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Advanced or Metastatic Solid TumorsPhase 1NCT03248843

A Study of PD-L1 Antibody KN035 in Japanese Subjects With Locally Advanced or Metastatic Solid Tumors

A Phase 1 study testing KN035 in people with Advanced or Metastatic Solid Tumors, run by 3D Medicines (Sichuan) Co., Ltd. at 2 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is an open label, dose escalation study to evaluate the safety and tolerability of KN035 in Japanese patients with advanced and metastatic solid tumor. The dose escalation will follow the widely used 3+3 design. Read more about this study

Who is it for?
Ages 20 years and older
Conditions the study is for
Advanced or Metastatic Solid Tumors
What is being tested?
KN035
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
2 sitesJapan
Study dates
15 Sep 2017to 31 Mar 2020
Phase
Phase 1
Are there results?
None posted in the registry

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 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subjects must have a histological or cytological diagnosis of any type of carcinoma, progressive metastatic disease, or progressive locally advanced disease not amenable to local therapy. Subjects must have no standard anti-cancer therapy option, who failed established standard medical anti-cancer therapies for a given tumor type.
  • Subject is male or female and ≥ 18 years of age on the day of signing informed consent. However, in case a subject is younger than 20 years old, written informed consent will be obtained from both a subject and a legal representative.
  • Subject must have a performance status of 0 to 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
  • Subject must have adequate hematologic and organ function.
  • Subject has voluntarily agreed to participate by giving written informed consent.
  • Women able to get pregnant has a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. The serum pregnancy test must be negative for the subject to be eligible.
  • Female subjects enrolled in the study must be willing to use either 2 adequate barrier methods or a barrier method plus a hormonal method of contraception to prevent pregnancy or to abstain from heterosexual activity throughout the study, starting with Informed Consent through 120 days after the last dose of study therapy. Women who have had a surgical hysterectomy and/or bilateral oophorectomy, or who are postmenopausal and have not had a menstrual cycle for 12 consecutive months without medical/medicinal reasons are not considered to be of childbearing potential. Approved contraceptive methods include for example; intra uterine device, diaphragm with spermicide*, cervical cap* with spermicide*, male condoms, or female condom *with spermicide* and hormonal method of contraception. Spermicides alone are not an acceptable method of contraception. *: not approved/certified in Japan.
  • Male subjects must agree to use an adequate method of contraception starting with Informed Consent through 120 days after the last dose of study therapy.

Who cannot join

  • Subject who not recovered from the effects of any prior chemotherapy, radioactive, or biological cancer therapy prior to the first dose of study therapy (for prior cancer therapy drugs, a washout of 5 half-lives or 28 days whichever is shorter is required), or who has not recovered to CTCAE Grade 1 or better from the adverse events due to cancer therapeutics administered more than 4 weeks earlier. Subject who has had erlotinib, gefitinib, afatinib, or crizotinib within 1 week prior to the first dose of study therapy, or who has not recovered to CTCAE Grade 1 or better from the adverse events due to any of these drugs administered more than 1 week earlier. Grade 2 alopecia is allowed to enter.
  • Subject is expected to require any other form of antineoplastic therapy while on study (including maintenance therapy with another agent for NSCLC).
  • Subject had prior treatment targeting PD-L1. Subjects with prior treatment targeting PD-1 are allowed to enroll if the subject has a washout time of at least 4 weeks. Examples of such anti-PD-L1 agents include (but are not limited to): BMS-936559 (MDX 1105); MPDL3280A (RG7446); and MEDI4736.
  • Subject has a medical condition that requires chronic systemic steroid therapy or requires any other form of immunosuppressive medication. However, subjects using physiologic replacement doses of hydrocortisone, or its equivalent, will be considered eligible for this study: up to 20 mg of hydrocortisone (or 5 mg of prednisone) in the morning and 10 mg of hydrocortisone (or 2.5 mg of prednisone) in the evening. Topical, intraocular, and intranasal steroids are allowed.
  • Subject has risk factors for bowel obstruction or bowel perforation (examples include but not limited to a history of acute diverticulitis, intra-abdominal abscess, or abdominal carcinomatosis).
  • Subject has a known history of a hematologic malignancy, malignant primary brain tumor or malignant sarcoma, or of another malignant primary solid tumor, unless the subject has undergone potentially curative therapy with no evidence of that disease for 5 years.
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  • Subject has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are clinically stable for at least 4 weeks prior to study entry, have no evidence of new or enlarging brain metastases and are off steroids for at least 7 days from first dose of KN035.
  • Subject previously had a severe hypersensitivity reaction to treatment with another mAb.
  • Subject has a history of pneumonitis or interstitial lung disease irrespective of causes (For the purpose of screening of interstitial lung disease, chest X-ray, Sialylated carbohydrate antigen (KL-6) (hereafter, KL-6), percutaneous arterial blood oxygen saturation (hereafter, SpO2) and auscultation are conducted).
  • Subject has an active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism that is stable on hormone replacement will not be excluded from the study.
  • Subject has an active infection requiring therapy.
  • Subject is positive for Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies), active hepatitis B (HBsAg reactive) or hepatitis C (HCV RNA (qualitative) is detected); subjects with negative hepatitis C antibody testing may not need RNA testing.
  • Subject has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator.
  • Subject has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Subject has a marked baseline prolongation of QT/QTc (Fridericia's formula) interval (e.g., repeated demonstration of a QTc interval >450 milliseconds (ms) as a guidance considering the patient's background of physiological conditions), or a history of additional risk factors for torsade de pointes (TdP, e.g., heart failure, hypokalemia, family history of Long QT Syndrome), or is using concomitant medications that prolong the QT/QTc interval.
  • Subject is, at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol).
  • Subjects with symptomatic ascites or pleural effusion. A subject who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible.
  • Subject is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study. However, breastfeeding female subject who stopped breastfeeding can be included only if she agrees to stop breastfeeding during the treatment of the investigational drug and to restart breastfeeding 120 days after the last dose of the investigational drug.

Trial locations and contacts

2 sites in 1 country.

Japan2 sites

  • St. Marianna University School of Medicine Hospital

    Kawasaki, 216-8511

  • National Cancer Center Hospital

    Tokyo, 104-0045

Other trials in Japan

About this study

Official title: A Phase I, Open Label, Dose Escalation Study of The Safety and Pharmacokinetics of Anti-PD-L1 Monoclonal Antibody KN035 Administered in Subcutaneous Injection as A Single Agent to Japanese Subjects With Locally Advanced or Metastatic Solid Tumors

This is an open label, dose escalation study to evaluate the safety and tolerability of KN035 in Japanese patients with advanced and metastatic solid tumor. The dose escalation will follow the widely used 3+3 design.

Read the detailed description

This is an open label, dose escalation study to evaluate the safety and tolerability of KN035 in Japanese patients with advanced and metastatic solid tumor.

The dose escalation will follow the widely used 3+3 design. Cohorts of 3-6 subjects will be enrolled sequentially at escalating doses of 1.0, 2.5, 5.0 and 10 mg/kg weekly. Dose escalation will continue until identification of MTD up to a maximum dose of 10 mg/kg. MTD is defined as the highest dose studied at which no more than 1 of 6 subjects has experienced a dose-limiting toxicity (DLT) in Cycle 1. The enrolled patients are managed under hospitalization for DLT observation period (C1 28 days). If no DLTs occur in a cohort of 3 subjects, a new cohort of 3 subjects will be treated at the next higher dose level. If 1 of 3 subjects in a cohort experiences a DLT, that cohort will be expanded to 6 subjects. If only 1 of the 6 subjects has a DLT, then the next cohort of 3 subjects will be treated at the next higher dose level. If 2 or more DLTs occur within a cohort, then that dose level will be above the MTD, and the previous lower (tolerated) dose level will be considered the MTD if ≤ 1 in 6 subjects has a DLT.

A subject who withdraws from the study during Cycle 1 for reasons other than a DLT will be replaced.

Subjects will be monitored for safety and efficacy throughout the study. After radiological tumor assessment at Screening, the first radiological assessment of tumor response status will be performed at Week 12 (± 1 week), unless there is clinical indication warranting earlier radiologic imaging. The same imaging technique used at baseline has to be used throughout the study.

Being tested
KN035
Keywords
KN035, Solid tumors, Phase 1

What participants receive

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

  • KN035Drug

    Four cohorts dosed at 1.0 mg/kg, 2.5 mg/kg, 5.0 mg/kg, and 10 mg/kg weekly. All cohorts are administered by subcutaneous injection (SC).

Study groups in NCT03248843
Study groupRoleWhat they receive
KN035ExperimentalCohorts of 3-6 subjects will be enrolled sequentially at escalating doses of 1.0, 2.5, 5.0 and 10 mg/kg weekly. Dose escalation will continue until identification of MTD up to a maximum dose of 10 mg/kg.
Receives: Drug: KN035

What is being measured

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

  1. Incidence of dose limiting toxicities

    Measured: From screening to up to cycle 1 (28 days)

  2. KN035 safety and tolerability assessed by monitoring AEs per the NCI-CTC-AE Version 4.03, physical examination, electrocardiograms, laboratory measurements and severity of adverse events

    The safety of KN035 will be assessed throughout the study by monitoring adverse events (AEs) per the NCI-CTC-AE Version 4.03, physical examination, electrocardiograms, laboratory measurements and severity of adverse events.

    Measured: From screening to up to 1 months after the last dose of study drug (up to approximately 2 years

Secondary outcomes (15)

  1. Peak Plasma Concentration (Cmax) of KN035 in Japanese patients

    Measured: From Pre-dose of the first dose to up to 48 weeks

  2. Peak Time (Tmax) of KN035 in Japanese patients

    Measured: From Pre-dose of the first dose to up to 48 weeks

  3. Area under the plasma concentration versus time curve (AUC) of KN035 in Japanese patients

    Measured: From Pre-dose of the first dose to up to 48 weeks

  4. t1/2 of KN035 in Japanese patients

    Measured: From Pre-dose of the first dose to up to 48 weeks

  5. Trough concentration of KN035 in Japanese patients

    Measured: From Pre-dose of the first dose to up to 48 weeks

  6. Plasma clearance (CL) of KN035 in Japanese patients

    Measured: From Pre-dose of the first dose to up to 48 weeks

  7. Apparent volume of distribution of KN035 in Japanese patients

    Measured: From Pre-dose of the first dose to up to 48 weeks

  8. Accumulation rate of KN035 in Japanese patients

    Measured: From Pre-dose of the first dose to up to 48 weeks

  9. Anti-Drug Antibody of KN035 in Japanese patients

    Measured: From Pre-dose of the first dose to up to 48 weeks

  10. Changes of lymphocyte Subtyping

    Measured: From Pre-dose of the first dose to up to 48 weeks

  11. Changes of cytokine

    Measured: From Pre-dose of the first dose to up to 6 months

  12. Objective Response Rate (ORR)

    Measured: Up to 2 approximately years

  13. Disease Control Rate (DCR)

    Measured: Up to 2 approximately years

  14. Progression-Free survival (PFS)

    Measured: Up to 2 approximately years

  15. Duration of Response (DOR)

    Measured: Up to 2 approximately years

Timeline

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

  1. First posted14 Aug 2017
  2. Study start15 Sep 2017
  3. Primary completion31 Mar 2020
  4. Study completion31 Mar 2020

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Cohorts of 3-6 subjects will be enrolled sequentially at escalating doses of 1.0, 2.5, 5.0 and 10 mg/kg of KN035 weekly.
Masking
None (open label)
Enrolment
35 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03248843
Sponsor's protocol ID
KN035-JP-001
Status last verified
Feb 2022
First submitted
7 Aug 2017
Last updated
8 Feb 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Cui C, Wang J, Wang C, Xu T, Qin L, Xiao S, Gong J, Song L, Liu D. Model-informed drug development of envafolimab, a subcutaneously injectable PD-L1 antibody, in patients with advanced solid tumors. Oncologist. 2024 Sep 6;29(9):e1189-e1200. doi: 10.1093/oncolo/oyae102.

    PubMed 38982653

  • Shimizu T, Nakajima TE, Yamamoto N, Yonemori K, Koyama T, Kondo S, Sunakawa Y, Izawa N, Horie Y, Xiang S, Xu S, Qin L, Gong J, Liu D. Phase I study of envafolimab (KN035), a novel subcutaneous single-domain anti-PD-L1 monoclonal antibody, in Japanese patients with advanced solid tumors. Invest New Drugs. 2022 Oct;40(5):1021-1031. doi: 10.1007/s10637-022-01287-7. Epub 2022 Aug 6.

    PubMed 35932387

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing KN035 in people with Advanced or Metastatic Solid Tumors, run by 3D Medicines (Sichuan) Co., Ltd. at 2 sites in Japan.

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 8 inclusion and 18 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: finished, as of the sponsor's last update on 8 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Japan. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Incidence of dose limiting toxicities (time frame: From screening to up to cycle 1 (28 days)). The study lists 2 primary outcomes in all. 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 NCT03248843, which also lists 2 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 8 Feb 2022.

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