Clinical trial NCT05801029: A Study to Investigate Safety and Efficacy of Osimertinib and Amivantamab in Participants With Non-small Cell Lung Cancer With Common Epidermal Growth Factor Receptor Mutations
Official title: A Phase II, Open-label, Single-arm, Multi-centre Study to Evaluate the Safety and Efficacy of Osimertinib With Amivantamab as First-line Treatment in Participants With Epidermal Growth Factor Receptor Mutation-Positive, Locally Advanced or Metastatic Non-small Cell Lung Cancer (OSTARA)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer (NSCLC)
Keywords: NSCLC
Non squamous
Epidermal Growth Factor Receptor (EGFR)
Epidermal Growth Factor Receptor mutation (EGFRm)
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2023-04-06
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will assess the safety and efficacy of Osimertinib with Amivantamab as First-line Treatment in Participants with Epidermal Growth Factor Receptor Mutation-Positive, Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC).

Detailed description: This is a Phase II, open-label, single-arm, multi-centre study to assess the safety and efficacy of osimertinib with amivantamab as first-line treatment in adult participants with a local preexisting positive approved tissue test result for EGFRm (Ex19del or L858R), locally advanced (clinical stage IIIB, IIIC), metastatic (clinical stage IVA or IVB), or recurrent non-squamous NSCLC.

This study consists of screening period of 28 days, followed by the study intervention period wherein the participant receives treatment from Day 1 until disease progression or study intervention discontinuation. Participants will be followed up at week 6 (± 1 week), week 12 (± 1 week), then every 12 weeks (± 1 week) until radiological disease progression. Survival follow up will be performed every 12 weeks. Upon study intervention discontinuation a 28 day follow up visit will be performed.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically documented non-squamous NSCLC. NSCLC of mixed histology is allowed.
* Newly diagnosed locally advanced or metastatic NSCLC or recurrent non-squamous NSCLC, not amenable to curative surgery or radiotherapy.
* WHO PS of 0 to 1 with no deterioration over the 2 weeks prior to enrolment.
* Minimum life expectancy \> 12 weeks at Day 1.
* Confirmation by the local laboratory that the tumour harbours one of the 2 common EGFRm known to be associated with (Epidermal Growth Factor Receptor- Tyrosine Kinase Inhibitor) EGFR-TKI sensitivity.
* At least 1 lesion that can be accurately measured at baseline as ≥10 mm in the longest diameter with computed tomography (CT) or magnetic resonance imaging (MRI) and that is suitable for accurate repeated measurements.
* Contraceptive use by males or females should be consistent with local regulations

Exclusion Criteria:

* Any evidence of diseases, history of allogenic organ transplant, which in the investigator's opinion makes it undesirable for the participant to participate in the study or would jeopardise compliance with protocol.
* Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the osimertinib, or previous significant bowel resection that would preclude adequate absorption distribution, metabolism, or excretion of osimertinib.
* History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥2 years.
* Any unresolved toxicities from prior therapy with Common Terminology Criteria for Adverse Events CTCAE) Grade ≥1, at the time of first dose of study intervention, with the exception of alopecia and Grade 2 prior platinum therapy related neuropathy.
* Spinal cord compression or brain metastases unless asymptomatic, stable, and not requiring corticosteroids for at least 2 weeks prior to start of study intervention.
* Active infection, including tuberculosis and infections with HBV (verified by known positive HBsAg result) or HCV.
* Should participants with HIV infection be included, patients are only eligible if they meet the criteria per protocol.
* Patient with protocol defined cardiac issue.
* History of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically active ILD.
* Any concomitant medications known to be associated with Torsade de Pointes.
* Prior exposure to any systemic anti-cancer therapy for advanced NSCLC not amenable to curative surgery or radiation including chemotherapy, biologic therapy, immunotherapy, or any investigational drug.
* Any concurrent anti-cancer treatment without an adequate washout period prior to the first dose of study intervention.
* Palliative radiotherapy with a limited field of radiation within 2 weeks, or with wide field of radiation or to more than 30% of the bone marrow within 4 weeks, prior to the first dose of study intervention.
* Major surgical procedure or significant traumatic injury.
* Current use of medications or herbal supplements known to be strong inducers of CYP 3A4.
* Prior treatment with an EGFR-TKI.
* Participants with a history of hypersensitivity, or intolerance to the active or inactive excipients of osimertinib, amivantamab, or recommended pre-treatments of amivantamab or drugs with a similar chemical structure or class to these drugs.

Primary outcomes:
measure: Number of participants with adverse events (AEs)
timeFrame: From screening (Day-28) to survival follow up (Approximately 52 months after the first participant is dosed)
measure: Progression Free Survival (PFS)
timeFrame: From date of first dose of study intervention until radiological disease progression or death due to any cause (Approximately 52 months after the first participant is dosed)
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From date of first dose of study intervention until death due to any cause. Landmarks at 18 and 24 months. (Approximately 52 months after the first participant is dosed)
measure: Objective Response Rate (ORR)
timeFrame: From screening (Day -28) to radiological disease progression (Approximately 52 months after the first participant is dosed)
measure: Duration of Response (DoR)
timeFrame: From screening (Day -28) to radiological disease progression (Approximately 52 months after the first participant is dosed)
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Research Site
city: Hong Kong
country: Hong Kong
facility: Research Site
city: Hong Kong
country: Hong Kong
facility: Research Site
city: Shatin
country: Hong Kong
facility: Research Site
city: Anyang-si
country: Korea, Republic of
facility: Research Site
city: Busan
country: Korea, Republic of
facility: Research Site
city: Daegu
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: George Town
country: Malaysia
facility: Research Site
city: Kota Bharu
country: Malaysia
facility: Research Site
city: Kuala Lumpur
country: Malaysia
facility: Research Site
city: Kuala Lumpur
country: Malaysia
facility: Research Site
city: Kuantan
country: Malaysia
facility: Research Site
city: Kuching
country: Malaysia
facility: Research Site
city: Singapore
country: Singapore
facility: Research Site
city: Singapore
country: Singapore
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Tainan
country: Taiwan
facility: Research Site
city: Taipei City
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Yunlin
country: Taiwan
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Chiang Mai
country: Thailand
facility: Research Site
city: Songkhla
country: Thailand
facility: Research Site
Study officials:
References: