Clinical trial NCT04482309: A Phase 2 Study of T-DXd in Patients With Selected HER2 Expressing Tumors
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Part 1: Bladder, Biliary Tract, Cervical, Endometrial, Ovarian, Pancreatic Cancer, Rare Tumors, Any Tumor Type Excluding Breast, Gastric, Colorectal Cancer
Part 2: HER2 Expressing/Amplified Solid Tumors Excluding Breast, Gastric, Colorectal Cancer
Keywords: T-DXd, DS-8201a, Trastuzumab Deruxtecan, HER2
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Daiichi Sankyo Co., Ltd.
First posted: 2020-07-22
Enrollment: 468
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study will consist of Part 1 which includes 7 cohorts of: urothelial bladder cancer, biliary tract cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer, and rare tumors; and Part 2 which includes 5 cohorts A to E of: A) any tumor type that is HER2 IHC 3+ (excluding breast, gastric cancer, and colorectal cancer), B) any tumor type that is HER2 IHC 2+/ISH+ (excluding breast, gastric cancer, and colorectal cancer), C) HER2 IHC 2+ or 1+ endometrial cancer, D) HER2 IHC 2+ or 1+ ovarian cancer, and E) HER2 IHC 2+ or 1+ cervical cancer.
Primary purpose: TREATMENT

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 consist of Part 1 which includes 7 cohorts of: urothelial bladder cancer, biliary tract cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer, and rare tumors; and Part 2 which includes 5 cohorts A to E of: A) any tumor type that is HER2 IHC 3+ (excluding breast, gastric cancer, and colorectal cancer), B) any tumor type that is HER2 IHC 2+/ISH+ (excluding breast, gastric cancer, and colorectal cancer), C) HER2 IHC 2+ or 1+ endometrial cancer, D) HER2 IHC 2+ or 1+ ovarian cancer, and E) HER2 IHC 2+ or 1+ cervical cancer.

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


Eligibility criteria: Inclusion Criteria:

* Locally advanced, unresectable, or metastatic disease based on most recent imaging.
* Part 1: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.
* Part 2:The respective cohorts for patient inclusion are:

  * Cohort A: Metastatic or advanced solid tumors that are HER2 IHC 3+ (excluding breast, gastric cancer, and colorectal cancer). Patients with non-small cell lung cancer can be included.
  * Cohort B: Metastatic or advanced solid tumors that are HER2 IHC 2+/ISH+ any tumor type (excluding breast, gastric cancer, and colorectal cancer). Patients with non-small cell lung cancer can be included.
  * Cohort C: Metastatic or advanced solid endometrial cancer that is HER2 IHC 2+ or 1+.
  * Cohort D: Metastatic or advanced ovarian cancer that is HER2 IHC 2+ or 1+.
  * Cohort E: Metastatic or advanced solid cervical cancer that is HER2 IHC 2+ or 1+.
* Progressed following prior treatment or who have no satisfactory alternative treatment option.
* Prior HER2 targeting therapy is permitted.
* HER2 expression scored using current ASCO/CAP guidelines for scoring HER2 for gastric cancer.

  * Part 1: IHC 3+ or IHC 2+ by local or central assessment
  * Part 2: IHC and ISH results by central assessment as pre-defined for each cohort
* 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 for Part 1. For Part 2, patients with primary diagnosis of adenocarcinoma of the breast, adenocarcinoma of the colon or rectum, adenocarcinoma of the gastric body or gastro-esophageal junction will be excluded.
* Medical conditions that may interfere with the subject's participation in the study.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: An average of approximately 6 months
Secondary outcomes:
measure: Duration of response (DoR)
timeFrame: An average of approximately 6 months
measure: Disease control rate (DCR)
timeFrame: An average of approximately 6 months
measure: Progression free survival (PFS)
timeFrame: An average of approximately 6 months
measure: Proportion of patients alive and progression-free at 6 months and 12 months
timeFrame: Up to 12 months
measure: Overall survival (OS)
timeFrame: An average of approximately 14 months
measure: Proportion of patients alive at 6 and 12 months
timeFrame: Up to 12 months
measure: Occurrence of adverse events (AEs) and serious adverse events (SAEs)
timeFrame: An average of approximately 8 months
measure: Pharmacokinetics (PK) assessed by serum concentration of T-DXd, total anti-HER2 antibody and MAAA-1181
timeFrame: An average of approximately 8 months
measure: The immunogenicity of T-DXd assessed by the presence of ADAs for T-DXd
timeFrame: An average of approximately 6 months
Other outcomes:
Locations:
city: Burbank
country: United States
facility: Research Site
state: California
city: Duarte
country: United States
facility: Research Site
state: California
city: Fullerton
country: United States
facility: Research Site
state: California
city: La Jolla
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Santa Rosa
country: United States
facility: Research Site
state: California
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Muncie
country: United States
facility: Research Site
state: Indiana
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Detroit
country: United States
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state: Michigan
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Middletown
country: United States
facility: Research Site
state: New Jersey
city: Harrison
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Rochester
country: United States
facility: Research Site
state: New York
city: Durham
country: United States
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state: North Carolina
city: Columbus
country: United States
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state: Ohio
city: Nashville
country: United States
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state: Tennessee
city: Houston
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state: Texas
city: Fairfax
country: United States
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state: Virginia
city: Seattle
country: United States
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state: Washington
city: Auchenflower
country: Australia
facility: Research Site
city: Blacktown
country: Australia
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city: Camperdown
country: Australia
facility: Research Site
city: Heidelberg
country: Australia
facility: Research Site
city: Melbourne
country: Australia
facility: Research Site
city: Nedlands
country: Australia
facility: Research Site
city: Brussels
country: Belgium
facility: Research Site
city: Bruxelles
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Liège
country: Belgium
facility: Research Site
city: Barretos
country: Brazil
facility: Research Site
city: Curitiba
country: Brazil
facility: Research Site
city: Natal
country: Brazil
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city: Porto Alegre
country: Brazil
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city: Porto Alegre
country: Brazil
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city: Porto Alegre
country: Brazil
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city: Ribeirão Preto
country: Brazil
facility: Research Site
city: São Paulo
country: Brazil
facility: Research Site
city: Vitória
country: Brazil
facility: Research Site
city: Kelowna
country: Canada
facility: Research Site
state: British Columbia
city: Hamilton
country: Canada
facility: Research Site
state: Ontario
city: London
country: Canada
facility: Research Site
state: Ontario
city: Ottawa
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Montreal
country: Canada
facility: Research Site
city: Quebec
country: Canada
facility: Research Site
city: Brno
country: Czechia
facility: Research Site
city: Hradec Kralove
country: Czechia
facility: Research Site
city: Olomouc
country: Czechia
facility: Research Site
city: Ostrava
country: Czechia
facility: Research Site
city: Praha 5
country: Czechia
facility: Research Site
city: Praha 8
country: Czechia
facility: Research Site
city: Delhi
country: India
facility: Research Site
city: Gurgaon
country: India
facility: Research Site
city: Kolkata
country: India
facility: Research Site
city: Madurai
country: India
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city: Mumbai
country: India
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city: Mumbai
country: India
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city: Nashik
country: India
facility: Research Site
city: Milan
country: Italy
facility: Research Site
city: Milan
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Rome
country: Italy
facility: Research Site
city: Chuo-ku
country: Japan
facility: Research Site
city: Kashiwa
country: Japan
facility: Research Site
city: Suita-shi
country: Japan
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Delft
country: Netherlands
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city: Groningen
country: Netherlands
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Gdańsk
country: Poland
facility: Research Site
city: Gliwice
country: Poland
facility: Research Site
city: Kraków
country: Poland
facility: Research Site
city: Poznan
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Kaluga
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Córdoba
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Tainan
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Tao-Yuan
country: Taiwan
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Chiang Mai
country: Thailand
facility: Research Site
city: Hat Yai
country: Thailand
facility: Research Site
city: Khon Kaen
country: Thailand
facility: Research Site
city: Muang
country: Thailand
facility: Research Site
city: Muang
country: Thailand
facility: Research Site
city: Ongkharak
country: Thailand
facility: Research Site
city: Sisaket
country: Thailand
facility: Research Site
city: Glasgow
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Northwood Middlesex
country: United Kingdom
facility: Research Site
city: Sutton
country: United Kingdom
facility: Research Site
Study officials:
References: