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Phase Ib Study of the Safety of T-DXd and Immunotherapy Agents With and Without Chemotherapy in Advanced or Metastatic HER2+, Non-squamous NSCLC

ConditionLocally Advanced or Metastatic Non-Small Cell Lung Cancer
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorAstraZeneca

About this trial

DESTINY-Lung03 will investigate the safety and tolerability of trastuzumab deruxtecan in combination with Immunotherapy Agents with and without chemotherapy in patients with HER2 over-expressing non-small cell lung cancer. The efficacy will be also analyzed as a secondary endpoint.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Histologically documented unresectable locally advanced/metastatic non-squamous NSCLC

Part 1: Progression after 1 or 2 lines of systemic therapy for recurrent or metastatic setting.

Part 3, Part 4 and Part 5: Patients must have tumors that do not harbor known genomic alterations or actionable driver kinases, for which approved therapies are available are allowed.

Part 3, Part 4 and Part 5: Patient must be treatment-naïve for advanced or metastatic NSCLC. Patients who have received prior adjuvant, or neoadjuvant chemotherapy, or definitive chemoradiation for advanced disease are eligible, provided that progression has occurred > 6 months from end of last therapy

Disqualifiers

HER2 mutation if previously known

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-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 chronic and resolved hepatitis B (positive hepatitis B virus surface antigen [HBsAg+ve] or hepatitis B virus core antibody (anti-HBc +ve) regardless of HBV DNA level)) or hepatitis C infection. Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Patients should be tested for HIV prior to treatment assignment if required by local regulations or IRB/EC

Trial design

Design model

Parallel

Treatments tested in this trial

  • T-DXd

    Drug

    T-DXd: administered as an IV infusion

  • Durvalumab

    Biological/Vaccine

    Durvalumab: administered as an IV infusion

  • Cisplatin

    Drug

    Cisplatin: administered as an IV infusion

  • Carboplatin

    Drug

    Carboplatin: administered as an IV infusion

  • Pemetrexed

    Drug

    Pemetrexed: administered as an IV infusion (drug not used)

  • Volrustomig

    Drug

    Volrustomig: administered as an IV infusion

  • Rilvegostomig

    Drug

    Rilvegostomig: administered as an IV infusion

Treatment groups

304 Participants
are divided into 10 treatment groups

10

Treatment groups

See each treatment group below.

Group A: Arm 1A: T-DXd, Durvalumab and CisplatinExperimental treatment 3 interventions
Group B: Arm 1B: T-DXd, Durvalumab and CarboplatinExperimental treatment 3 interventions
Group C: Arm 1C: T-DXd, Durvalumab and PemetrexedExperimental treatment 3 interventions
Group D: Arm 1D: T-DXdExperimental treatment 1 intervention
Group E: Arm 3A: T-DXd and VolrustomigExperimental treatment 2 interventions
Group F: Arm 3B: T-DXd, Volrustomig and CarboplatinExperimental treatment 3 interventions
Group G: Arm 4A: T-DXd and RilvegostomigExperimental treatment 2 interventions
Group H: Arm 4B T-DXd and Rilvegostomig with CarboplatinExperimental treatment 3 interventions
Group I: Arm 5A: T-DXd and VolrustomigExperimental treatment 2 interventions
Group J: Arm 5B: T-DXd and VolrustomigExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Frequency of AEs and SAEs

Occurrence of AEs and SAEs graded according to NCI CTCAE v5.0

Time frame
Safety and tolerability (and to determine RP2D) will be assessed for approximately 20 months from informed consent

Secondary outcomes

1

Confirmed Objective Response Rate (ORR)

Confirmed ORR per RECIST 1.1 is the percentage of patients with Complete Response or Partial Response that is subsequently confirmed, based on investigator assessment

Time frame
An average of approximately 12 months
2

Duration of Response (DoR)

DOR is defined as the time from the date of first documented response until the date of documented progression or death, based on RECIST 1.1 assessment

Time frame
An average of approximately 20 months
3

Disease Control Rate (DCR)

DCR is the percentage of patients who have a best overall response of complete response (CR) or partial response (PR) or stable disease (SD), based on RECIST 1.1 assessment. DCR is assessed at 6 and 12 weeks

Time frame
An average of approximately 12 months
4

Progression-free survival (PFS)

PFS is the time from first dose of study treatment until the date of objective disease progression or death, based on RECIST 1.1 assessment

Time frame
An average of approximately 20 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

AstraZeneca

Lead sponsor

Daiichi Sankyo

Collaborator

Source ClinicalTrials.gov
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