A Phase Ib Multicenter, Open-label Dose-escalation Study to Evaluate the Safety and Tolerability of Trastuzumab Deruxtecan (T-DXd) and Durvalumab in Combination with Cisplatin, Carboplatin or Pemetrexed in First-line Treatment of Patients with Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) and Human Epidermal Growth Factor Receptor 2 Overexpression (HER2+) (DESTINY-Lung03) (D967YC00001)
- Conditions
- lungcancerMetatstatic Non Small Cell Lung Cancer10038666
- Registration Number
- NL-OMON50973
- Lead Sponsor
- Astra Zeneca
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 4
- Histologically documented stage III locally advanced/metastatic and
unresectable non-squamous NSCLC not amenable to curative surgery or radiation
and/or stage IV NSCLC
- Part 1 (dose-escalation combinations and T-DXd monotherapy): Patients with
therapy-targetable alterations are allowed.
- Part 2 (dose-expansion): Tumors that lack activating EGFR mutations or
EML4-ALK fusion
- Part 1 (dose-escalation combinations and T-DXd monotherapy): Progression on
or after either one or 2 lines of therapy which is required to have included
prior appropriate targeted therapy for patients with therapy-targetable
alterations.
- Part 2 (dose-expansion): treatment-naïve for locally advanced or mNSCLC.
Prior adjuvant, neo adjuvant therapies are permitted if progression has
occurred > 12 months from the end of last therapy
- HER2+ (IHC 3+ or 2+) status as determined by central review of tumor tissue
- WHO / ECOG performance status of 0 or 1
- Has a measurable target disease assessed by the investigator using RECIST 1.1
- Has a protocol defined adequate organ and bone marrow functions
- Has a history of (non-infectious) ILD/pneumonitis that required steroids, has
current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out
by imaging at screening
- Lung criteria:
* Specific intercurrent clinically significant illnesses including, but not
limited to, any underlying pulmonary disorder
* Any auto-immune, connective tissue or inflammatory disorders (eg. Rheumatoid
arthritis, Sjogren*s syndrome, sarcoidosis etc) where this is documented, or a
suspicion of pulmonary involvement at the time of screening.
* Prior pneumonectomy (complete)
- Active primary immunodeficiency known HIV infection, or active hepatitis B or
C infection
- Active infection including tuberculosis and uncontrolled infection requiring
IV antibiotics, antivirals, or antifungals
- Spinal cord compression or clinically active central nervous system
metastases, defined as untreated and symptomatic, or requiring therapy with
corticosteroids or anticonvulsants to control associated symptoms
- Medical history of myocardial infarction within 6 months before treatment
assignment, symptomatic CHF (New York Heart Association Class II to IV),
clinically important cardiac arrhythmias, or a recent (<6 months)
cardiovascular event including stroke
- A pleural effusion, ascites or pericardial effusion that requires drainage,
peritoneal shunt, or CART
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>- To assess the safety and tolerability and to determine the RP2D of T-DXd plus<br /><br>durvalumab in combination with cisplatin, carboplatin or pemetrexed</p><br>
- Secondary Outcome Measures
Name Time Method <p>- To assess the preliminary antitumor activity of T-DXd monotherapy (Part 1<br /><br>only); T-DXd with durvalumab (Part 2 only); and T-DXd plus durvalumab in<br /><br>combination with cisplatin, carboplatin or pemetrexed<br /><br>- To assess the safety and tolerability of T-DXd montherapy (Part 1) and T-DXd<br /><br>plus durvalumab (Part 2)<br /><br>- To assess the PK of T-DXd, total anti-HER2 antibody and MAAA-1181 in all arms<br /><br>- To assess the PK of durvalumab<br /><br>- To investigate the immunogenicity of T-DXd and durvalumab</p><br>