Efficacy, tolerability, and biologic activity of a novel ... › uploads › media › STUDY...
6
Presented on: ASCO20 Virtual, 29.05. - 31.05.2020 Efficacy, tolerability, and biologic activity of a novel regimen of tremelimumab in combination with durvalumab for patients with advanced hepatocellular carcinoma R. Katie Kelley, 1 Bruno Sangro, 2 William Harris, 3 Masafumi Ikeda, 4 Takuji Okusaka, 5 Yoon-Koo Kang, 6 Shukui Qin, 7 David Wai Meng Tai, 8 Hoyeong Lim, 9 Thomas Yau, 10 Wei Peng Yong, 11 Ann-Lii Cheng, 12 Antonio Gasbarrini, 13 Silvia Damian, 14 Jordi Bruix, 15 Mitesh Borad, 16 Philip He, 17 Alejandra Negro, 17 Masatoshi Kudo 18 and Ghassan K. Abou-Alfa 19 1 University of California, San Francisco, CA; 2 Liver Unit, Clinica Universidad de Navarra, IDISNA and CIBEREHD, Pamplona, Spain; 3 University of Washington, Seattle, WA; 4 National Cancer Centre Hospital East, Kashiwa, Japan; 5 National Cancer Center Hospital, Tokyo, Japan; 6 Asan Medical Center, Department of Oncology, Seoul, South Korea; 7 PLA Cancer Center & Bayi Clinical Trial Institute, Nanjing, China; 8 National Cancer Centre Singapore; 9 Samsung Medical Center Seoul, South Korea; 10 Queen Mary Hospital, Hong Kong; 11 National University Cancer Institute, Singapore; 12 National Taiwan University, Taipei, Taiwan; 13 Catholic University of the Sacred Heart, Milano, Italy; 14 Fondazione IRCCS Instituto Nazionale Tumori, Milano, Italy; 15 BCLC, Hospital Clinic, IDIBAPS and CIBEREHD, Barcelona, Spain; 16 Mayo Clinic Cancer Center, Phoenix, AZ; 17 AstraZeneca, Gaithersburg, MD; 18 Kindai University Faculty of Medicine, Osaka, Japan; 19 Memorial Sloan Kettering Cancer Center, New York, NY and Weill Medical College at Cornell University New York, NY.
Transcript of Efficacy, tolerability, and biologic activity of a novel ... › uploads › media › STUDY...
Presented on: ASCO20 Virtual, 29.05. - 31.05.2020
Efficacy, tolerability, and biologic activity of a novel regimen of tremelimumab in combination with durvalumab for patients with advanced hepatocellular carcinoma
R. Katie Kelley,1 Bruno Sangro,2 William Harris, 3 Masafumi Ikeda,4 Takuji Okusaka,5 Yoon-Koo Kang,6 Shukui Qin,7 David Wai Meng Tai,8 Hoyeong Lim,9 Thomas Yau,10 Wei Peng Yong,11 Ann-Lii Cheng,12 Antonio Gasbarrini,13 Silvia Damian,14 Jordi Bruix,15 Mitesh Borad,16 Philip He,17 Alejandra Negro,17 Masatoshi Kudo18 and Ghassan K. Abou-Alfa19
1 University of California, San Francisco, CA; 2Liver Unit, Clinica Universidad de Navarra, IDISNA and CIBEREHD, Pamplona, Spain; 3University of Washington, Seattle, WA; 4National Cancer Centre Hospital East, Kashiwa, Japan; 5National Cancer Center Hospital, Tokyo, Japan; 6Asan Medical Center, Department of Oncology, Seoul, South Korea; 7PLA Cancer Center & Bayi Clinical Trial Institute, Nanjing, China; 8National Cancer Centre Singapore; 9Samsung Medical Center Seoul, South Korea; 10Queen Mary Hospital, Hong Kong; 11National University Cancer Institute, Singapore; 12National Taiwan University, Taipei, Taiwan; 13Catholic University of the Sacred Heart, Milano, Italy; 14 Fondazione IRCCS Instituto Nazionale Tumori, Milano, Italy; 15 BCLC, Hospital Clinic, IDIBAPS and CIBEREHD, Barcelona, Spain; 16Mayo Clinic Cancer Center, Phoenix, AZ; 17AstraZeneca, Gaithersburg, MD; 18Kindai University Faculty of Medicine, Osaka, Japan; 19Memorial Sloan Kettering Cancer Center, New York, NY and Weill Medical College at Cornell University New York, NY.
Presented on: ASCO20 Virtual, 29.05. - 31.05.2020
Study 22 Design
tremelimumab 300 mg x 1 dose + durvalumab 1500 mg Q4W durvalumab 1500 mg Q4W tremelimumab monotherapy 750 mg Q4W x 7 doses, Q12W thereafter Tremelimumab 75 mg x 4 doses + durvalumab 1500 mg Q4W
T300+D D T T75+D
Treatments and Regimens
Key Milestones FSI Part 2A February 2017 FSI Part 2B October 2017
Key Eligibility
• Unresectable HCC with fresh or archival tumor biopsy sample available
• Progressed on, intolerant to, or refused prior sorafenib
• Child Pugh A liver function
Objectives and Assessments
Primary Endpoint: Safety
Key Secondary Endpoints • Overall survival • Objective response rate • Duration of response
Key Assessments • Multiphase imaging Q8 weeks • Circulating immune cells • PD-L1 status (Ventana SP263)
Safety run-in Efficacy gating cohort1
T75+D (n = 40)
Key Milestones FSI Part 3 February 2018 LSI Part 3 April 2019
allocatedsafety run-in T300+D (n = 10)
PART 1 PART 2A PART 3
PART 2B
Safety run-in Efficacy gating cohort1 T75+D (n = 40)
RR
D (n = 40)
T (n = 36)
T75+D (n = 39)
T300+D (n = 65)
D (n = 64)
T (n = 33)
T75+D (n = 45)
1. Kelley RK, et al. JCO, 2017.35:4073-4073
Presented on: ASCO20 Virtual, 29.05. - 31.05.2020
Treatment-related Adverse Events (≥5% by Category)
n (%)
Patients with any TRAE
EndocrineHyperthyroidism
Hypothyroidism
Skin and subcutaneous tissue disordersPruritus
Rash
Rash maculo-papular
UrticariaMusculoskeletal and connective tissue disorders
Arthralgia
Myalgia
Myositis
General disorders and administration site conditionsFatigue
Investigations
Lipase increased
Amylase increased
T300+D (n = 74)
All grades Grade ≥3 All grades Grade ≥3 All grades Grade ≥3 All grades Grade ≥3
D (n = 101)
T (n = 69)
T75+D (n = 82)
61 (82.4)
6 (8.1)
6 (8.1)
24 (32.4)
24 (32.4)
2 (2.7)
2 (2.7)
0
2 (2.7)
0
8 (10.8)
11 (14.9)
9 (12.2)
27 (36.5)
0
0
0
2 (2.7)
1 (1.4)
0
0
0
0
0
5 (6.8)
5 (6.8)
61 (60.4)
2 (2.0)
10 (9.9)
11 (10.9)
7 (6.9)
2 (2.0)
0
2 (2.0)
1 (1.0)
1 (1.0)
9 (8.9)
2 (2.0)
1 (1.0)
21 (20.8)
0
0
0
0
0
0
0
0
1 (1.0)
1 (1.0)
1 (1.0)
0
58 (84.1)
0
2 (2.9)
19 (27.5)
15 (21.7)
7 (10.1)
2 (2.9)
3 (4.3)
1 (1.4)
0
11 (15.9)
3 (4.3)
9 (13.0)
30 (43.5)
0
0
1 (1.4)
2 (2.9)
0
0
0
1 (1.4)
0
0
0
4 (5.8)
57 (69.5)
4 (4.9)
7 (8.5)
13 (15.9)
11 (13.4)
5 (6.1)
1 (1.2)
2 (2.4)
1 (1.2)
0
8 (9.8)
6 (7.3)
4 (4.9)
20 (24.4)
1 (1.2)
0
0
0
0
0
0
0
0
0
1 (1.2)
4 (4.9)
Presented on: ASCO20 Virtual, 29.05. - 31.05.2020
Treatment-related Adverse Events (≥5% by Category), cont.
n (%)
Patients with any TRAE
Abdominal pain
Ascites
Colitis
Diarrhea
Hepatobiliary disordersHepatic failure
Portal vein thrombosis
Investigations (Hepatic)ALT increased
AST increasedBlood alkaline phosphatase increased
Blood bilirubin increased
GGT increased
T300+D (n = 74)
All grades Grade ≥3 All grades Grade ≥3 All grades Grade ≥3 All grades Grade ≥3
D (n = 101)
T (n = 69)
T75+D (n = 82)
61 (82.4)
2 (2.7)
1 (1.4)
0
3 (4.1)
7 (9.5)
0
0
1 (1.4)
11 (14.9)
12 (16.2)
6 (8.1)
4 (5.4)
2 (2.7)
27 (36.5)
0
0
0
2 (2.7)
1 (1.4)
0
0
1 (1.4)
3 (4.1)
9 (12.2)
3 (4.1)
1 (1.4)
2 (2.7)
61 (60.4)
0
0
0
0
9 (8.9)
1 (1.0)
1 (1.0)
0
5 (5.0)
8 (7.9)
7 (6.9)
3 (3.0)
2 (2.0)
21 (20.8)
0
0
0
0
1 (1.0)
1 (1.0
1 (1.0)
0
0
3 (3.0)
1 (1.0)
0
0
58 (84.1)
5 (7.2)
1 (1.4)
0
1 (1.4)
14 (20.3)
0
1 (1.4)
0
7 (10.1)
10 (14.5)
1 (1.4)
2 (2.9)
2 (2.9)
30 (43.5)
0
0
0
1 (1.4)
6 (8.7)
0
1 (1.4)
0
3 (4.3)
6 (8.7)
0
0
1 (1.4)
57 (69.5)
4 (4.9)
0
2 (2.4)
1 (1.2)
10 (12.2)
1 (1.2)
2 (2.4)
0
8 (9.8)
12 (14.6)
1 (1.2)
4 (4.9)
1 (1.2)
20 (24.4)
0
0
1 (1.2)
1 (1.2)
1 (1.2)
1 (1.2)
1 (1.2)
0
2 (2.4)
7 (8.5)
0
0
0
Gastrointestinal disorders
Immune-mediated pancreatitis
Hepatitis
ALT, Alanine aminotransferase; AST, Aspartate aminotransferase; GGT, Gamma-glutamyltransferase
Presented on: ASCO20 Virtual, 29.05. - 31.05.2020
Overall Survival
Longest median OS observed with T300+D
Presented on: ASCO20 Virtual, 29.05. - 31.05.2020
Conclusions
• All arms demonstrated an acceptable safety profile. - No new safety signals were identified beyond the established safety profile for each agent, alone or in combination.
• A single, priming dose of tremelimumab combined with monthly durvalumab (T300+D arm) showed promising clinical acitivity in a predominantly second-line HCC population.
- The confirmed ORR per RECIST v1.1 was 24% (median DOR, not reached) in the T300+D arm.
- Median OS (95% CI) was 18.73 (10.78-27.27) months in the T300+D arm.
• Across all arms, T300+D provides the best benefit-risk profile. - The unique association of the T300+D regimen with proliferative CD8+ T cells provides a biologic rationale for the observed
treatment response.
• T300+D and D are being evaluated vs sorafenib in the ongoing phase 3 HIMALAYA study (NCT03298451) in first-line HCC.
