Phase Ib Study of the Safety of T-DXd and Durvalumab With Chemotherapy in Advanced or Metastatic HER2+ Non-squamous NSCLC

Trial number:
NCT04686305
Trial phase:
1
Study type:
Immunotherapy, Targeted therapy, Chemotherapy
Overall status:
Recruiting

Study start date

March, 2021

Scientific title

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)

Summary

DESTINY-Lung03 will investigate the safety and tolerability of trastuzumab deruxtecan in combination with durvalumab and chemotherapy in patients with HER2 positive advanced and metastatic non-small cell lung cancer. The efficacy will be also analyzed as a secondary endpoint.

Inclusion criteria:

Histologically documented unresectable locally advanced/metastatic non-squamous NSCLCPart 1: Progression after 1 or 2 lines of systemic therapy for recurrent or metastatic setting. Part 2: Treatment-naïve for non curative treatment for locally advanced or metastatic NSCLC. Part 2: Patients must have tumors that lack activating EGFR mutations, EML4-ALK fusion or other targetable alterations. Prior adjuvant, neoadjuvant therapies are permitted if progression has occurred > 12 months from the end of last therapy HER2+ (IHC 3+ or IHC 2+) status as determined by central review of tumor tissue WHO / ECOG performance status of 0 or 1 Measurable target disease assessed by the investigator using RECIST 1.1 Has protocol defined adequate organ and bone marrow function

Exclusion criteria:

HER2 mutation if previously knownHas 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-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder and prior pneumonectomy 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 (Concentrated Ascites Reinfusion Therapy) Unresolved toxicities from previous anticancer therapy OR prior discontinuation of any planned study therapy due to toxicity.

Study design

Primary purpose: Treatment, Allocation: Non-Randomized, Intervention model: Parallel Assignment, Intervention model description: The study will consist of 2 parts:, , Dose-escalation part and monotherapy arm (Part 1; second-line and third-line patients): The dose of T-DXd and chemotherapeutic components on Arms 1A, 1B and 1C (cisplatin, carboplatin or pemetrexed) will be modified during the dose-escalation part in order to find the RP2D. Durvalumab dose will remain fixed on the dose escalation part of the study. Arm 1D is the T-DXd monotherapy arm., Dose-expansion part (Part 2; treatment naïve patients for metastatic disease): may be initiated following dose escalation at the discretion of the sponsor., , In addition to safety and tolerability, the study will also assess preliminary efficacy based upon ORR, DoR, DCR, OS, PFS among treatment groups. , Masking: None (Open Label),

Conditions

Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Other study ID numbers

D967YC00001

Choose trial site (77)

National Cancer Centre Singapore
Tan Tock Seng Hospital Singapore
8 May Rd, Singapore 328595