Phase 1 Study of Anti-PD-L1 Monoclonal Antibody KN035 to Treat Locally Advanced or Metastatic Solid Tumors

• Register: ClinicalTrials.gov
• Last refreshed on: 14 June 2021
• Main ID: NCT02827968
• Date of registration: 29/06/2016
• Prospective Registration: Yes
• Primary sponsor: 3D Medicines (Sichuan) Co., Ltd.
• Public title: Phase 1 Study of Anti-PD-L1 Monoclonal Antibody KN035 to Treat Locally Advanced or Metastatic Solid Tumors
• Scientific 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 Subjects With Locally Advanced or Metastatic Solid Tumors
• Date of first enrolment: January 13, 2017
• Target sample size: 28
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02827968
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: David Liu, M.D.
• Affiliation: 3D Medicines

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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 failed established standard medical anti-cancer
therapies for a given tumor type or have been intolerant to such therapy, or in the
opinion of the Investigator have been considered ineligible for a particular form of
standard therapy on medical grounds.

- Subject is male or female and = 18 years of age on day of signing informed consent.

- Subject must have a performance status of 0 or 1 on the Eastern Cooperative Oncology
Group (ECOG) Performance Scale.

- Subject must have adequate hematologic and organ function. Note: If subject is
receiving anticoagulants, then value must be within therapeutic range for the
condition the subject is being treated for.

- Subject has voluntarily agreed to participate by giving written informed consent. If
subject has agreed to a newly obtained biopsy of tumor (that can be biopsied based on
Investigator's assessment). Tissue obtained for the biopsy must not be previously
irradiated. No systemic antineoplastic therapy may be received by the subject between
the time of the biopsy and the first administration of KN035.

- Female subject of childbearing potential 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, who are not free from menses for > 2 years,
post hysterectomy/oophorectomy, or surgically sterilized, 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 Visit 1 through 120 days after the last dose of study
therapy. Approved contraceptive methods include for example; intra uterine device,
diaphragm with spermicide, cervical cap with spermicide, male condoms, or female
condom with spermicide. Spermicides alone are not an acceptable method of
contraception.

Male subjects must agree to use an adequate method of contraception starting with the first
dose of study drug through 120 days after the last dose of study therapy.

Exclusion Criteria:

- 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 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.

- 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 axis or CTLA 4. 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 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 hydrocortisone (or 5 mg of prednisone) in the
morning and 10 mg hydrocortisone (or 2.5 mg of prednisone) in the evening.

- 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.

Note: The time requirement does not apply to subjects who underwent successful definitive
resection of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell
carcinoma of the skin, in situ cervical cancer, or other in situ cancers.

- 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.

- 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


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Solid Tumors

Intervention(s)

Drug: KN035

Primary Outcome(s)

Incidence of dose limiting toxicities (DLTs) [Time Frame: From screening to up to cycle 1 (28 days)]

Percentage of participants with adverse events (AEs), serious adverse events and AEs of special interest [Time Frame: From screening to up to 3 months after the last dose of study drug (up to approximately 2 years)]

Secondary Outcome(s)

Percentage of Participants with Objective Response as determined by RECIST v1.1 [Time Frame: Baseline until disease progression, death, loss to follow-up, initiation of another anti-cancer treatment, withdrawal of consent, or study termination by the Sponsor, whichever occurs first (up to approximately 2 years)]

Percentage of Participants with Best Overall Response as determined by Response Evaluation Criteria in Solid Tumours (RECIST) Version (v) 1.1 [Time Frame: Baseline until disease progression, death, loss to follow-up, initiation of another anti-cancer treatment, withdrawal of consent, or study termination by the Sponsor, whichever occurs first (up to approximately 2 years)]

Duration of Objective Response as determined by RECIST v1.1 [Time Frame: Baseline until disease progression, death, loss to follow-up, initiation of another anti-cancer treatment, withdrawal of consent, or study termination by the Sponsor, whichever occurs first (up to approximately 2 years)]

Percentage of participants with anti-therapeutic antibody (ATA) [Time Frame: From screening to up to 3 months after the last dose of study drug (up to approximately 2 years)]

Progression Free Survival Duration as determined by RECIST v1.1 [Time Frame: Baseline until disease progression, death, loss to follow-up, initiation of another anti-cancer treatment, withdrawal of consent, or study termination by the Sponsor, whichever occurs first (up to approximately 2 years)]

Overall Survival Duration [Time Frame: Baseline until disease progression, death, loss to follow-up, initiation of another anti-cancer treatment, withdrawal of consent, or study termination by the Sponsor, whichever occurs first (up to approximately 2 years)]

Serum Concentrations of KN035 [Time Frame: From Pre-dose of the first dose to up to 3 months after the last dose of study drug (up to approximately 2 years)]

Secondary ID(s)

KN035-US-001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors