day, with a 
full glass of water, with or without food. 
5. Swallow tablets whole, do not crush or chew tablets. 
 
 
Rev. 12/16 
Rev. 3/17 

ECOG-ACRIN 
EAY131-I 
Cancer Research Group 
Version Date: January 25, 2019 
33 
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. 
GDC-0032 (taselisib) 
DAY  
Date 
Time tablets 
taken 
Number of 
tablets 
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: _____________

ECOG-ACRIN 
EAY131-I 
Cancer Research Group 
Version Date: January 25, 2019 
34 
Molecular Analysis for Therapy Choice (MATCH) 
MATCH Treatment Subprotocol I: GDC-0032 (taselisib) 
Appendix II 
 
Actionable Mutations for Sub-Protocol EAY131-I 
 
A. Inclusion variants 
Gene Name 
Variant ID 
Variant Type 
Level of Evidence Code 
Variant Description 
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 
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 
Rev. 5/16 
Rev. Add13 
Rev. 12/16 

ECOG-ACRIN 
EAY131-I 
Cancer Research Group 
Version Date: January 25, 2019 
35 
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 
B. Exclusion variants 
MATCHBOX also was implemented with a function to identify any deleterious mutations in 
PTEN as exclusion variants (LOE code = 3). 
Patients with negative PTEN IHC staining are not eligible (LOE code = 3). 
Gene Name 
Variant ID 
Variant 
Type 
Level of Evidence 
Code 
Variant Description 
PTEN 
COSM86058 
SNV 
3 
p.A34D 
PTEN 
COSM5223 
SNV 
3 
p.M35R 
PTEN 
COSM5135 
SNV 
3 
p.G36R 
PTEN 
OM1539 
SNV 
3 
p.N48K 
PTEN 
MCH13 
SNV 
3 
p.H61D 
PTEN 
MCH14 
SNV 
3 
p.Y68D 
PTEN 
COSM5264 
SNV 
3 
p.D92A 
PTEN 
COSM35759 
SNV 
3 
p.D92E 
PTEN 
COSM125653 
SNV 
3 
p.D92E 
PTEN 
COSM5099 
SNV 
3 
p.D92G 
PTEN 
COSM23566 
SNV 
3 
p.D92H 
PTEN 
COSM5236 
SNV 
3 
p.D92V 
PTEN 
COSM5283 
SNV 
3 
p.H93D 
PTEN 
COSM5043 
SNV 
3 
p.H93Y 
PTEN 
COSM5265 
SNV 
3 
p.P96Q 
PTEN 
COSM5273 
SNV 
3 
p.A121E 
PTEN 
COSM5234 
SNV 
3 
p.I122S 
PTEN 
COSM921088 
SNV 
3 
p.H123D 
PTEN 
COSM5082 
SNV 
3 
p.K125E 
PTEN 
COSM5041 
SNV 
3 
p.A126V 
PTEN 
COSM5143 
SNV 
3 
p.G127E 
PTEN 
COSM28917 
SNV 
3 
p.G129E 
PTEN 
COSM5276 
SNV 
3 
p.G129V 
PTEN 
COSM246853 
SNV 
3 
p.G129R 
PTEN 
COSM5104 
SNV 
3 
p.T131I 
PTEN 
COSM5144 
SNV 
3 
p.Y155C 
PTEN 
COSM5114 
SNV 
3 
p.G165E 
PTEN 
COSM249877 
SNV 
3 
p.G165V 

ECOG-ACRIN 
EAY131-I 
Cancer Research Group 
Version Date: January 25, 2019 
36 
PTEN 
MCH20 
SNV 
3 
p.S170R 
PTEN 
MCH17 
SNV 
3 
p.L181P 
PTEN 
MCH18 
SNV 
3 
p.V343E 
PTEN 
COSM5133 
SNV 
3 
p.Y16C 
PTEN 
COSM5247 
SNV 
3 
p.Y27S 
PTEN 
COSM5042 
SNV 
3 
p.H61R 
PTEN 
COSM5036 
SNV 
3 
p.Y68H 
PTEN 
COSM5102 
SNV 
3 
p.C71Y 
PTEN 
COSM5266 
SNV 
3 
p.C105F 
PTEN 
COSM5212 
SNV 
3 
p.D107Y 
PTEN 
COSM5106 
SNV 
3 
p.L112P 
PTEN 
MCH15 
SNV 
3 
p.L112R 
PTEN 
COSM5214 
SNV 
3 
p.A121P 
PTEN 
COSM921089 
SNV 
3 
p.C124R 
PTEN 
COSM5224 
SNV 
3 
p.C124S 
PTEN 
COSM5219 
SNV 
3 
p.R130G 
PTEN 
COSM5033 
SNV 
3 
p.R130Q 
PTEN 
COSM5216 
SNV 
3 
p.R130L 
PTEN 
COSM5044 
SNV 
3 
p.V133I 
PTEN 
COSM12734 
SNV 
3 
p.C136Y 
PTEN 
COSM5091 
SNV 
3 
p.G165R 
PTEN 
COSM5045 
SNV 
3 
p.S170N 
PTEN 
COSM5089 
SNV 
3 
p.R173C 
PTEN 
COSM5039 
SNV 
3 
p.R173H 
PTEN 
MCH16 
SNV 
3 
p.R173P 
PTEN 
COSM5221 
SNV 
3 
p.Y174N 
PTEN 
COSM5220 
SNV 
3 
p.G251C 
PTEN 
COSM5255 
SNV 
3 
p.F341V 
PTEN 
COSM5213 
SNV 
3 
p.L345Q 
PTEN 
MCH21 
SNV 
3 
p.S170R 
PTEN 
MCH22 
SNV 
3 
p.S170R 
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 

ECOG-ACRIN 
EAY131-I 
Cancer Research Group 
Version Date: January 25, 2019 
37 
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 
KRAS 
COSM516 
SNV 
2 
p.G12C 
KRAS 
COSM518 
SNV 
2 
p.G12R 
KRAS 
COSM517 
SNV 
2 
p.G12S 
KRAS 
COSM19404 
SNV 
3 
p. A146T 

ECOG-ACRIN 
EAY131-I 
Cancer Research Group 
Version Date: January 25, 2019 
38 
Molecular Analysis for Therapy Choice (MATCH) 
MATCH Treatment Subprotocol I: GDC-0032 (taselisib) 
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, GDC-0032 (taselisib).  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: 
GDC-0032 (taselisib) interacts with a certain specific enzymesenzyme in your liver* and certain 
transport proteins that help move drugs in and out of cells.** 
• 
* The enzyme in question is CYP3A4.  GDC-0032 (taselisib) is metabolized by this 
enzyme and may be affected by other drugs that inhibit or induce this enzyme.   
• 
** The proteins in question are P-glycoprotein (P-gp) and breast cancer resistance 
protein (BCRP).  GDC-0032 (taselisib) is a substrate of these transporters and is 
moved in and out of cells/organs by these transport proteins.  GDC-0032 (taselisib) is 
an inhibitor of OAT1B1, OAT1B3, OCT1, OCT2, and OAT3 and may affect transport 
of other drugs in and out of cells. 
To the patient: Take this paper with you to your medical appointments and keep the 
attached information card in your wallet.   
GDC-0032 (taselisib) 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:  
GDC-0032 (taselisib) must be used very carefully with other medicines that use certain liver 
enzymes or transport proteins to be effective or to be cleared from your system.  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 
CYP3A4, P-gp or BCRP. 
• 
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.  
• 
Do not drink or eat grapefruit, grapefruit /juice andor Seville oranges 

ECOG-ACRIN 
EAY131-I 
Cancer Research Group 
Version Date: January 25, 2019 
39 
• 
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 GDC-0032 (taselisib).  This 
clinical trial is sponsored by the NCI.  GDC-0032 
(taselisib) 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.  
➢ Do not drink or eat grapefruit/juice or Seville 
oranges. 
GDC-0032 (taselisib) interacts with a specific liver enzyme 
called CYP3A4/5, transport proteins P-gp, BCRP, 
OATP1B1, OATP1B3, OCT1, OCT2 and OAT3and must 
be used very carefully with other medicines that interact 
with these enzymes and transporters.  
➢ 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 CYP3A4/5 
or transporters P-gp and BCRP. GDC-0032 (taselisib) 
can inhibit transporters OATP1B1, OATP1B3, OCT1, 
OCT2 and OAT3 that may affect other drugs.  
➢ 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  
_________________________________.