1. Atezolizumab + Nab-Paclitaxel Well Tolerated and Active in Metastatic TNBC
CCO Independent Conference Coverage* of the 2016 ASCO Annual Meeting, June 3-7, 2016
*CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs.
TNBC, triple-negative breast cancer.
This activity is supported by educational grants from Amgen, Ariad, Bayer Healthcare Pharmaceuticals, Celgene Corporation, Genentech, Incyte, Merck, and Taiho Pharmaceuticals.

2. Atezolizumab + Nab-Paclitaxel in mTNBC
Pts with mTNBC are treated with chemotherapy, but prognosis remains poor
Atezolizumab: a humanized anti-PD-L1 monoclonal antibody
Blocks PD-L1 from binding to PD-1 and B7.1 to restore tumor-specific T-cell immunity
Approved in US for urothelial carcinoma; produced durable responses in mTNBC[1]
Nab-paclitaxel: solvent free, albumin-bound form of paclitaxel
Designed to increase antitumor activity and reduce AEs
Approved in US for MBC after failure of combination chemo for metastatic disease or relapse within 6 months of adjuvant chemotherapy
PD-L1 highly expressed in TNBC samples and in ~ half of all breast cancer[2,3]
PD-L1/PD-1 inhibitors combined with chemotherapy may be synergistic[4]
Phase Ib study evaluates combination of atezolizumab plus nab-paclitaxel in patients with mTNBC; interim results reported[5]
mTNBC, metastatic triple-negative breast cancer.
1. Emens LA, et al. AACR Abstract 2859.
2. Mittendorf EA, et al. Cancer Immunol Res. 2014;2:
3. Ghebeh H, et al. Neoplasia. 2006;8:
4. Liu SV, et al. ASCO Abstract 8030.
5. Adams S, et al. ASCO Abstract 1009.
Slide credit: clinicaloptions.com
References included in slide notes

3. Atezolizumab + Nab-Paclitaxel in mTNBC: Phase Ib Study Design
GP28328: a multicenter, multicohort phase Ib study; arm F includes pts with TNBC (metastatic or unresectable, locally advanced)[1,2]
Primary endpoint: safety and tolerability
Secondary endpoints: response per RECIST v1.1 (ORR, DoR, PFS) and immune- modified response criteria; pharmacokinetics, biomarker analyses
Atezolizumab + + + + + +
Nab-paclitaxel + + + + + + + + +
Pts with TNBC
≤ 2 previous
systemic cytotoxics
ECOG PS 0/1;
no CNS cancer or
untreated/active
CNS metastases;
available tumor
sample
Atezolizumab (800 mg) + nab-paclitaxel (125 mg/m2), as long as clinical benefit received;
Nab-paclitaxel for
at least 4 cycles, unless disease progression or unacceptable toxicity; if discontinued, atezolizumab as monotherapy
Safety Cohort (n = 8) B
Cycle 1, Day 1
Cycle 2, Day 1
Cycle 3, Day 1
Atezolizumab - + + + + +
Nab-paclitaxel + + + + + + + + +
B, biopsy; CNS, central nervous system; DoR, duration of response; ECOG, Eastern Cooperative Oncology Group; mTNBC, metastatic triple-negative breast cancer; PS, performance status; RECIST, Response Evaluation Criteria in Solid Tumors; TNBC, triple-negative breast cancer.
Serial Biopsy Cohort (n = 24) B B B
Cycle 1, Day 1
Cycle 2, Day 1
Cycle 3, Day 1
(weeks)
1. Adams S, et al. ASCO Abstract ClinicalTrials.gov: NCT
Slide credit: clinicaloptions.com

4. Atezolizumab + Nab-Paclitaxel in mTNBC: Patient Population
Characteristic
Pts (N = 32*)
Median age, yrs (range)
56 (32-84)
ECOG PS, n (%) 1
6 (19)
26 (81)
Metastatic sites, n (%)
Visceral
Nodal only
Other
15 (47)
2 (6)
Median number of previous systemic therapies, n (range)
5.0 (1-10)
Number of previous systemic therapies (including [neo]adjuvant therapy), n (%)†
1-2
3-4
≥ 5
13 (41)
17 (53)
Previous taxane use, n (%)
28 (88)
ECOG, Eastern Cooperative Oncology Group; mTNBC, metastatic triple-negative breast cancer.
*Safety evaluable population: ≥ 1 dose atezolizumab.
†Individual agents counted separately.
Slide credit: clinicaloptions.com
Adams S, et al. ASCO Abstract 1009.

5. Atezolizumab + Nab-Paclitaxel in mTNBC: Safety and Tolerability (Primary Endpoint)
Median safety follow-up: 6.1 mos (range: mos)
Median duration of exposure: 5.4 mos (range: 0-17 mos) for atezolizumab; 4.2 mos (range: 0-12 mos) for nab-paclitaxel
No reported deaths were related to study treatment
Treatment-Related AE (Grade 3/4 AEs Occurring in ≥ 1% of Pts), %
Pts (N = 32)
All Grades
Grade ≥ 3
All
100 69
Neutropenia/decreased neutrophil count 66 46
Thrombocytopenia and decreased platelet count 16 9
Diarrhea 41 6
Anemia 22
Decreased white blood cell count
AE, adverse event; mTNBC, metastatic triple-negative breast cancer.
Slide credit: clinicaloptions.com
Adams S, et al. ASCO Abstract 1009.

6. Atezolizumab + Nab-Paclitaxel in mTNBC: Safety and Tolerability (Primary Endpoint)
Atezolizumab-Related AE (Any Grade AE in ≥ 10% of Pts), %
Pts (N = 32)
All Grades
Grade ≥ 3
Fatigue 34 --
Neutropenia/decreased neutrophil count 28 9
Pyrexia 25
Diarrhea 19 3
Peripheral neuropathy/peripheral sensory neuropathy
Nausea 16
Alopecia 13
Headache
Pruritus
AE, adverse event; AST, aspartate aminotransferase; mTNBC, metastatic triple-negative breast cancer.
Additional atezolizumab-related grade 3/4 AEs: syncope, type 1 diabetes mellitus, anemia, thrombocytopenia/platelet count decreased (n = 3), febrile neutropenia, AST increased, white blood cells decreased, and pneumonia mycoplasmal (n = 1 except where indicated)
Slide credit: clinicaloptions.com
Adams S, et al. ASCO Abstract 1009.

7. Atezolizumab + Nab-Paclitaxel in mTNBC: Efficacy (Secondary Endpoints)
Among 12 responders, 6 (50%) remain on atezolizumab; 1 for > 17 mos
Median DoR not reached; PFS and OS data not yet mature
Responses observed in pts regardless of PD-L1 expression level; trend toward increase in baseline TILs for responding pts
Best Overall Response (RECIST v1.1)
First Line
(n = 13)
Second Line
(n = 9)
Third Line+
(n = 10)
All
(N = 32)
Confirmed ORR, % (95% CI)
46 (19-75)
22 (3-60)
40 (12-74)
38 (21-56)
CR, % 8 3
PR, % 38 22 40 34
SD, % 67 30 44
PD, % 15 16
Missing or not estimable, % 11
Median DoR, mos (range)
NE (2.9 to 11.5+)
NE (9.1 to 13.1+)
NE (1.9+ to 5.6+)
DoR, duration of response; mTNBC, metastatic triple-negative breast cancer; NE, not estimable; PD, progressive disease; RECIST, Response Evaluation Criteria in Solid Tumors; SD, stable disease; TILs, tumor infiltrating lymphocytes.
Slide credit: clinicaloptions.com
Adams S, et al. ASCO Abstract 1009.

8. Atezolizumab + Nab-Paclitaxel in mTNBC: Conclusions
Atezolizumab + nab-paclitaxel well tolerated and active in mTNBC[1]
Safety profile similar to that of single agents
Durable responses achieved across all lines of therapy
Clinical response seen regardless of PD-L1 expression
Ongoing phase III randomized trial evaluating this combination in previously untreated mTNBC[2]
mTNBC, metastatic triple-negative breast cancer.
1. Adams S, et al. ASCO Abstract ClinicalTrials.gov. NCT
Slide credit: clinicaloptions.com

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