What side effects are associated with this type of intervention?

Common treatments for Non-Small Cell Lung Cancer (NSCLC) include chemotherapy, targeted therapy, and immunotherapy. Chemotherapy often causes side effects such as nausea, vomiting, hair loss, fatigue, and increased risk of infection. Targeted therapies, which act on specific molecular targets, can lead to side effects like skin rash, diarrhea, and liver toxicity. Immunotherapy, which boosts the body's immune system to fight cancer, may cause immune-related side effects such as inflammation of the lungs (pneumonitis), liver (hepatitis), and other organs, as well as fatigue and skin reactions.

What prior FDA approvals exist?

Several FDA-approved treatments for Non-Small Cell Lung Cancer (NSCLC) include antiangiogenic therapies such as bevacizumab and ramucirumab, which inhibit blood vessel growth in tumors. Immune checkpoint inhibitors like pembrolizumab, nivolumab, and atezolizumab have also been approved, targeting PD-1/PD-L1 pathways to enhance the immune system's ability to fight cancer. Additionally, chemotherapy combinations such as carboplatin with pemetrexed or nab-paclitaxel are commonly used. These treatments reflect a range of mechanisms, including antiangiogenesis, immune modulation, and cytotoxic chemotherapy, similar to those being studied in the trial with multiple study treatments.

What other types of research exist?

Promising novel alternatives for NSCLC patients in 2024 include: 1) Targeted therapies such as tyrosine kinase inhibitors (TKIs) for specific mutations (e.g., EGFR, KRAS), 2) Immunotherapies including PD-1/PD-L1 inhibitors (e.g., nivolumab, pembrolizumab, atezolizumab), 3) Combination therapies involving chemotherapy and immunotherapy, and 4) Emerging agents like vinflunine in combination with other biologic agents. These treatments offer hope for improved outcomes and are being actively investigated in clinical trials.

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Tyrosine Kinase Inhibitor

Multiple Therapies for Non-Small Cell Lung Cancer (ORCHARD Trial)

Phase 2

Waitlist Available

Led By Helena A Yu, MD

Research Sponsored by AstraZeneca

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

NSCLC with locally advanced or metastatic disease not amenable to curative surgery or radiotherapy at study entry

Evidence of radiological disease progression on first-line monotherapy with osimertinib 80 mg po QD

Must not have

Inadequate bone marrow reserve or organ function as demonstrated by specific laboratory values

Toxicity(-ies) that led to permanent discontinuation or dose reduction of prior osimertinib

Timeline

Screening 3 weeks

Treatment Varies

Follow Up continuously from first dose to end of safety follow up after study treatment discontinuation (approximately up to 21 months)

Awards & highlights

Summary

This trial is testing several new treatments for patients with advanced lung cancer that has worsened after previous treatments. The goal is to find out if these new treatments can help when current medications stop working.

Who is the study for?

This trial is for adults with advanced non-small cell lung cancer that has worsened despite first-line treatment with Osimertinib. Participants must have a specific EGFR mutation, measurable disease progression, and be able to undergo a biopsy. They should only have had Osimertinib as their prior therapy and not have experienced severe side effects or rapid disease progression on it.

What is being tested?

The study tests the effectiveness of various treatments like Pemetrexed, Datopotamab deruxtecan, Alectinib, among others in patients whose cancer progressed after initial Osimertinib therapy. It's designed to assess multiple treatments' safety and how well they work in different modules.

What are the potential side effects?

Potential side effects include reactions at the infusion site, fatigue, nausea, blood count changes leading to increased infection risk or bleeding tendencies. Organ-specific inflammation may occur depending on which drug is used.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My lung cancer cannot be cured with surgery or radiation.

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My cancer has worsened despite taking osimertinib.

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My lung cancer has EGFR mutations sensitive to specific treatments.

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My tumor can be biopsied, and I am in stable health.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My blood tests show my bone marrow or organs are not working well.

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I stopped or reduced osimertinib due to side effects.

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My condition worsened within 3 months of starting osimertinib.

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I stopped taking osimertinib more than 60 days ago.

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I have side effects from previous osimertinib treatment that are not severe.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ continuously from first dose to end of safety follow up after study treatment discontinuation (approximately up to 21 months)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~continuously from first dose to end of safety follow up after study treatment discontinuation (approximately up to 21 months)

This trial's timeline: 3 weeks for screening, Varies for treatment, and continuously from first dose to end of safety follow up after study treatment discontinuation (approximately up to 21 months) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Objective response rate (ORR)

Secondary study objectives

Duration of response (DoR)

Incidence of Treatment-emergent adverse events (AEs) and serious adverse events (SAEs) as characterized and graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event [CTCAE] v5

Overall survival (OS)

+2 more

Side effects data

From 2020 Phase 4 trial • 60 Patients • NCT03853551

10%

Blood creatine phosphokinase increased

10%

Fatigue

Decreased appetite

Diarrhoea

Cough

Mucosal inflammation

Rash

Pain in extremity

Constipation

Thrombocytopenia

Paronychia

Dyspnoea

Dengue fever

Disease progression

Cardio-respiratory arrest

Cataract

Mouth Ulceration

Deep Vein Thrombosis

100%

80%

60%

40%

20%

Study treatment Arm

Single Arm

Trial Design

11Treatment groups

Experimental Treatment

Active Control

Group I: Module 9: Osimertinib + SelumetinibExperimental Treatment2 Interventions

The patients in this group will receive osimertinib taken in combination with selumetinib

Group II: Module 8: Osimertinib + Pemetrexed + Carboplatin or Cisplatin.Experimental Treatment4 Interventions

The patients in this group will receive Osimertinib plus platinum-containing doublet (pemetrexed + carboplatin or cisplatin).

Group III: Module 7: Etoposide + Durvalumab + Carboplatin or CisplatinExperimental Treatment4 Interventions

The patients in this group will receive platinum-containing doublet (etoposide + carboplatin or cisplatin) taken in combination with durvalumab.

Group IV: Module 6: Osimertinib + SelpercatinibExperimental Treatment2 Interventions

The patients in this group will receive osimertinib taken in combination with selpercatinib

Group V: Module 5: Osimertinib + AlectinibExperimental Treatment2 Interventions

The patients in this group will receive osimertinib taken in combination with alectinib

Group VI: Module 4: Carboplatin + Pemetrexed + Durvalumab)Experimental Treatment3 Interventions

The patients in this group will receive platinum-containing doublet (carboplatin + pemetrexed) taken in combination with durvalumab.

Group VII: Module 3: Osimertinib + NecitumumabExperimental Treatment2 Interventions

The patients in this group will receive osimertinib taken in combination with necitumumab

Group VIII: Module 2: Osimertinib + GefitinibExperimental Treatment2 Interventions

The patients in this group will receive osimertinib taken in combination with gefitinib

Group IX: Module 1: Osimertinib + SavolitinibExperimental Treatment2 Interventions

The patients in this group will receive osimertinib taken in combination with savolitinib

Group X: Module 10: Osimertinib + datopotamab deruxtecanExperimental Treatment2 Interventions

The patients in this group will receive osimertinib taken in combination with datopotamab deruxtecan.

Group XI: Observational Cohort: No study drugActive Control1 Intervention

Patients in this group will not receive study treatment but receive further anticancer care (Standard of Care therapy or other experimental therapies) or supportive care, as clinically indicated, in accordance with local practice. With Group C, the aim is to understand the clinical course and/or outcome for the overall clinical population after progression on first-line monotherapy with osimertinib.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Selumetinib

2010

Completed Phase 2

~2080

Savolitinib

2024

Completed Phase 1

~120

Carboplatin

2014

Completed Phase 3

~6120

Pemetrexed

2014

Completed Phase 3

~5550

Gefitinib

2005

Completed Phase 3

~2440

Necitumumab

2013

Completed Phase 3

~2480

Alectinib

2015

Completed Phase 3

~2400

Durvalumab

2017

Completed Phase 2

~3840

Selpercatinib

2021

Completed Phase 1

~600

Etoposide

2010

Completed Phase 3

~2960

Cisplatin

2013

Completed Phase 3

~2360

Osimertinib

2017

Completed Phase 4

~1100

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Non-Small Cell Lung Cancer (NSCLC) include chemotherapy, targeted therapy, and immunotherapy. Chemotherapy agents like cisplatin and etoposide kill rapidly dividing cancer cells. Targeted therapies, such as osimertinib for EGFR mutations, block specific molecular pathways crucial for tumor growth. Immunotherapy, including PD-1/PD-L1 inhibitors like pembrolizumab, boosts the immune system's ability to detect and destroy cancer cells. These treatments are vital for NSCLC patients as they provide personalized and effective options that can enhance survival and quality of life.

The management of non-small-cell lung cancer: a case history.