Osimertinib Plus Chemotherapy in Uncommon EGFRm NSCLC

NCT05215951 | Terminated Phase 2 Results

• 1 other identifier: D5161C00017
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 6

Brief 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).

Conditions

Lung Cancer

Outcome Measures

Primary Outcomes (1)

• ORR

  ORR (objective response rate) defined as the percentage of participants who achieved a complete response (CR) or partial response (PR) as their best overall response based on Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 as assessed by the investigator

  Due to study early terminated, actual time frame is up to 24 weeks.

Secondary Outcomes (8)

• PFS

  Due to study early terminated, actual time frame is up to approximately 12 months.

• OS

  Due to study early terminated, actual time frame is up to approximately 13 months.

• DoR

  Due to study early terminated, actual time frame is up to approximately 12 months.

• Depth of Response (Best Absolute Change in Target Lesion Tumour Size From Baseline)

  Due to study early terminated, actual time frame is up to approximately 12 months.

• DCR

  Due to study early terminated, actual time frame is up to approximately 12 months.

Study Arms (1)

Osimertinib plus standard chemotherapy

EXPERIMENTAL

single-arm

Drug: osimertinib

Interventions

osimertinib DRUG

Dose Formulation: tablet； Dosage Level(s): osimertinib 80 mg QD for oral administration; Dosage formulation, dose reduction:40 mg QD for oral administration

Also known as: AZD9291, Tagrisso

Osimertinib plus standard chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (6)

Research Site

Chengdu, 610041, China

Location

Research Site

Harbin, 150049, China

Location

Research Site

Mianyang, 621000, China

Location

Research Site

Nanchong, 637000, China

Location

Research Site

Yibin, 644000, China

Location

Research Site

Zhengzhou, 450000, China

Location

Related Links

• Redacted Clinical Study Protocol
• Redacted Statistical Analysis Plan (SAP)
• Redacted CSR synopsis

MeSH Terms

Conditions

Lung Neoplasms

Interventions

osimertinib

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

Enrollment to study D5161C00017 was terminated prior to completion of the study due to the delay in study enrollment. Due to the early termination of the study, only 4 participants (of the planned 35 participants) received study intervention and data collection for these participants was limited.

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• You Lu, Doctor

  West China Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2021
• First Posted: January 31, 2022
• Study Start: January 19, 2022
• Primary Completion: March 9, 2023
• Study Completion: March 9, 2023
• Last Updated: October 15, 2025
• Results First Posted: October 15, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

CN (6)