Clinical trial NCT04639219: A Study of T-DXd for the Treatment of Solid Tumors Harboring HER2 Activating Mutations
Official title: A Phase II, Multicenter, Open-label Study to Evaluate the Efficacy and Safety of Trastuzumab Deruxtecan (T-DXd) for the Treatment of Unresectable and/or Metastatic Solid Tumors Harboring HER2 Activating Mutations Regardless of Tumor Histology
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Advanced Solid Tumors With HER2 Mutation,eg:Colorectal,Urothelial,Gastric, Hepatobiliary,Endometrial,Melanoma,Ovarian,Cervical,Salivary Gland,Pancreatic,Breast
Keywords: HER2
T-DXd
DS-8201a
Trastuzumab Deruxtecan
Metastatic
Solid Tumors
Histology Agnostic
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Daiichi Sankyo Co., Ltd.
First posted: 2020-11-20
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open-label, multi-center, single arm, Phase II study to evaluate the efficacy and safety of T-DXd for the treatment of unresectable and/or metastatic solid tumors harboring specific HER2 activating mutations regardless of tumor histology. The target population are patients who have progressed following prior treatment or who have no satisfactory alternative treatment options, including approved second line therapies in the specific tumor type. Pre-specified HER2 mutations will be locally assessed using NGS tests or alternative methods. Prior HER2 targeting therapy is permitted.


Eligibility criteria: Inclusion Criteria:

* Adults ≥18 years old. Other age restrictions may apply as per local regulations.
* Unresectable and/or metastatic solid tumors with pre-specified HER2 mutations (S310F, S310Y, G660D, R678Q, D769Y, D769H, V777L, Y772_A775dup / A775_G776insYVMA, L755S, G778_P780dup / P780_Y781insGSP, T862A, and V842I locally determined by NGS or a validated nucleic acid-based methodology (eg, qPCR, digital PCR) on tumor tissue, who have progressed following prior treatment or who have no satisfactory alternative treatment options.
* Prior HER2 targeted therapy is permitted.
* All patients must provide an FFPE tumor sample for retrospective central HER2 testing.
* LVEF ≥50%
* ECOG 0-1
* All patients have measurable target disease assessed by the Investigator based on RECIST v1.1

Exclusion Criteria:

* HER2 overexpressing (IHC3+ or IHC2+/ISH+) breast, gastric or gastroesophageal junction adenocarcinoma.
* HER2 mutant NSCLC.
* Medical history of myocardial infarction within 6 months before randomization/enrolment, symptomatic CHF, unstable angina pectoris, clinically important cardiac arrhythmias, or a recent (\< 6 months) cardiovascular event including stroke.
* History of non-infectious pneumonitis/ILD, current ILD, or where suspected ILD cannot be ruled out by imaging at screening
* Corrected QT interval by Fridericia's formula (QTcF) prolongation to \> 470 msec (females) or \> 450 msec (males) based on average of the screening triplicate 12-lead ECG.
* Lung-specific intercurrent clinically significant severe illnesses.
* History of active primary immunodeficiency, known HIV, active HBV or HCV infection
* 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).
* Has spinal cord compression or clinically active central nervous system metastases.

Primary outcomes:
measure: Confirmed Overall Response Rate (ORR) as Per RECIST v1.1 Using Independent Central Review (ICR)
timeFrame: Tumor scans performed at screening,then every 6 weeks (q6w) +/- 1 week relative to date of first treatment administration until RECIST v1.1 objective PD, withdrawal of consent, or death by any cause, up to DCO date of 25 Jan 2023 (approximately 24 months)
Secondary outcomes:
measure: Duration of Response (DoR) as Per RECIST v1.1 Using ICR and Investigator Assessment
timeFrame: Tumor scans performed at screening, then q6w +/- 1 week relative to the date of first treatment administration until RECIST v1.1 objective PD, withdrawal of consent, or death by any cause, up to DCO date of 25 Jan 2023 (approximately 24 months)
measure: Disease Control Rate (DCR) as Per RECIST v1.1 Using ICR and Investigator Assessment
timeFrame: Tumor scans performed at screening, then q6w +/- 1 week relative to the date of first treatment administration until RECIST v1.1 objective PD, withdrawal of consent, or death by any cause, up to DCO date of 25 Jan 2023 (approximately 24 months)
measure: PFS as Per RECIST v1.1 Using ICR and Investigator Assessment
timeFrame: Tumor scans performed at screening, then q6w +/- 1 week relative to the date of first treatment administration until RECIST v1.1 objective PD or death by any cause, up to DCO date of 25 Jan 2023 (approximately 24 months)
measure: Percentage of Participants Alive and Progression-Free at 6 and 12 Months as Per RECIST v1.1 Using ICR and Investigator Assessment
timeFrame: At Months 6 and 12
measure: Confirmed ORR as Per RECIST v1.1 Using Investigator Assessment
timeFrame: Tumor scans performed at screening, then q6w +/- 1 week relative to the date of first treatment administration until RECIST v1.1 objective PD, withdrawal of consent, or death by any cause, up to DCO date of 25 Jan 2023 (approximately 24 months)
measure: Overall Survival (OS)
timeFrame: From the date of first treatment administration up to death, approximately 24 months
measure: Percentage of Participants Alive at 6 and 12 Months
timeFrame: At Months 6 and 12
measure: Serum Concentrations of T-DXd and Total Anti-HER2 Antibody
timeFrame: Pre-infusion and 15 minutes post-infusion in Cycles 1, 2 and 4 and 5 hours post-infusion in Cycle 1 (each cycle 21 days)
measure: Serum Concentrations of Deruxtecan (MAAA-1181a)
timeFrame: Pre-infusion and 15 minutes post-infusion in Cycles 1, 2 and 4 and 5 hours post-infusion in Cycle 1 (each cycle 21 days)
measure: Percentage of Participants With Anti-Drug Antibodies (ADA) to T-DXd
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
city: Santa Rosa
country: United States
facility: Research Site
state: California
city: Muncie
country: United States
facility: Research Site
state: Indiana
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Middletown
country: United States
facility: Research Site
state: New Jersey
city: Commack
country: United States
facility: Research Site
state: New York
city: Harrison
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Houston
country: United States
facility: Research Site
state: Texas
city: Fairfax
country: United States
facility: Research Site
state: Virginia
city: Anderlecht
country: Belgium
facility: Research Site
city: Toronto
country: Canada
facility: Research Site
state: CA
city: Copenhagen
country: Denmark
facility: Research Site
city: Bordeaux
country: France
facility: Research Site
city: Lyon Cedex 08
country: France
facility: Research Site
city: Villejuif Cedex
country: France
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Milan
country: Italy
facility: Research Site
city: Napoli
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
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Pamplona
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
Study officials:
References: