A Study to Evaluate PK, Efficacy, and Safety of BAT3306 Plus Chemo and Compare With Keytruda®(EU/US) in Participants With IV nqNSCLC.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Bio-Thera Solutions Ltd.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

16 Oct 2024 → 9 Jun 2025

Decision date (initial)

2024-07-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-510640-32-00

ClinicalTrials.gov

NCT06280196

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Bioequivalence, Pharmacokinetic, Efficacy, Safety

1. To compare the pairwise PK (Pharmacokinetic)similarities between BAT3306 and EU-Keytruda®, BAT3306 and US-Keytruda®, and between EU-Keytruda® and US-Keytruda® in participants with nsNSCLC
2. To compare the efficacy of BAT3306 and EU-Keytruda® and US-Keytruda® given with chemotherapy as first line treatment using ORR assessed by BIRC to show clinical equivalence in participants with nsNSCLC

Secondary objectives 6

1. To evaluate the PK characteristics of BAT3306, EU-Keytruda®, and US-Keytruda® in participants with nsNSCLC
2. To evaluate the PK characteristics of BAT3306 and EU-Keytruda® and US-Keytruda® in participants with nsNSCLC
3. To evaluate the safety and tolerability of BAT3306 and EU-Keytruda® and US-Keytruda® in participants with nsNSCLC
4. To evaluate the immunogenicity of BAT3306 and EU-Keytruda® and US-Keytruda® in participants with nsNSCLC
5. To further evaluate the efficacy of BAT3306 and EU-Keytruda® and US-Keytruda® given with chemotherapy using ORR at different time points, DoR, PFS, and OS in participants with nsNSCLC
6. To evaluate immunogenicity of BAT3306 and EU-Keytruda® and US-Keytruda® and its impact on PK, efficacy, and safety in participants with nsNSCLC

Conditions and MedDRA coding

Stage IV Non-squamous non-small cell lung cancer

Study design 6 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Male or female, age ≥18 years on the day of signing informed consent.
2. Participants are able to give voluntary informed consent and understand the study and are willing to follow and complete all the test procedures.
3. Life expectancy ≥3 months per the investigator’s evaluation.
4. ECOG performance status ≤1.
5. Histologically/cytologically confirmed diagnosis of Stage IV (AJCC 8th edition) nsNSCLC.
6. Tumors without EGFR mutation/ROS1 rearrangement /ALK rearrangement
7. Have not received prior systemic treatment for their advanced/metastatic nsNSCLC. Participants who received adjuvant or neoadjuvant therapy are eligible if the adjuvant/neoadjuvant therapy was completed at least 12 months prior to the development of metastatic disease.
8. Have provided tumor tissue from locations not radiated prior to biopsy; formalin-fixed specimens after the participants have been diagnosed with metastatic disease will be preferred for determination of PD-L1 status prior to randomization. Biopsies obtained prior to receipt of adjuvant/neoadjuvant chemotherapy will be permitted if recent biopsy is not feasible.
9. Have measurable disease per RECIST v1.1. that was not in a prior radiation or other locally treated area as determined by BIRC assessment. Target lesions situated in a previously irradiated area will be considered measurable if progression has been demonstrated in such lesions.
10. Have adequate organ function as indicated by the following laboratory values: Bone marrow reserve: • Absolute neutrophil count ≥1.5 × 109/L without growth factor support in the 2 weeks prior to study drug administration • Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without growth factor support and transfusion in 2 weeks prior to study drug administration • Platelet count ≥100 × 109/L without growth factor support and transfusion in 2 weeks prior to study drug administration Hepatic function: • Total bilirubin ≤1.5 × the ULN or direct bilirubin ≤1.0×ULN for participants with total bilirubin levels>1.5×ULN. • AST and ALT ≤2.5 × ULN (or ≤5 × ULN for participants with liver metastases). Renal function: • Calculated creatinine clearance (CrCL) ≥50 mL/min (Cockroft-Gault Equation: CGGFR={[140-age (yrs.)] × weight (kg)/[72×serum creatinine (mg/dL)]} × (0.85 if female). Coagulation function: • Coagulation tests International normalized ratio (INR) or Prothrombin Time (PT) ≤1.5 × ULN, Activated Partial Thromboplastin Time (aPTT) or Partial Thromboplastin Time (PTT) ≤1.5 × ULN (INR in the range of 2-3 is acceptable on oral anticoagulants).
11. Female of childbearing potential should have a negative urine or serum pregnancy test within 7 days prior to receiving the first dose of study intervention. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
12. Female of childbearing potential must be willing to use an adequate method of contraception, for the course of the study through 120 days after the last dose of study intervention (BAT3306, EU-Keytruda®, or US-Keytruda®) and through 180 days after last dose of chemotherapeutic agents as specified in the protocol. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the participant.
13. Male participant with a female partner(s) of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study intervention through 120 days after the last dose of study intervention (BAT3306, EU-Keytruda®, or US-Keytruda®) and through 180 days after last dose of chemotherapeutic agents as specified in the protocol. Male participant with a pregnant partner must agree to use a condom; no additional method of contraception is required for the pregnant partner. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the participant.
14. Must agree to adhere to the current state and national advice regarding minimizing exposure to COVID-19 from the first Screening Visit until the EOS Visit.

Exclusion criteria 25

1. Is pregnant or a nursing female.
2. Has predominantly squamous cell histology NSCLC. If small cell element is present the participant is ineligible.
3. Is currently participating and receiving an investigational agent or has participated in a study of an investigational agent and received an investigational agent or used an investigational device within 4 weeks prior to administration of the first dose of study intervention.
4. Before the first dose of study intervention: • Had received prior systemic antineoplastic chemotherapy and targeted, biological therapy and other types of anti-tumor therapies (e.g., osimertinib, bevacizumab, cetuximab), for metastatic disease. • Had prior treatment with any other anti-PD-1, PD-L1 or PD-L2 agent or an antibody targeting other immuno-regulatory receptors or mechanisms. Examples of such antibodies include (but are not limited to) antibodies against TIGIT, IDO, PD-L1, CTLA-4, and LAG3. • Has participated in any other BAT3306 study and has been treated with BAT3306. • Had major surgery <3 weeks prior to first dose. • Received radiation therapy to the lung that is > 30 Gy within 6 months of the first dose of study intervention. • Completed palliative radiotherapy within 14 days of the first dose of study intervention.
5. Is expected to require any other form of antineoplastic therapy while participating in the study.
6. Vaccinated with any live virus vaccine within 4 weeks prior to first dose of study intervention. Seasonal flu vaccines that are categorized as inactivated or killed virus are permitted. COVID-19 vaccination: An approved COVID-19 vaccine within 2 weeks prior to the first dose of study intervention is not permitted. There can be exceptions on a case-by-case as approved by Medical Monitor.
7. Has clinically active diverticulitis, intra-abdominal abscess, gastro-intestinal obstruction, or peritoneal carcinomatosis.
8. Has known active central nervous system metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are clinically stable for at least 2 weeks prior to first dose of study intervention and have no imaging evidence of new or enlarging brain metastases in 2 weeks prior to first dose of study intervention and are off steroids at least 3 days prior to first dose of study intervention. Stable brain metastases by this definition should be established prior to the first dose of study intervention. Participants with known untreated, asymptomatic brain metastases (i.e., no neurological symptoms, no requirements for corticosteroids, no or minimal surrounding edema, and no lesion >1.5 cm) may participate but will require regular imaging of the brain as a site of disease.
9. History of a Grade 3 - 4 allergic reaction to treatment with another antibody.
10. Has active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
11. Known allergies, hypersensitivity, or intolerance to any of the study intervention or their excipients.
12. Is on chronic systemic steroids. Participants with asthma that require intermittent use of bronchodilators, inhaled steroids, or local steroid injections would not be excluded from the study.
13. Is unable or unwilling to take folic acid or vitamin B12 supplementation
14. Has an active infection requiring therapy or the participants need to receive intravenous antibiotics within two weeks prior to first dose, or they need any type of antibiotics within one week prior to first dose.
15. Human immunodeficiency virus infection, syphilis, or active tuberculosis infection at Screening. Screening for HIV, syphilis, and tuberculosis will be performed according to local practice and local regulatory guidance.
16. Active Hepatitis B or C. Only when HBV carriers without active disease (HBV DNA titer < 1000 cps/mL or 200 IU/mL) or cured Hepatitis C (negative HCV RNA test) may be enrolled.
17. Has known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study.
18. Is, at the time of signing informed consent, a known regular user of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol).
19. Has symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible.
20. Has a history of interstitial lung disease/ (non-infectious) pneumonitis that required steroids or current interstitial lung disease/(non-infectious) pneumonitis.
21. Participants with a history of tissue or organ transplantation.
22. Severe or uncontrolled cardiac disease requiring treatment, congestive heart failure (New York Heart Association) NYHA III or IV, unstable angina pectoris even if medically controlled, history of myocardial infarction during the last 6 months (at Screening), serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia).
23. Poorly controlled hypertension or resting blood pressure > 150/100 mmHg in the presence of a stable regimen of antihypertensive therapy during screening..
24. Previous malignancy other than NSCLC in the last 5 years except for basal cell cancer of the skin or pre-invasive cancer of the cervix.
25. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the Investigator.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. PK parameters
2. Confirmed best overall tumor response as assessed by BIRC according to RECIST Version 1.1 (tumor assessments after initiation of a new anti-cancer treatment are excluded)

Secondary endpoints 5

1. PK parameters Ctrough
2. Vital signs, physical examination, electrocardiogram parameters, clinical laboratory tests, adverse events
3. Immunogenicity evaluation: ADA positive rate, ADA titer, and NAb
4. ORR based on tumor response as assessed by BIRC, and confirmed best overall response by the end of study assessed according to RECIST Version 1.1 • DoR • PFS • OS by local radiologist/Investigator after
5. Relationship between ADA or NAb results and drug concentrations, tumor responses and adverse events

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 2

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bio-Thera Solutions Ltd.

Sponsor organisation

Bio-Thera Solutions Ltd.

Address

11 Kaiyuan Road, Huangpu Huangpu

City

Guangzhou

Postcode

510765

Country

China

Scientific contact point

Organisation

Bio-Thera Solutions Ltd.

Contact name

Clinical Operation Department

Public contact point

Organisation

Bio-Thera Solutions Ltd.

Contact name

Clinical Operation Department

Third parties 7

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Documents 19 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications