A Study of Ipatasertib (GDC-0068) in Combination With Paclitaxel as Neoadjuvant Treatment for Participants With Early Stage Triple Negative Breast Cancer

• Sponsor: Genentech, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02301988
• Collaborator: SOLTI Breast Cancer Research Group (Other)
• Enrollment: 151
• Locations: 42
• Arms: 2
• Actual Duration (Months): 29.5
• Patients Per Site: 3.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a randomized, double-blind, placebo-controlled, multicenter, pre-operative Phase II study designed to estimate the efficacy of ipatasertib combined with paclitaxel chemotherapy versus placebo combined with paclitaxel chemotherapy in women with Stage Ia - IIIa triple-negative breast adenocarcinoma. The anticipated time on study treatment is 12 weeks.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Ipatasertib; Drug: Paclitaxel; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 151 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase II Randomized, Double-Blind, Study of Ipatasertib (GDC-0068), an Inhibitor to AKT, in Combination With Paclitaxel as Neoadjuvant Treatment for Patients With Early Stage Triple Negative Breast Cancer
• Actual Study Start Date: Feb 17, 2015
• Actual Primary Completion Date: Aug 2, 2017
• Actual Study Completion Date: Aug 2, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ipatasertib + Paclitaxel Participants will receive ipatasertib orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel intravenous (IV) infusion every week (QW) for 3 cycles (12 total doses).	Drug: Ipatasertib; Ipatasertib will be administered at a dose of 400 milligrams (mg) orally daily on Days 1-21 of each 28-day cycle for 3 cycles.; Other Names: GDC-0068 ; Drug: Paclitaxel; Paclitaxel will be administered at a dose of 80 milligrams per square meter (mg/m^2) as IV infusion QW for 3 cycles.
Placebo Comparator: Placebo + Paclitaxel Participants will receive placebo (matching to ipatasertib) orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel IV infusion QW for 3 cycles (12 total doses).	Drug: Paclitaxel; Paclitaxel will be administered at a dose of 80 milligrams per square meter (mg/m^2) as IV infusion QW for 3 cycles.; Drug: Placebo; Participants will receive placebo (matching to ipatasertib) orally daily on Days 1-21 of each 28-day cycle for 3 cycles.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Pathological Complete Response (pCR) in Breast and Axilla as Defined by ypT0/Tis ypN0 in the American Joint Committee on Cancer Staging System (in All Participants) [Surgery visit (at approximately Weeks 14 to 19)]

   pCR was defined by ypT0/Tis ypN0 in the American Joint Committee on Cancer (AJCC) Staging System with the following determination for breast and axilla by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue and N0: no cancer found in the lymph nodes.

2. Percentage of Participants With pCR in Breast and Axilla as Defined by ypT0/Tis ypN0 in the American Joint Committee on Cancer Staging System (in Participants Who Have Phosphatase and Tensin Homolog [PTEN]-Low Tumors) [Surgery visit (at approximately Weeks 14 to 19)]

   pCR was defined by ypT0/Tis ypN0 in the AJCC Staging System with the following determination for breast and axilla by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue and N0: no cancer found in the lymph nodes.

Secondary Outcome Measures

1. Percentage of Participants With pCR in Breast as Defined by ypT0/Tis in the American Joint Committee on Cancer Staging System (in All Participants) [Surgery visit (at approximately Weeks 14 to 19)]

   pCR was defined by ypT0/Tis in the AJCC Staging System with the following determination for breast by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue.

2. Percentage of Participants With pCR in Breast as Defined by ypT0/Tis in the American Joint Committee on Cancer Staging System (in Participants Who Have PTEN-low Tumors) [Surgery visit (at approximately Weeks 14 to 19)]

   pCR was defined by ypT0/Tis in the AJCC Staging System with the following determination for breast by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue.

3. Percentage of Participants With Objective Tumor Response by Magnetic Resonance Imaging (MRI), As Assessed by Investigator Per the Modified Response Evaluation Criteria in Solid Tumors (RECIST) (in All Participants) [Screening up to disease progression or death (assessed at screening, pre-surgical visit [approximately Weeks 10-12], early termination visit [up to Week 16])]

   Objective tumor response (OR) was based on criteria related to changes in size of target lesions according to modified RECIST. Target lesions were selected on the basis of their size (lesions with the longest diameter) as well as the feasibility of reproducible repeated measurements. OR was the sum of complete response (CR) and partial response (PR). CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

4. Percentage of Participants With Objective Tumor Response by MRI, As Assessed by Investigator Per Modified RECIST (in Participants Who Have PTEN-low Tumors) [Screening up to disease progression or death (assessed at screening, pre-surgical visit [approximately Weeks 10-12], early termination visit [up to Week 16])]

   ORR was based on criteria related to changes in size of target lesions according to modified RECIST. Target lesions were selected on the basis of their size (lesions with the longest diameter) as well as the feasibility of reproducible repeated measurements. ORR was the sum of complete response (CR) and partial response (PR). CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

5. Percentage of Participants With pCR in Breast and Axilla as Defined by ypT0/Tis ypN0 in the American Joint Committee on Cancer Staging System (in Participants Who Are Akt Diagnostic Positive [Dx+]) [Surgery visit (at approximately Weeks 14 to 19)]

   pCR was defined by ypT0/Tis ypN0 in the AJCC Staging System with the following determination for breast and axilla by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue and N0: no cancer found in the lymph nodes.

6. Percentage of Participants With pCR in Breast as Defined by ypT0/Tis in the American Joint Committee on Cancer Staging System (in Participants Who Are Akt Dx+) [Surgery visit (at approximately Weeks 14 to 19)]

   pCR was defined by ypT0/Tis in the AJCC Staging System with the following determination for breast by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue.

7. Percentage of Participants With pCR According to American Joint Committee on Cancer Staging System, by Breast Cancer Subtype [Surgery visit (at approximately Weeks 14 to 19)]

   pCR was defined by ypT0/Tis in the AJCC Staging System with the following determination for breast subtypes by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue. The intrinsic molecular subtypes of breast cancer included here are luminal A (LumA), Her-2, basal-like, normal and unknown.

8. Percentage of Participants With Response to Undergoing Breast Conserving Surgery (BCS) Among Participants With T2 or T3 Tumors [Surgery visit (at approximately Weeks 14 to 19)]

   After neoadjuvant treatment, the number of patients who is appropriate for breast conserving surgery is reported as a measure of efficacy of the treatment to shrink the tumor enough for patients to benefit from less aggressive surgical management. Breast-conserving surgery was defined as removal of part of the breast tissue during surgery. T2 or T3 in the AJCC Staging System were defined as follows: T2: tumor was more than 2 centimeter (cm) but no more than 5 cm across; T3: tumor was larger than 5 cm across.

9. Percentage of Participants With Response to Conversion to BCS Among Participants With T2 or T3 Tumors [From screening to surgery visit (at approximately Weeks 14 to 19)]

   After neoadjuvant treatment, the number of patients who is appropriate for breast conserving surgery is reported as a measure of efficacy of the treatment to shrink the tumor enough for patients to benefit from less aggressive surgical management. Breast-conserving surgery was defined as removal of part of the breast tissue during surgery. T2 or T3 in the AJCC Staging System were defined as follows: T2: tumor was more than 2 centimeter (cm) but no more than 5 cm across; T3: tumor was larger than 5 cm across.

10. Percentage of Participants With Adverse Events [Screening up to Week 24]

    An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

11. Plasma Concentrations of Ipatasertib on Day 1 and Day 8 [0.5 and 4 hours post dose on Day 1 of Cycle 1, 166 and 170 hours post dose from Day 1 of Cycle 1 (Cycle length = 28 days)]

    Plasma samples for pharmacokinetic characterization was collected at various timepoints in all participants.

12. Minimum Observed Plasma Concentration (Cmin) of Ipatasertib [0.5 and 4 hours post dose on Day 1 of Cycle 1, 166 and 170 hours post dose from Day 1 of Cycle 1 (Cycle length = 28 days)]

    Plasma samples for pharmacokinetic characterization was collected on Day 1 and Day 8 in all participants.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Premenopausal or postmenopausal women

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Histologically documented, Stage Ia to operable Stage IIIa, triple-negative carcinoma of the breast with primary tumor greter than or equal to (>/=) 1.5 centimeters (cm) in largest diameter (cT1-3) by MRI

• Adequate hematologic and organ function within 14 days before the first study treatment

• Availability of tumor tissue from formalin-fixed, paraffin-embedded (FFPE) core biopsy of breast primary tumor

• For female participants of childbearing potential, agreement to use highly effective form(s) of contraception for the duration of the study and for at least 6 months after last dose of study treatment

Exclusion Criteria:

• Known human epidermal growth factor 2 (HER2)-positive, estrogen receptor (ER)-positive, or progesterone receptor (PgR)-positive breast cancer

• Any prior treatment for the current primary invasive breast cancer

• Participants with cT4 or cN3 stage breast tumors

• Metastatic (Stage IV) breast cancer

• Bilateral invasive breast cancer

• Multicentric breast cancer

• Any disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the participant at high risk from treatment complications

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Oncology Associates, PC-CASA	Tucson	Arizona	United States	85704
2	Sansum Medical Clinic, Inc.	Santa Barbara	California	United States	93105
3	Rocky Mountain Cancer Center - Lakewood (West)	Lakewood	Colorado	United States	80228
4	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
5	Mass General/North Shore Cancer	Danvers	Massachusetts	United States	01923
6	Nebraska Cancer Specialists; Oncology Hematology West, PC	Omaha	Nebraska	United States	68130
7	Carolinas Healthcare System	Charlotte	North Carolina	United States	28208
8	Northwest Cancer Specialists - Portland (NE Hoyt St)	Portland	Oregon	United States	97213
9	Roper Bon Secours St. Francis Cancer Center	Charleston	South Carolina	United States	29414
10	Texas Oncology	Austin	Texas	United States	78705
11	Texas Oncology Cancer Center	Austin	Texas	United States	78731
12	Texas Oncology - Baylor Charles A. Sammons Cancer Center	Dallas	Texas	United States	75246
13	Texas Oncology - Houston (Gessner)	Houston	Texas	United States	77024
14	Texas Oncology-Tyler	Irving	Texas	United States	75063
15	South Texas Cancer Center - McAllen	McAllen	Texas	United States	78503
16	Northwest Medical Specialties, PLLC	Tacoma	Washington	United States	98405
17	IPO de Lisboa; Servico de Oncologia Medica	Lisboa		Portugal	1099-023
18	Hospital Beatriz Angelo; Departamento de Oncologia	Loures		Portugal	2674-514
19	IPO do Porto; Servico de Oncologia Medica	Porto		Portugal	4200-072
20	Hospital Universitario Son Espases	Palma De Mallorca	Islas Baleares	Spain	07014
21	Hospital Son Llatzer; Servicio de Oncologia	Palma de Mallorca	Islas Baleares	Spain	07198
22	Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia	Santiago de Compostela	LA Coruña	Spain	15706
23	Hospital Universitari de Lleida Arnau de Vilanova	Lleida	Lerida	Spain	25198
24	Hospital Universitario Fundación Alcorcón	Alcorcón (Madrid)	Madrid	Spain	28922
25	Hospital Rey Juan Carlos; Pharmacy	Mostoles	Madrid	Spain	28933
26	Hospital Regional Universitario Carlos Haya; hospital Materno Infantil, servicio de Farmacia	Málaga	Malaga	Spain	29011
27	Hospital Universitario Virgen Macarena	Seville	Sevilla	Spain	41071
28	Hospital Universitari Sant Joan de Reus; Servicio de Oncologia	Reus	Tarragona	Spain	43204
29	Hospital Univ Vall d'Hebron; Servicio de Oncologia	Barcelona		Spain	08035
30	Institut Catala d Oncologia Hospital Duran i Reynals	Barcelona		Spain	08908
31	Hospital San Pedro De Alcantara; Servicio de Oncologia	Caceres		Spain	10003
32	Hospital Provincial de Castellon; Servicio de Oncologia	Castellon		Spain	12002
33	Hospital Universitari de Girona Dr. Josep Trueta; Servicio de Oncologia	Girona		Spain	17007
34	Centro Oncologico MD Anderson International Espana	Madrid		Spain	28033
35	Fundacion Jimenez Diaz; Servicio de Oncologia	Madrid		Spain	28040
36	Hospital Universitario Clínico San Carlos	Madrid		Spain	28040
37	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid		Spain	28041
38	Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica	Madrid		Spain	28050
39	Hospital Quiron de Madrid; Servicio de Oncologia	Madrid		Spain	28223
40	Hospital Universitario de Fuenlabrada; Servicio de Oncologia	Madrid		Spain	28943
41	Hospital Virgen del Rocio	Sevilla		Spain	41013
42	Hospital Clinico Universitario; Oncologia	Valencia		Spain	46010

Sponsors and Collaborators

• Genentech, Inc.
• SOLTI Breast Cancer Research Group

Investigators

• Study Director: Clinical Trials, Genentech, Inc.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 19, 2016

More Information

Publications

None provided.

• Responsible Party: Genentech, Inc.
• ClinicalTrials.gov Identifier: NCT02301988
• Other Study ID Numbers: GO29505; 2014-003029-16
• First Posted: Nov 26, 2014
• Last Update Posted: Oct 17, 2018
• Last Verified: Sep 1, 2018

• Additional relevant MeSH terms: Breast Neoplasms; Triple Negative Breast Neoplasms; Paclitaxel

Study Results

Participant Flow

Arm/Group Title	Ipatasertib + Paclitaxel	Placebo + Paclitaxel
Arm/Group Description	Participants received ipatasertib orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel intravenous (IV) infusion every week (QW) for 3 cycles (12 total doses).	Participants received placebo (matching to ipatasertib) orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel IV infusion QW for 3 cycles (12 total doses).
Period Title: Overall Study
STARTED	76	75
COMPLETED	66	66
NOT COMPLETED	10	9

Baseline Characteristics

Arm/Group Title	Ipatasertib + Paclitaxel	Placebo + Paclitaxel	Total
Arm/Group Description	Participants received ipatasertib orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel intravenous (IV) infusion every week (QW) for 3 cycles (12 total doses).	Participants received placebo (matching to ipatasertib) orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel IV infusion QW for 3 cycles (12 total doses).	Total of all reporting groups
Overall Participants	76	75	151
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.8 (10.9)	53.8 (12.0)	53.8 (11.5)
Sex: Female, Male (Count of Participants)
Female	76 100%	75 100%	151 100%
Male	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 1.3%	1 0.7%
Native Hawaiian or Other Pacific Islander	1 1.3%	0 0%	1 0.7%
Black or African American	2 2.6%	3 4%	5 3.3%
White	71 93.4%	70 93.3%	141 93.4%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	2 2.6%	1 1.3%	3 2%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Pathological Complete Response (pCR) in Breast and Axilla as Defined by ypT0/Tis ypN0 in the American Joint Committee on Cancer Staging System (in All Participants)
Description	pCR was defined by ypT0/Tis ypN0 in the American Joint Committee on Cancer (AJCC) Staging System with the following determination for breast and axilla by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue and N0: no cancer found in the lymph nodes.
Time Frame	Surgery visit (at approximately Weeks 14 to 19)

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants.

Arm/Group Title	Ipatasertib + Paclitaxel	Placebo + Paclitaxel
Arm/Group Description	Participants received ipatasertib orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel intravenous (IV) infusion every week (QW) for 3 cycles (12 total doses).	Participants received placebo (matching to ipatasertib) orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel IV infusion QW for 3 cycles (12 total doses).
Measure Participants	76	75
Number (95% Confidence Interval) [percentage of participants]	17.1 22.5%	13.3 17.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ipatasertib + Paclitaxel, Placebo + Paclitaxel
	Comments	Unstratified Analysis
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.519
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	3.77
	Confidence Interval	() 95%; -8.99 to 16.54
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% CI for difference in rates were constructed using normal approximation (Wald) with continuity correction.

2. Primary Outcome

Title	Percentage of Participants With pCR in Breast and Axilla as Defined by ypT0/Tis ypN0 in the American Joint Committee on Cancer Staging System (in Participants Who Have Phosphatase and Tensin Homolog [PTEN]-Low Tumors)
Description	pCR was defined by ypT0/Tis ypN0 in the AJCC Staging System with the following determination for breast and axilla by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue and N0: no cancer found in the lymph nodes.
Time Frame	Surgery visit (at approximately Weeks 14 to 19)

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants who have PTEN-low tumors.

Arm/Group Title	Ipatasertib + Paclitaxel	Placebo + Paclitaxel
Arm/Group Description	Participants received ipatasertib orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel intravenous (IV) infusion every week (QW) for 3 cycles (12 total doses).	Participants received placebo (matching to ipatasertib) orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel IV infusion QW for 3 cycles (12 total doses).
Measure Participants	19	16
Number (95% Confidence Interval) [percentage of participants]	15.8 20.8%	12.5 16.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ipatasertib + Paclitaxel, Placebo + Paclitaxel
	Comments	Unstratified analysis
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7817
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference in response rates
	Estimated Value	3.29
	Confidence Interval	(2-Sided) 95%; -25.52 to 32.10
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% CI for difference in rates were constructed using normal approximation (Wald) with continuity correction.

3. Secondary Outcome

Title	Percentage of Participants With pCR in Breast as Defined by ypT0/Tis in the American Joint Committee on Cancer Staging System (in All Participants)
Description	pCR was defined by ypT0/Tis in the AJCC Staging System with the following determination for breast by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue.
Time Frame	Surgery visit (at approximately Weeks 14 to 19)

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants.

Arm/Group Title	Ipatasertib + Paclitaxel	Placebo + Paclitaxel
Arm/Group Description	Participants received ipatasertib orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel intravenous (IV) infusion every week (QW) for 3 cycles (12 total doses).	Participants received placebo (matching to ipatasertib) orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel IV infusion QW for 3 cycles (12 total doses).
Measure Participants	76	75
Number (95% Confidence Interval) [percentage of participants]	22.4 29.5%	14.7 19.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ipatasertib + Paclitaxel, Placebo + Paclitaxel
	Comments	Unstratified analysis
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2234
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	7.70
	Confidence Interval	(2-Sided) 95%; -5.95 to 21.35
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% CI for difference in rates were constructed using normal approximation (Wald) with continuity correction.

4. Secondary Outcome

Title	Percentage of Participants With pCR in Breast as Defined by ypT0/Tis in the American Joint Committee on Cancer Staging System (in Participants Who Have PTEN-low Tumors)
Description	pCR was defined by ypT0/Tis in the AJCC Staging System with the following determination for breast by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue.
Time Frame	Surgery visit (at approximately Weeks 14 to 19)

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants who have PTEN-low tumors.

Arm/Group Title	Ipatasertib + Paclitaxel	Placebo + Paclitaxel
Arm/Group Description	Participants received ipatasertib orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel intravenous (IV) infusion every week (QW) for 3 cycles (12 total doses).	Participants received placebo (matching to ipatasertib) orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel IV infusion QW for 3 cycles (12 total doses).
Measure Participants	19	16
Number (95% Confidence Interval) [percentage of participants]	15.8 20.8%	18.8 25.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ipatasertib + Paclitaxel, Placebo + Paclitaxel
	Comments	Unstratified analysis
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8169
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference in response rates
	Estimated Value	-2.96
	Confidence Interval	(2-Sided) 95%; -33.91 to 27.99
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% CI for difference in rates were constructed using normal approximation (Wald) with continuity correction.

5. Secondary Outcome

Title	Percentage of Participants With Objective Tumor Response by Magnetic Resonance Imaging (MRI), As Assessed by Investigator Per the Modified Response Evaluation Criteria in Solid Tumors (RECIST) (in All Participants)
Description	Objective tumor response (OR) was based on criteria related to changes in size of target lesions according to modified RECIST. Target lesions were selected on the basis of their size (lesions with the longest diameter) as well as the feasibility of reproducible repeated measurements. OR was the sum of complete response (CR) and partial response (PR). CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Time Frame	Screening up to disease progression or death (assessed at screening, pre-surgical visit [approximately Weeks 10-12], early termination visit [up to Week 16])

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants.

Arm/Group Title	Ipatasertib + Paclitaxel	Placebo + Paclitaxel
Arm/Group Description	Participants received ipatasertib orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel intravenous (IV) infusion every week (QW) for 3 cycles (12 total doses).	Participants received placebo (matching to ipatasertib) orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel IV infusion QW for 3 cycles (12 total doses).
Measure Participants	76	75
Number (95% Confidence Interval) [percentage of participants]	67.1 88.3%	56.0 74.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ipatasertib + Paclitaxel, Placebo + Paclitaxel
	Comments	Unstratified analysis
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1607
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference in response rate
	Estimated Value	11.11
	Confidence Interval	() 95%; -5.64 to 27.85
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% CI for difference in rates were constructed using normal approximation (Wald) with continuity correction.

6. Secondary Outcome

Title	Percentage of Participants With Objective Tumor Response by MRI, As Assessed by Investigator Per Modified RECIST (in Participants Who Have PTEN-low Tumors)
Description	ORR was based on criteria related to changes in size of target lesions according to modified RECIST. Target lesions were selected on the basis of their size (lesions with the longest diameter) as well as the feasibility of reproducible repeated measurements. ORR was the sum of complete response (CR) and partial response (PR). CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Time Frame	Screening up to disease progression or death (assessed at screening, pre-surgical visit [approximately Weeks 10-12], early termination visit [up to Week 16])

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants who have PTEN-low tumors.

Arm/Group Title	Ipatasertib + Paclitaxel	Placebo + Paclitaxel
Arm/Group Description	Participants received ipatasertib orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel intravenous (IV) infusion every week (QW) for 3 cycles (12 total doses).	Participants received placebo (matching to ipatasertib) orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel IV infusion QW for 3 cycles (12 total doses).
Measure Participants	19	16
Number (95% Confidence Interval) [percentage of participants]	73.7 97%	50.0 66.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ipatasertib + Paclitaxel, Placebo + Paclitaxel
	Comments	Unstratified Analysis
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1486
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	23.68
	Confidence Interval	(2-Sided) 95%; -13.57 to 60.94
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% CI for difference in rates were constructed using normal approximation (Wald) with continuity correction.

7. Secondary Outcome

Title	Percentage of Participants With pCR in Breast and Axilla as Defined by ypT0/Tis ypN0 in the American Joint Committee on Cancer Staging System (in Participants Who Are Akt Diagnostic Positive [Dx+])
Description	pCR was defined by ypT0/Tis ypN0 in the AJCC Staging System with the following determination for breast and axilla by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue and N0: no cancer found in the lymph nodes.
Time Frame	Surgery visit (at approximately Weeks 14 to 19)

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants who are Akt Dx+.

Arm/Group Title	Ipatasertib + Paclitaxel	Placebo + Paclitaxel
Arm/Group Description	Participants received ipatasertib orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel intravenous (IV) infusion every week (QW) for 3 cycles (12 total doses).	Participants received placebo (matching to ipatasertib) orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel IV infusion QW for 3 cycles (12 total doses).
Measure Participants	28	34
Number (95% Confidence Interval) [percentage of participants]	17.9 23.6%	11.8 15.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ipatasertib + Paclitaxel, Placebo + Paclitaxel
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4980
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	6.09
	Confidence Interval	(2-Sided) 95%; -15.01 to 27.20
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% CI for difference in rates were constructed using normal approximation (Wald) with continuity correction method.

8. Secondary Outcome

Title	Percentage of Participants With pCR in Breast as Defined by ypT0/Tis in the American Joint Committee on Cancer Staging System (in Participants Who Are Akt Dx+)
Description	pCR was defined by ypT0/Tis in the AJCC Staging System with the following determination for breast by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue.
Time Frame	Surgery visit (at approximately Weeks 14 to 19)

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants who are Akt Dx+.

Arm/Group Title	Ipatasertib + Paclitaxel	Placebo + Paclitaxel
Arm/Group Description	Participants received ipatasertib orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel intravenous (IV) infusion every week (QW) for 3 cycles (12 total doses).	Participants received placebo (matching to ipatasertib) orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel IV infusion QW for 3 cycles (12 total doses).
Measure Participants	28	34
Number (95% Confidence Interval) [percentage of participants]	21.4 28.2%	11.8 15.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ipatasertib + Paclitaxel, Placebo + Paclitaxel
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3032
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	9.66
	Confidence Interval	() 95%; -12.25 to 31.58
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% CI for difference in rates were constructed using normal approximation (Wald) with continuity correction method.

9. Secondary Outcome

Title	Percentage of Participants With pCR According to American Joint Committee on Cancer Staging System, by Breast Cancer Subtype
Description	pCR was defined by ypT0/Tis in the AJCC Staging System with the following determination for breast subtypes by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue. The intrinsic molecular subtypes of breast cancer included here are luminal A (LumA), Her-2, basal-like, normal and unknown.
Time Frame	Surgery visit (at approximately Weeks 14 to 19)

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants.

Arm/Group Title	Ipatasertib + Paclitaxel	Placebo + Paclitaxel
Arm/Group Description	Participants received ipatasertib orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel intravenous (IV) infusion every week (QW) for 3 cycles (12 total doses).	Participants received placebo (matching to ipatasertib) orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel IV infusion QW for 3 cycles (12 total doses).
Measure Participants	76	75
Unknown	18.5 24.3%	21.9 29.2%
Basal	22.0 28.9%	10.8 14.4%
Her2	33.3 43.8%	0 0%
LumA	0 0%
Normal	50.0 65.8%	0 0%

10. Secondary Outcome

Title	Percentage of Participants With Response to Undergoing Breast Conserving Surgery (BCS) Among Participants With T2 or T3 Tumors
Description	After neoadjuvant treatment, the number of patients who is appropriate for breast conserving surgery is reported as a measure of efficacy of the treatment to shrink the tumor enough for patients to benefit from less aggressive surgical management. Breast-conserving surgery was defined as removal of part of the breast tissue during surgery. T2 or T3 in the AJCC Staging System were defined as follows: T2: tumor was more than 2 centimeter (cm) but no more than 5 cm across; T3: tumor was larger than 5 cm across.
Time Frame	Surgery visit (at approximately Weeks 14 to 19)

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants with T2 or T3 Tumors.

Arm/Group Title	Ipatasertib + Paclitaxel	Placebo + Paclitaxel
Arm/Group Description	Participants received ipatasertib orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel intravenous (IV) infusion every week (QW) for 3 cycles (12 total doses).	Participants received placebo (matching to ipatasertib) orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel IV infusion QW for 3 cycles (12 total doses).
Measure Participants	62	63
Number (95% Confidence Interval) [percentage of participants]	64.5 84.9%	60.3 80.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ipatasertib + Paclitaxel, Placebo + Paclitaxel
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6280
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	4.20
	Confidence Interval	(2-Sided) 95%; -14.37 to 22.76
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% CI for difference in rates were constructed using normal approximation (Wald) with continuity correction method.

11. Secondary Outcome

Title	Percentage of Participants With Response to Conversion to BCS Among Participants With T2 or T3 Tumors
Description	After neoadjuvant treatment, the number of patients who is appropriate for breast conserving surgery is reported as a measure of efficacy of the treatment to shrink the tumor enough for patients to benefit from less aggressive surgical management. Breast-conserving surgery was defined as removal of part of the breast tissue during surgery. T2 or T3 in the AJCC Staging System were defined as follows: T2: tumor was more than 2 centimeter (cm) but no more than 5 cm across; T3: tumor was larger than 5 cm across.
Time Frame	From screening to surgery visit (at approximately Weeks 14 to 19)

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants with T2 or T3 Tumors with response to conversion to BCS.

Arm/Group Title	Ipatasertib + Paclitaxel	Placebo + Paclitaxel
Arm/Group Description	Participants received ipatasertib orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel intravenous (IV) infusion every week (QW) for 3 cycles (12 total doses).	Participants received placebo (matching to ipatasertib) orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel IV infusion QW for 3 cycles (12 total doses).
Measure Participants	12	16
Number (95% Confidence Interval) [percentage of participants]	33.3 43.8%	25 33.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ipatasertib + Paclitaxel, Placebo + Paclitaxel
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6291
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	8.33
	Confidence Interval	(2-Sided) 95%; -33.04 to 49.71
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% CI for difference in rates were constructed using normal approximation (Wald) with continuity correction method.

12. Secondary Outcome

Title	Percentage of Participants With Adverse Events
Description	An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Time Frame	Screening up to Week 24

Outcome Measure Data

Analysis Population Description

The safety population was identical to the ITT population and included all randomized participants.

Arm/Group Title	Ipatasertib + Paclitaxel	Placebo + Paclitaxel
Arm/Group Description	Participants received ipatasertib orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel intravenous (IV) infusion every week (QW) for 3 cycles (12 total doses).	Participants received placebo (matching to ipatasertib) orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel IV infusion QW for 3 cycles (12 total doses).
Measure Participants	76	75
Number [percentage of participants]	100 131.6%	98.7 131.6%

13. Secondary Outcome

Title	Plasma Concentrations of Ipatasertib on Day 1 and Day 8
Description	Plasma samples for pharmacokinetic characterization was collected at various timepoints in all participants.
Time Frame	0.5 and 4 hours post dose on Day 1 of Cycle 1, 166 and 170 hours post dose from Day 1 of Cycle 1 (Cycle length = 28 days)

Outcome Measure Data

Analysis Population Description

The ITT population included all randomized participants. Reported here are data for participants with data available.

Arm/Group Title	Ipatasertib + Paclitaxel
Arm/Group Description	Participants received ipatasertib orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel intravenous (IV) infusion every week (QW) for 3 cycles (12 total doses).
Measure Participants	73
0.5 hours	290 (312)
4 hours	196 (93.0)
166 hours	37.5 (28.3)
170 hours	355 (204)

14. Secondary Outcome

Title	Minimum Observed Plasma Concentration (Cmin) of Ipatasertib
Description	Plasma samples for pharmacokinetic characterization was collected on Day 1 and Day 8 in all participants.
Time Frame	0.5 and 4 hours post dose on Day 1 of Cycle 1, 166 and 170 hours post dose from Day 1 of Cycle 1 (Cycle length = 28 days)

Outcome Measure Data

Analysis Population Description

The ITT population included all participants.

Arm/Group Title	Ipatasertib + Paclitaxel
Arm/Group Description	Participants received ipatasertib orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel intravenous (IV) infusion every week (QW) for 3 cycles (12 total doses).
Measure Participants	76
Mean (Standard Deviation) [ng/mL]	37.5 (28.3)

Adverse Events

Time Frame	2 years and 6 months
Adverse Event Reporting Description	The safety population was identical to the ITT population. The ITT population comprised all 151 randomized patients.
Arm/Group Title	Ipatasertib + Paclitaxel		Placebo + Paclitaxel
Arm/Group Description	Participants received ipatasertib orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel intravenous (IV) infusion every week (QW) for 3 cycles (12 total doses).		Participants received placebo (matching to ipatasertib) orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel IV infusion QW for 3 cycles (12 total doses).
All Cause Mortality
	Ipatasertib + Paclitaxel		Placebo + Paclitaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/76 (1.3%)		0/75 (0%)
Serious Adverse Events
	Ipatasertib + Paclitaxel		Placebo + Paclitaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/76 (13.2%)		3/75 (4%)
Blood and lymphatic system disorders
Sickle cell anaemia with crisis	1/76 (1.3%)		0/75 (0%)
Gastrointestinal disorders
Diarrhoea	1/76 (1.3%)		0/75 (0%)
General disorders
Pyrexia	1/76 (1.3%)		1/75 (1.3%)
Chest pain	1/76 (1.3%)		0/75 (0%)
Complication associated with device	1/76 (1.3%)		0/75 (0%)
General physical health deterioration	0/76 (0%)		1/75 (1.3%)
Infections and infestations
Device related infection	2/76 (2.6%)		0/75 (0%)
Pneumonia	1/76 (1.3%)		1/75 (1.3%)
Atypical pneumonia	1/76 (1.3%)		0/75 (0%)
Metabolism and nutrition disorders
Dehydration	1/76 (1.3%)		0/75 (0%)
Respiratory, thoracic and mediastinal disorders
Pneumonitis	1/76 (1.3%)		0/75 (0%)
Other (Not Including Serious) Adverse Events
	Ipatasertib + Paclitaxel		Placebo + Paclitaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	76/76 (100%)		73/75 (97.3%)
Blood and lymphatic system disorders
Anaemia	14/76 (18.4%)		11/75 (14.7%)
Neutropenia	7/76 (9.2%)		6/75 (8%)
Eye disorders
Dry eye	3/76 (3.9%)		4/75 (5.3%)
Lacrimation increased	4/76 (5.3%)		1/75 (1.3%)
Gastrointestinal disorders
Abdominal distension	4/76 (5.3%)		1/75 (1.3%)
Abdominal Pain	14/76 (18.4%)		6/75 (8%)
Abdominal pain upper	7/76 (9.2%)		4/75 (5.3%)
Constipation	10/76 (13.2%)		16/75 (21.3%)
Diarrhoea	66/76 (86.8%)		24/75 (32%)
Dry mouth	7/76 (9.2%)		6/75 (8%)
Gastrooesophageal reflux disease	5/76 (6.6%)		8/75 (10.7%)
Dyspepsia	12/76 (15.8%)		9/75 (12%)
Nausea	36/76 (47.4%)		23/75 (30.7%)
Stomatitis	5/76 (6.6%)		6/75 (8%)
Vomiting	17/76 (22.4%)		4/75 (5.3%)
General disorders
Asthenia	32/76 (42.1%)		29/75 (38.7%)
Fatigue	23/76 (30.3%)		24/75 (32%)
Mucosal dryness	4/76 (5.3%)		0/75 (0%)
Mucosal inflammation	14/76 (18.4%)		5/75 (6.7%)
Oedema peripheral	3/76 (3.9%)		5/75 (6.7%)
Pyrexia	8/76 (10.5%)		4/75 (5.3%)
Infections and infestations
Conjunctivitis	2/76 (2.6%)		5/75 (6.7%)
Folliculitis	5/76 (6.6%)		3/75 (4%)
Upper respiratory tract infection	3/76 (3.9%)		5/75 (6.7%)
Urinary tract infection	8/76 (10.5%)		9/75 (12%)
Viral upper respiratory tract infection	4/76 (5.3%)		7/75 (9.3%)
Injury, poisoning and procedural complications
Infusion related reaction	5/76 (6.6%)		4/75 (5.3%)
Investigations
Alanine aminotransferase increased	5/76 (6.6%)		5/75 (6.7%)
Aspartate aminotransferase increased	3/76 (3.9%)		4/75 (5.3%)
Neutrophil count decreased	4/76 (5.3%)		4/75 (5.3%)
Metabolism and nutrition disorders
Decreased appetite	11/76 (14.5%)		6/75 (8%)
Hyperglycaemia	3/76 (3.9%)		5/75 (6.7%)
Hypokalaemia	4/76 (5.3%)		2/75 (2.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	8/76 (10.5%)		6/75 (8%)
Musculoskeletal pain	5/76 (6.6%)		3/75 (4%)
Myalgia	6/76 (7.9%)		12/75 (16%)
Pain in extremity	4/76 (5.3%)		7/75 (9.3%)
Nervous system disorders
Dizziness	7/76 (9.2%)		8/75 (10.7%)
Dysgeusia	18/76 (23.7%)		17/75 (22.7%)
Hypoaesthesia	1/76 (1.3%)		4/75 (5.3%)
Neuropathy peripheral	14/76 (18.4%)		14/75 (18.7%)
Neurotoxicity	9/76 (11.8%)		6/75 (8%)
Paraesthesia	12/76 (15.8%)		9/75 (12%)
Peripheral sensory neuropathy	8/76 (10.5%)		13/75 (17.3%)
Headache	14/76 (18.4%)		15/75 (20%)
Psychiatric disorders
Anxiety	3/76 (3.9%)		6/75 (8%)
Insomnia	15/76 (19.7%)		15/75 (20%)
Renal and urinary disorders
Dysuria	1/76 (1.3%)		5/75 (6.7%)
Reproductive system and breast disorders
Amenorrhoea	1/76 (1.3%)		5/75 (6.7%)
Breast pain	4/76 (5.3%)		2/75 (2.7%)
Respiratory, thoracic and mediastinal disorders
Cough	10/76 (13.2%)		8/75 (10.7%)
Epistaxis	12/76 (15.8%)		9/75 (12%)
Skin and subcutaneous tissue disorders
Alopecia	40/76 (52.6%)		40/75 (53.3%)
Dermatitis Acneiform	4/76 (5.3%)		3/75 (4%)
Dry skin	5/76 (6.6%)		3/75 (4%)
Erythema	5/76 (6.6%)		4/75 (5.3%)
Onycholysis	5/76 (6.6%)		2/75 (2.7%)
Pruritus	6/76 (7.9%)		10/75 (13.3%)
Rash	19/76 (25%)		14/75 (18.7%)
Rash maculo-papular	4/76 (5.3%)		7/75 (9.3%)
Vascular disorders
Flushing	7/76 (9.2%)		4/75 (5.3%)
Hot flush	6/76 (7.9%)		5/75 (6.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.