A Phase 1/2, open label, multi-center study to evaluate the safety, efficacy and tolerability
of KY1044 as single agent and in combination with anti-PD-L1 (atezolizumab) in adult patients
with selected advanced malignancies, who are ineligible for or there are no available
therapies known to confer a clinical benefit for their disease, or they have exhausted all
such available options in each indication and therefore will be patients for whom a clinical
trial is appropriate.
Inclusion Criteria:
- Age ≥18 years (≥20 years in Taiwan)
- Histologically documented advanced/metastatic malignancies
- Phase 1 and Phase 2 participants with advanced/metastatic malignancies who have
measurable disease (non-measurable disease is allowed only in Phase 1) as determined
by RECIST 1.1 will be eligible if, according to the National Comprehensive Cancer
Network (NCCN) guidelines, there are no available therapies known to confer a clinical
benefit for their disease, or they have exhausted all such available options.
Additionally, the following specific tumor indications will be enrolled:
1. Phase 1: Participants with advanced/metastatic malignancies, and preferred
indications (non-small cell lung cancer (NSCLC), head and neck squamous cell
carcinoma (HNSCC), hepatocellular carcinoma (HCC), melanoma, cervical,
esophageal, gastric, renal, pancreatic, and triple negative breast cancer)
2. Phase 2 KY1044 single agent: Participants with advanced/metastatic malignancies
in indications in which signs of anti-tumor activity (Complete Response (CR),
Partial Response (PR) or durable stable disease (SD) with tumor shrinkage that
does not qualify for PR) were seen during the dose escalation of KY1044 as single
agent
3. Phase 2 KY1044 in combination with atezolizumab: Participants with
advanced/metastatic malignancies in the selected indications below, and/or
indications which have shown promising activity in Phase 1:
- NSCLC (anti-PD-(L)1 therapy naïve and pre-treated)
- Gastric (anti-PD-(L)1 therapy naïve and pre-treated)
- HNSCC (anti-PD-(L)1 therapy naïve and pre-treated)
- Esophageal (anti-PD-(L)1 therapy naïve and pre-treated)
- Cervical (anti-PD-(L)1 therapy naïve and pre-treated)
- Indications, in which signs of anti-tumor activity has been observed in
Phase 1 with KY1044 in combination with atezolizumab
- Prior therapy with anti-PD-(L)1 inhibitors is allowed provided any toxicity attributed
to prior anti-PD-(L)1-directed therapy did not lead to discontinuation of therapy
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
- Life expectancy longer than 12 weeks
- Must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy
according to the treating institution's guidelines. Participants must be willing to
undergo a new tumor biopsy at screening, and during therapy on the study
Exclusion Criteria:
- Presence of symptomatic central nervous system (CNS) metastases, or CNS metastases
that require local CNS-directed therapy, or increasing doses of corticosteroids within
the prior 2 weeks of first dose of study treatment
- History of severe hypersensitivity reactions to other monoclonal antibodies and/or
their excipients
- Known presence of neutralizing anti-atezolizumab antibodies (for patients previously
treated with atezolizumab)
- Having out of range laboratory values: creatinine, bilirubin, alanine aminotransferase
(ALT), aspartate aminotransferase (AST), absolute neutrophil count (ANC), platelet
count, hemoglobin
- Impaired cardiac function or clinically significant cardiac disease
- Known human immunodeficiency virus (HIV), active hepatitis B virus (HBV) or active
hepatitis C virus (HCV) infection
- Malignant disease, other than that being treated in this study
- Any medical condition that would, in the Investigator's judgment, prevent
participation in the clinical study due to safety concerns, compliance with clinical
study procedures or interpretation of study results
- Active autoimmune disease or a documented history of autoimmune disease
- Participants previously exposed to anti-PD-(L)1 treatment who are not adequately
treated for skin rash or had no replacement therapy for endocrinopathies should be
excluded
- Participants with a history of drug-induced pneumonitis or current pneumonitis
- Systemic steroid therapy or any immunosuppressive therapy. Topical, inhaled, nasal,
and ophthalmic steroids are not prohibited
- Use of live attenuated vaccines against infectious diseases within 4 weeks of the
first dose of study treatment. SARS-CoV-2 vaccines authorized for use by the competent
local regulatory health authorities for active immunization to prevent COVID 19 are
allowed (unless the vaccine is live or live attenuated) and must be given in
accordance with the prevailing immunization guidelines.
- Anti-CTLA4, anti-PD-(L)1 treatment within 4 weeks of the first dose of study treatment
- Pre-treatment with anti-CTLA4 antibodies in combination with any other antibody or
drug specifically targeting T-cell co-stimulation or checkpoint pathway
- Presence of Common Terminology Criteria for Adverse Events version 5 (CTCAE v5) ≥Grade
2 toxicity (except alopecia, peripheral neuropathy and ototoxicity, which are excluded
if CTCAE v5 ≥Grade 3) due to prior cancer therapy
- Radiotherapy within 2 weeks of the first dose of study treatment, except for
palliative radiotherapy to a limited field, such as for the treatment of bone pain or
a focally painful tumor mass. To allow evaluation for response to treatment,
participants enrolled in the Phase 2 part must have remaining measurable disease that
has not been irradiated
- Pregnant or lactating women
