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Non-squamous NSCLCPhase 2NCT05751187

Pembrolizumab Plus Bevacizumab and Chemotherapy for Non-Squamous NSCLC Patients

A Phase 2 study testing Pembrolizumab, Bevacizumab and Pemetrexed in people with Non-squamous NSCLC, run by Shanghai Chest Hospital at 1 site in China.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This study is designed to evaluate the efficacy and safety of Pembrolizumab in combination with Bevacizumab and chemotherapy in advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutation. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Non-squamous NSCLC
What is being tested?
Pembrolizumab, Bevacizumab and Pemetrexed
Could I receive a placebo?
No, everyone receives an active treatment
How many people
54 participants
Where
1 siteChina
Study dates
27 Jun 2023to 30 Dec 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • According to the 8th edition of the AJCC/UICC TNM staging system for NSCLC, patients with locally advanced (stage III B/III C), metastatic or recurrent (stage IV) nonsquamous NSCLC confirmed by histology or cytology who are unable to undergo surgery and radical concomitant radiochemotherapy and are confirmed to have at least one measurable lesion according to RECIST 1.1.
  • Patients harboring exon 20 insertions detected by ARMS or NGS or other approved methods.
  • Age ≥18 years and ≤75 years.
  • ECOG PS score: 0 to 1
  • Have a life expectancy of at least 3 months.
  • Have not received prior systemic treatment including chemotherapy, checkpoint inhibitors, TKIs, and anti-angiogenesis agents for their advanced/metastatic NSCLC. Subjects who received adjuvant or neoadjuvant therapy including immunotherapy are eligible if the adjuvant/neoadjuvant therapy was completed at least 12 months prior to the development of advanced/metastatic disease. Palliative radiotherapy must be completed 7 days before the first dose of study drugs and participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
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  • Have adequate organ function as defined in the following： (1) Adequate bone marrow function Absolute neutrophil count(ANC) ≥ 1500/uL; Platelets≥10x104/uL; Hemoglobin ≥9.0g/dL or ≥5.6 mmol/L; (2) Adequate kidney function Creatinine≤ 1.5 x upper normal limit (ULN), OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≥30 mL/min for the participant with creatinine levels >1.5 × institutional ULN (3) Adequate liver function Total bilirubin ≤ 1.5 x upper normal limit (ULN) OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN; Aspartate Aminotransferase (AST) (SGOT) ≤ 2.5 xULN (≤ 5.0 x ULN if hepatic metastases); Alanine Aminotransferase (ALT) (SGPT) ≤ 2.5 x ULN (≤ 5.0x ULN if hepatic metastases); (4) Coagulation function International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless the participant is receiving anticoagulant therapy as long as PT or aPTT is within the therapeutic range of intended use of anticoagulants.
  • A male participant must agree to use contraception during the treatment period and plus an additional 90 days (a spermatogenesis cycle) for study treatments after the last dose of study treatment and refrain from donating sperm during this period; A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: a. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR b. A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and plus 30 days (a menstruation cycle) for study treatments after the last dose of study treatment.
  • The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
  • Archival tumor tissue sample or newly obtained [core, incisional, or excisional] biopsy of a tumor lesion not previously irradiated has been provided. Formalin-fixed, paraffin-embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
  • For hepatitis B-positive subjects:
  • Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have an undetectable HBV viral load prior to enrollment.
  • Participants should remain on anti-viral therapy throughout the study intervention and follow local guidelines for HBV anti-viral therapy post-completion of the study intervention.
  • Participants with a history of HCV infection are eligible if HCV viral load is undetectable at screening.
  • Participants must have completed curative anti-viral therapy at least 4 weeks prior to enrollment.

Who cannot join

  • Small cell lung cancer (including mixed small cell and non-small cell lung cancer);
  • Patients who have received systemic treatment for advanced/metastatic disease especially have received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g, CTLA-4, OX 40, CD137);
  • Patients concurrently with 19del or 21L858R or other mutation types located in exon 18-21
  • Patients who are known to have active brain metastases diagnosed by CT or MRI at the time of screening, however, participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without the requirement of steroid treatment for at least 14 days prior to the first dose of the study intervention.;
  • Patients with severe and/or uncontrolled diseases, such as:
  • Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months before randomization, severe uncontrolled arrhythmias; uncontrolled blood pressure (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg); (2) Active or uncontrolled serious infection; (3) Liver diseases such as cirrhosis, decompensated liver disease, acute or chronic active hepatitis; (4) Not completely controlled eye inflammation or eye infection, or any condition that may lead to the above-mentioned ocular diseases (5) Poorly controlled diabetes (fasting blood glucose (FBG) > 10mmol/L); (6) Routine urine test result indicates that urine protein ≥++, and 24-hour urine protein quantitation is confirmed to be > 1.0 g; (7) Active tuberculosis, etc.; (8) Uncontrolled hypercalcemia (> 1.5 mmol/L calcium ion or calcium > 12 mg/dL or corrected serum calcium > ULN), or symptomatic hypercalcemia requiring continued diphosphate therapy; (9) Long-term unhealed wounds or fractures; 6. Patients who have a history of psychotropic drug abuse and cannot abstain from it or have mental disorders; 7. Patients who are known to have severe allergies (≥ grade 3) to active ingredients and any excipients of pembrolizumab 8. Patients who have other malignant tumors (except radical cervical carcinoma in situ, non-melanoma skin cancer, etc.) at the same time; patients who are evaluated by the investigator to have concomitant diseases that seriously endanger the safety of the patients or affect the patients completing the study.
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  • 9. The subjects or their sexual partners cannot or refuse to take effective contraceptive measures during the clinical trial 10. Pregnant or breast-feeding women 11. Patients in other situations who are evaluated by the investigator to be ineligible to be enrolled; 12. Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of the study intervention. Administration of killed vaccines is allowed (such as COVID-19 vaccines).
  • 13. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of the study drug.
  • 14. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with the use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
  • 15. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
  • 16. Has a known history of Human Immunodeficiency Virus (HIV) infection. 17. Has a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
  • 18. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • 19. Has had an allogeneic tissue/solid organ transplant. 20. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to administration of pembrolizumab.
  • 21. Patients who have contraindications of antiangiogenic therapy, including the presence of cavities, and bleeding tendencies judged by the treating physician.

Trial locations and contacts

1 site in 1 country.

China1 site

  • Shanghai Chest Hospital

    Shanghai

Other trials in China

About this study

Official title: Pembrolizumab Plus Bevacizumab and Chemotherapy as First-Line Treatment for Advanced or Metastatic Non-Squamous NSCLC Patients With EGFR Exon 20 Insertion Mutation: An Open-Label, Single-Arm, Phase II Trial

This study is designed to evaluate the efficacy and safety of Pembrolizumab in combination with Bevacizumab and chemotherapy in advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutation.

Keywords
EGFR exon 20 insertion

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabBiological

    Pembrolizumab was given as 200 milligrams (mg) via intravenous (IV) infusion over 30 minutes on Day 1 of each 21-day cycle.

  • BevacizumabBiological

    Bevacizumab was given as 15 mg/kg via intravenous (IV) infusion on Day 1 of each 21-day cycle.

  • PemetrexedDrug

    Pemetrexed was given as 500 mg/m^2 via intravenous (IV) infusion (with vitamin supplementation) on Day 1 of each 21-day cycle for 4-6 cycles.

  • CisplatinDrug

    Cisplatin was given as 75 mg/m^2 via intravenous (IV) infusion (administered approximately 30 minutes after pemetrexed infusion) on Day 1 of each 21-day cycle for 4-6 cycles.

  • CarboplatinDrug

    Carboplatin was given as Aare Under the Curve (AUC) 5 (5 mg/mL/min; over 15-60 min) via intravenous (IV) infusion (administered immediately after pemetrexed infusion) on Day 1 of each 21-day cycle for 4-6 cycles.

  • Folic acid 350-1000 μgDietary supplement

    Orally; at least 5 doses of folic acid must be taken during the 7 days preceding the first dose of pemetrexed, and folic acid dosing must continue during the full course of therapy and for 21 days after the last dose of pemetrexed.

  • Vitamin B12 1000 μgDietary supplement

    Intramuscular injection in the week preceding the first dose of pemetrexed and once every 3 cycles thereafter. Subsequent vitamin B12 injections may be given on the same day as pemetrexed administration.

  • Dexamethasone 4 mgDrug

    For prophylaxis; orally twice per day (or equivalent). Taken the day before, the day of, and the day after pemetrexed administration.

Study groups in NCT05751187
Study groupRoleWhat they receive
Pembrolizumab + Bevacizumab + ChemotherapyExperimentalParticipants receive pembrolizumab 200 mg intravenously (IV) PLUS pemetrexed 500 mg/m^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m^2 IV OR carboplatin Area Under the Curve (AUC) 5 IV on Day 1 of every 3-week cycle (Q3W) for 4-6 cycles followed by pembrolizumab 200 mg IV PLUS pemetrexed 500 mg/m^2 IV Q3W until progression.
Receives: Biological: Pembrolizumab; Biological: Bevacizumab; Drug: Pemetrexed; Drug: Cisplatin; Drug: Carboplatin; Dietary Supplement: Folic acid 350-1000 μg; Dietary Supplement: Vitamin B12 1000 μg; Drug: Dexamethasone 4 mg

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Response Rate (ORR)

    ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per Response Criteria in Solid Tumors version 1.1 (RECIST 1.1).

    Measured: Up to approximately 24 months

Secondary outcomes (5)

  1. Progression-Free Survival (PFS)

    PFS is defined as the time from the first dose of study treatment to the first documented progressive disease (PD) per Response Criteria in Solid Tumors version 1.1 (RECIST 1.1) based on blinded independent central review (BICR), or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of ≥1 new lesion was also considered PD.

    Measured: Up to approximately 24 months

  2. Overall Survival (OS)

    OS was defined as the time from the first dose of study treatment to death due to any cause.

    Measured: Up to approximately 24 months

  3. Duration of Response (DOR)

    For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from the first documented evidence of a CR or PR until PD or death. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. DOR assessments were based on BICR with confirmation. The DOR per RECIST 1.1 for all participants who experienced a confirmed CR or PR is presented.

    Measured: From time of first documented evidence of CR or PR to Up to approximately 24 months

  4. Number of Participants Who Experienced an Adverse Event (AE)

    An AE was defined as any untoward medical occurrence in a participant-administered study treatment that did not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE is presented.

    Measured: Up to approximately 24 months

  5. Number of Participants Who Discontinued Any Study Drug Due to an AE

    The number of participants who discontinued any randomized study drug due to an AE is presented.

    Measured: Up to approximately 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Mar 2023
  2. Study start27 Jun 2023
  3. Primary completion15 Dec 2025
  4. Study completion30 Dec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
54 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05751187
Sponsor's protocol ID
IS22087
Status last verified
Mar 2026
First submitted
20 Feb 2023
Last updated
11 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Chen K, Pan G, Cheng G, Zhang F, Xu Y, Huang Z, Fan Y. Immune microenvironment features and efficacy of PD-1/PD-L1 blockade in non-small cell lung cancer patients with EGFR or HER2 exon 20 insertions. Thorac Cancer. 2021 Jan;12(2):218-226. doi: 10.1111/1759-7714.13748. Epub 2020 Nov 18.

    PubMed 33210451

  • Dong ZY, Zhang JT, Liu SY, Su J, Zhang C, Xie Z, Zhou Q, Tu HY, Xu CR, Yan LX, Li YF, Zhong WZ, Wu YL. EGFR mutation correlates with uninflamed phenotype and weak immunogenicity, causing impaired response to PD-1 blockade in non-small cell lung cancer. Oncoimmunology. 2017 Jul 26;6(11):e1356145. doi: 10.1080/2162402X.2017.1356145. eCollection 2017.

    PubMed 29147605

  • Lu S, Wu L, Jian H, Chen Y, Wang Q, Fang J, Wang Z, Hu Y, Sun M, Han L, Miao L, Ding C, Cui J, Li B, Pan Y, Li X, Ye F, Liu A, Wang K, Cang S, Zhou H, Sun X, Ferry D, Lin Y, Wang S, Zhang W, Zhang C. Sintilimab plus bevacizumab biosimilar IBI305 and chemotherapy for patients with EGFR-mutated non-squamous non-small-cell lung cancer who progressed on EGFR tyrosine-kinase inhibitor therapy (ORIENT-31): first interim results from a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. 2022 Sep;23(9):1167-1179. doi: 10.1016/S1470-2045(22)00382-5. Epub 2022 Jul 28.

    PubMed 35908558

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab, Bevacizumab and Pemetrexed in people with Non-squamous NSCLC, run by Shanghai Chest Hospital at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 11 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (ORR) (time frame: Up to approximately 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05751187, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Mar 2026.

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