The Efficacy and Safety of Osimertinib With Platinum Plus Pemetrexed Chemotherapy as First-line Treatment in Advanced Non-small Cell Lung Cancer Patients With Uncommon Epidermal Growth Factor Receptor Mutations: A phase2, Open Label, Single Arm, Multicenter, Exploratory Study (MINOVA)

  • STATUS
    Recruiting
  • End date
    Feb 28, 2025
  • participants needed
    35
  • sponsor
    AstraZeneca
Updated on 18 September 2022
cancer
hysterectomy
measurable disease
lung cancer
pemetrexed
carboplatin
EGFR
osimertinib
lung carcinoma

Summary

This is an open-label, single-arm, multicenter, exploratory Phase II study sponsored by Astrazeneca Investment (China) Co., LTD. to evaluate the efficacy and safety of Osimertinib with Platinum plus Pemetrexed Chemotherapy, as First-line Treatment in Recurrent or Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC) Patients with Uncommon Epidermal Growth Factor Receptor Mutations (EGFRm).

Description

Participants successfully enrolled into the study will receive 80mg osimertinib QD p.o. plus standard chemotherapy composed of cisplatin or carboplatin and pemetrexed i.v. on Day 1 of a 21 day cycle (every 3 weeks) for 4 to 6 cycles, followed by osimertinib 80 mg QD p.o. plus pemetrexed maintenance i.v. every 3 weeks until RECIST 1.1-defined radiological progression as judged by the investigator.

Tumour assessments will be performed as per RECISTv1.1 criteria, using computed tomography (CT)/magnetic resonance imaging (MRI). The baseline assessment is part of the screening procedures and should be performed before the start of study intervention.

safety will be assessed in the whole treatment period as well as 28 days after study drug termination for any reason.

Details
Condition Lung Cancer
Treatment Osimertinib
Clinical Study IdentifierNCT05215951
SponsorAstraZeneca
Last Modified on18 September 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol
Provision of signed and dated, written informed consent form prior to any mandatory study-specific procedures, sampling, and analyses
Male or female, at least 18 years of age
Pathologically confirmed nonsquamous NSCLC
Newly diagnosed locally advanced (clinical stage IIIB, IIIC) or metastatic NSCLC (clinical stage IVA or IVB) or recurrent NSCLC (per Version 8 of the International Association for the Study of Lung Cancer [IASLC] Staging Manual in Thoracic Oncology), not amenable to curative surgery or radiotherapy
The tumour harbors at least 1 of the 4 uncommon EGFR mutations (G719X/L861Q/S768I/T790M), either alone or in combination, which not include other EGFR mutations including ex19del /L858R, assessed by one of ARMS, Super-ARMS or NGS analysis on the basis of tumour tissue or plasma testing from accredited laboratories approved by the Chinese regulatory authority
Participants must be considered suitable by investigator and about to receive standard of care which composed of pemetrexed plus carboplatin or cisplatin for 4 to 6 cycles followed by pemetrexed maintenance
Participants must have untreated advanced NSCLC not amenable to curative surgery or radiotherapy. Prior adjuvant and neo-adjuvant therapies (chemotherapy, radiotherapy, immunotherapy, biologic therapy, investigational agents), or definitive radiation/chemoradiation with or without regimens including immunotherapy, biologic therapy, investigational agents, are permitted as long as treatment was completed at least 6 months prior to the development of recurrent disease
Stable CNS metastases participants will be allowed
ECOG/WHO PS of 0 to 1 at screening with no clinically significant deterioration in the previous 2 weeks
Life expectancy >12 weeks at Day 1
At least 1 lesion, not previously irradiated that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes, which must have a short axis of ≥15 mm) with CT or MRI, and that is suitable for accurate repeated measurements. If only 1 measurable lesion exists, it is acceptable to be used (as a target lesion) as long as it has not been previously irradiated and as long as it has not been biopsied within 14 days of the baseline tumour assessment scans
Female must be using highly effective contraceptive measures, must not be breast feeding, and must have a negative pregnancy test prior to first dose of study intervention or must have evidence of non-child-bearing potential by fulfilling 1 of the following criteria at screening
Post-menopausal, defined as more than 50 years of age and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments
Women under 50 years old would be considered as postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and have luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the post-menopausal range for the institution
Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation. Further information is available in Appendix E (Definition of Women of Childbearing Potential and Acceptable Contraceptive Methods)
Male participants must be willing to use barrier contraception

Exclusion Criteria

Spinal cord compression; symptomatic and unstable brain metastases, except for those
participants who have completed definitive therapy, are not on steroids, and have a stable
neurological status for at least 2 weeks after completion of the definitive therapy and
steroids. Participants with asymptomatic brain metastases can be eligible for inclusion if
in the opinion of the Investigator immediate definitive treatment is not indicated
Past medical history of ILD, drug-induced ILD, radiation pneumonitis that required
steroid treatment, or any evidence of clinically active ILD
Any evidence of severe or uncontrolled systemic diseases, including uncontrolled
hypertension and active bleeding diatheses, which in the Investigator's opinion makes it
undesirable for the participant to participate in the trial or which would jeopardize
compliance with the protocol, or active infection including any patients receiving
treatment for infection but not limited to hepatitis B, hepatitis C and human
immunodeficiency virus (HIV). Screening for chronic conditions is not required
Any of the following cardiac criteria
Mean resting corrected QT interval (QTc) >470 msec, obtained from 3 electrocardiograms
(ECGs), using the screening clinic ECG machine-derived QTcF value
Any clinically important abnormalities in rhythm, conduction, or morphology of resting
ECG; eg, complete left bundle branch block, third-degree heart block, second-degree
heart block
Any factors that increase the risk of QTc prolongation or risk of arrhythmic events
such as electrolyte abnormalities including serum/plasma potassium _, magnesium_ and
calcium below the lower limit of normal (LLN), heart failure, congenital long QT
syndrome, family history of long QT syndrome, or unexplained sudden death under 40
years of age in first-degree relatives or any concomitant medication known to prolong
the QT interval and cause Torsades de Pointes
Inadequate bone marrow or organ function reserve as demonstrated by any of the
following laboratory values
Absolute neutrophil count below the LLN
Platelet count below the LLN
Hemoglobin <90 g/L The use of granulocyte colony stimulating factor support
platelet transfusion and blood transfusions to meet these criteria is not permitted
ALT >2.5 x the upper limit of normal (ULN) if no demonstrable liver metastases or >5 x
ULN in the presence of liver metastases
AST >2.5 x ULN if no demonstrable liver metastases or >5 x ULN in the presence of
liver metastases
Total bilirubin >1.5 x ULN if no liver metastases or >3 x ULN in the presence of
documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases
Creatinine clearance <60 mL/min calculated by Cockcroft and Gault equation (refer to
Appendix G for appropriate calculation) 6.Any concurrent and/or other active
malignancy that has required treatment within 2 years of first dose of study
intervention (osimertinib, carboplatin and pemetrexed)
Any unresolved toxicities from prior therapy (eg, adjuvant chemotherapy) greater
than CTCAE Grade 1 at the time of starting study treatment, with the exception of
alopecia and Grade 2 prior platinum-therapy related neuropathy. 8 Refractory nausea
and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated
product, or previous significant bowel resection that would preclude adequate
absorption of osimertinib
Prior treatment with any systemic anti-cancer therapy for advanced NSCLC not
amenable to curative surgery or radiation including chemotherapy, biologic therapy
immunotherapy, or any investigational drug. Prior adjuvant and neo-adjuvant therapies
(chemotherapy, radiotherapy, biologic therapy, investigational agents), or definitive
radiation/chemoradiation with or without regimens including biologic therapies
investigational agents are permitted as long as treatment was completed at least 6
months prior to the development of recurrent disease
Prior treatment with an EGFR-TKI or immune-oncology (IO) therapy. 11.Major surgery
within 4 weeks of the first dose of study intervention. Procedures such as placement
of vascular access, biopsy via mediastinoscopy or biopsy via video assisted
thoracoscopic surgery (VATS) are permitted
Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of
radiation within 4 weeks of the first dose of study intervention
Current use of (or unable to stop use prior to receiving the first dose of study
treatment) medications or herbal supplements known to be strong inducers of cytochrome
P450 (CYP) 3A4 (at least 3 weeks prior) (Appendix F). All patients must try to avoid
concomitant use of any medications, herbal supplements and/or ingestion of foods with
known inducer effects on CYP3A4
Participation in another clinical study with an investigational product during the
weeks prior to Day 1. Participants in the follow-up period of an interventional
study are permitted
Involvement in the planning and/or conduct of the study (applies to both
AstraZeneca staff and staff at the study site)
Judgment by the Investigator that the participant should not participate in the
study if the participant is unlikely to comply with study procedures, restrictions and
requirements
Previously enrolled in the present study. 18.Currently pregnant (confirmed with
positive pregnancy test) or breast-feeding
History of hypersensitivity to active or inactive excipients of study intervention
or drugs with a similar chemical structure or class to study intervention
In addition, the following conditions are considered criteria for exclusion
Prior allogeneic bone marrow transplant
Non-leukocyte depleted whole blood transfusion within 120 days of genetic sample
collection
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