DPT02: A Phase 2 Study of T-DXd in Patients With Selected HER2 Expressing Tumors

Sponsor

AstraZeneca (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04482309

Collaborator

Daiichi Sankyo Co., Ltd. (Industry)

268

Enrollment

Locations

Arms

33.9

Anticipated Duration (Months)

3.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is an open-label, multi-center, multi-cohort, Phase 2 study to evaluate the efficacy and safety of trastuzumab deruxtecan (T-DXd) for the treatment of selected HER2-expressing tumors.

This study will enroll 7 tumor-specific cohorts: urothelial bladder cancer, biliary tract cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer, and rare tumors.

Study hypothesis: Trastuzumab deruxtecan will show meaningful clinical activity and a favorable risk benefit profile in selected HER2-expressing solid tumors.

Condition or Disease	Intervention/Treatment	Phase
Bladder Cancer, Biliary Tract Cancer, Cervical Cancer, Endometrial Cancer, Ovarian Cancer, Pancreatic Cancer, Rare Tumors	Drug: Trastuzumab deruxtecan	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

268 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

This study will consist of seven cohorts of urothelial bladder cancer, biliary tract cancer, cervical cancer, endometrial cancer, ovarian cancer, Pancreatic cancer, and rare tumors.This study will consist of seven cohorts of urothelial bladder cancer, biliary tract cancer, cervical cancer, endometrial cancer, ovarian cancer, Pancreatic cancer, and rare tumors.

Masking:

None (Open Label)

Masking Description:

This study is Open-Label Study.

Primary Purpose:

Treatment

Official Title:

A Phase 2, Multicenter, Open-label Study to Evaluate the Efficacy and Safety of Trastuzumab Deruxtecan (T-DXd, DS-8201a) for the Treatment of Selected HER2 Expressing Tumors (DESTINY-PanTumor02)

Actual Study Start Date :

Aug 18, 2020

Anticipated Primary Completion Date :

Jun 16, 2023

Anticipated Study Completion Date :

Jun 16, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1 Cohort 1: Biliary tract cancer	Drug: Trastuzumab deruxtecan Trastuzumab deruxtecan by intravenous infusion Other Names: DS-8201a T-DXd
Experimental: Arm 2 Cohort 2: Bladder cancer	Drug: Trastuzumab deruxtecan Trastuzumab deruxtecan by intravenous infusion Other Names: DS-8201a T-DXd
Experimental: Arm 3 Cohort 3: Cervical cancer	Drug: Trastuzumab deruxtecan Trastuzumab deruxtecan by intravenous infusion Other Names: DS-8201a T-DXd
Experimental: Arm 4 Cohort 4: Endometrial cancer	Drug: Trastuzumab deruxtecan Trastuzumab deruxtecan by intravenous infusion Other Names: DS-8201a T-DXd
Experimental: Arm 5 Cohort 5: Ovarian cancer	Drug: Trastuzumab deruxtecan Trastuzumab deruxtecan by intravenous infusion Other Names: DS-8201a T-DXd
Experimental: Arm 6 Cohort 6: Pancreatic cancer	Drug: Trastuzumab deruxtecan Trastuzumab deruxtecan by intravenous infusion Other Names: DS-8201a T-DXd
Experimental: Arm 7 Cohort 7: Rare tumors	Drug: Trastuzumab deruxtecan Trastuzumab deruxtecan by intravenous infusion Other Names: DS-8201a T-DXd

Outcome Measures

Primary Outcome Measures

Objective Response Rate (ORR) [An average of approximately 12 months]
Confirmed ORR per RECIST 1.1 is the percentage of patients with Complete Response or Partial Response that is subsequently confirmed.

Secondary Outcome Measures

Duration of response (DoR) [An average of approximately 18 months]
DOR is defined as the time from the date of first documented response until the date of documented progression or death.
Disease control rate (DCR) [An average of approximately 18 months]
DCR is the percentage of subjects who have a best overall response of complete response (CR) or partial response (PR) or stable disease (SD).
Progression free survival (PFS) [An average of approximately 18 months]
PFS is the time from date of first dose of study treatment until the date of objective disease progression or death.
Proportion of patients alive and progression-free at 6 months and 12 months [Up to 12 months]
The proportion of patients alive and progression-free at 6 and 12 months (Kaplan-Meier estimates).
Overall survival (OS) [An average of approximately 30 months]
OS is the time from date of first dose of study treatment until death due to any cause.
Proportion of patients alive at 6 and 12 months [Up to 12 months]
The proportion of patients alive at 6 and 12 months (Kaplan-Meier estimates).
Occurrence of adverse events (AEs) and serious adverse events (SAEs) [An average of approximately 24 months]
Occurrence of AEs and SAEs graded according to NCI CTCAE v5.0.
Pharmacokinetics (PK) assessed by serum concentration of T-DXd, total anti-HER2 antibody and MAAA-1181 [An average of approximately 24 months]
Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for T-DXd, total anti-HER2 antibody and MAAA-1181a
The immunogenicity of T-DXd assessed by the presence of ADAs for T-DXd [An average of approximately 24 months]
Individual participant data and descriptive statistics will be provided for data at each time point.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Locally advanced, unresectable, or metastatic disease based on most recent imaging.
The respective cohorts for patient inclusion are:
Cohort 1: Biliary tract cancer
Cohort 2: Bladder cancer
Cohort 3: Cervical cancer
Cohort 4: Endometrial cancer
Cohort 5: Epithelial ovarian cancer
Cohort 6: Pancreatic cancer
Cohort 7: Rare tumors: This cohort will consist of patients with tumors that express HER2, excluding the tumors mentioned above, and breast, non-small cell lung cancer, gastric cancer, and colorectal cancer.
Progressed following prior treatment or who have no satisfactory alternative treatment option.
Prior HER2 targeting therapy is permitted.
HER2 expression for eligibility may be based on local or central assessment.
Has measurable target disease assessed by the Investigator based on RECIST version 1.1.
Has protocol- defined adequate organ function including cardiac, renal and hepatic function.

Exclusion Criteria:

History of non-infectious pneumonitis/ILD that required steroids, current ILD, or where suspected ILD that cannot be ruled out by imaging at screening
Lung-specific intercurrent clinically significant severe illnesses
Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals
Pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART
Known Somatic DNA mutation of HER2 (ERBB2) without tumoral HER2 protein expression.
Primary diagnosis of adenocarcinoma of the breast, adenocarcinoma of the colon or rectum, adenocarcinoma of the gastric body or gastro-esophageal junction, or non-small cell lung cancer.
Medical conditions that may interfere with the subject's participation in the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Duarte	California	United States	91010
2	Research Site	Santa Rosa	California	United States	95403
3	Research Site	Chicago	Illinois	United States	60637
4	Research Site	Muncie	Indiana	United States	47303
5	Research Site	Boston	Massachusetts	United States	02215
6	Research Site	Middletown	New Jersey	United States	07748
7	Research Site	Commack	New York	United States	11725
8	Research Site	Harrison	New York	United States	10604
9	Research Site	New York	New York	United States	10029
10	Research Site	Durham	North Carolina	United States	27710
11	Research Site	Houston	Texas	United States	77030
12	Research Site	Seattle	Washington	United States	98109
13	Research Site	Auchenflower		Australia	4066
14	Research Site	Camperdown		Australia	2050
15	Research Site	Heidelberg		Australia	3084
16	Research Site	Nedlands		Australia	6009
17	Research Site	Brussels		Belgium	1090
18	Research Site	Leuven		Belgium	3000
19	Research Site	Liège		Belgium	4000
20	Research Site	Montreal		Canada	H3T 1E2
21	Research Site	Quebec		Canada	G1J 1Z4
22	Research Site	Brno		Czechia	656 53
23	Research Site	Hradec Kralove		Czechia	500 05
24	Research Site	Olomouc		Czechia	775 20
25	Research Site	Praha 5		Czechia	150 06
26	Research Site	Praha 8		Czechia	180 81
27	Research Site	Gurgaon		India	122001
28	Research Site	Kolkata		India	700160
29	Research Site	Mumbai		India	400012
30	Research Site	Rohini		India	110 085
31	Research Site	Milan		Italy	20141
32	Research Site	Milan		Italy	20162
33	Research Site	Rome		Italy	168
34	Research Site	Seoul		Korea, Republic of	03080
35	Research Site	Seoul		Korea, Republic of	03722
36	Research Site	Seoul		Korea, Republic of	5505
37	Research Site	Seoul		Korea, Republic of	6351
38	Research Site	Amsterdam		Netherlands	1066CX
39	Research Site	Delft		Netherlands	2625 AD
40	Research Site	Groningen		Netherlands	9700
41	Research Site	Bydgoszcz		Poland	85-796
42	Research Site	Gdańsk		Poland	80-214
43	Research Site	Kraków		Poland	30-688
44	Research Site	Poznan		Poland	60-780
45	Research Site	Warszawa		Poland	02-781
46	Research Site	Kaluga		Russian Federation	248007
47	Research Site	Moscow		Russian Federation	115478
48	Research Site	Moscow		Russian Federation	117997
49	Research Site	Moscow		Russian Federation	121205
50	Research Site	Moscow		Russian Federation	143423
51	Research Site	Moscow		Russian Federation	143442
52	Research Site	Saint Petersburg		Russian Federation	195271
53	Research Site	Saint-Petersburg		Russian Federation	197758
54	Research Site	Barcelona		Spain	8035
55	Research Site	Córdoba		Spain	14004
56	Research Site	Madrid		Spain	28027
57	Research Site	Madrid		Spain	28040
58	Research Site	Madrid		Spain	28041
59	Research Site	Madrid		Spain	28046
60	Research Site	Valencia		Spain	46014
61	Research Site	Taichung		Taiwan	40705
62	Research Site	Tainan		Taiwan	736
63	Research Site	Taipei		Taiwan	100
64	Research Site	Taipei		Taiwan	11217
65	Research Site	Tao-Yuan		Taiwan	333
66	Research Site	Bangkok		Thailand	10210
67	Research Site	Bangkok		Thailand	10330
68	Research Site	Bangkok		Thailand	10400
69	Research Site	Chiang Mai		Thailand	50200
70	Research Site	Hat Yai		Thailand	90110
71	Research Site	Khon Kaen		Thailand	40002
72	Research Site	Muang		Thailand	50200
73	Research Site	Ongkharak		Thailand	26120
74	Research Site	London		United Kingdom	SW2 6JJ
75	Research Site	Manchester		United Kingdom	M20 4BX
76	Research Site	Sutton		United Kingdom	SM2 5PT