A Phase 1/2, open-label, multi-center study of the safety and efficacy ofKY1044 as single agent and in combination with anti-PD-L1 (atezolizumab) in adult patients with selected advanced malignancies
- Conditions
- Advanced/metastatic malignancies, and preferred indications: head and neck squamous cell carcinoma (HNSCC), non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), esophageal cancer, gastric cancer, melanoma, renal cell cancer, pancreatic cancer, cervical cancer, and triple negative breast cancer (BC)MedDRA version: 21.0Level: LLTClassification code 10015362Term: Esophageal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: PTClassification code 10063916Term: Metastatic gastric cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: LLTClassification code 10008229Term: Cervical cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10075566Term: Triple negative breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: LLTClassification code 10077738Term: Hepatocellular carcinoma metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0Level: PTClassification code 10033609Term: Pancreatic carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0Level: PTClassification code 10038389Term: Renal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: PTClassification code 10025650Term: Malignant melanomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: PTClassification code 10017758Term: Gastric cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant
- Registration Number
- EUCTR2018-003172-12-PL
- Lead Sponsor
- Kymab Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 412
1. Written informed consent must be obtained prior to any procedures
2. Age =18 years (=20 years in Taiwan)
3. Histologically documented advanced/metastatic malignancies
4. Phase 1 and Phase 2 patients with advanced/metastatic malignancies who have measurable disease (non-measurable disease is allowed only in Phase 1) as determined by RECIST 1.1 (refer to Appendix 2) will be eligible if, according to the 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:
a. Phase 1 (including enrichment part):
Patients with advanced/metastatic malignancies, and preferred indications as identified in Section 3.1 (NSCLC, HNSCC, HCC, melanoma, cervical, gastric/esophageal, renal, pancreatic, and triple negative BC)
b. Phase 2 KY1044 single agent:
Patients with advanced/metastatic malignancies in indications in which signs of anti tumor activity (CR, PR or durable SD with tumor shrinkage that does not qualify for PR) were seen during the dose escalation of KY1044 as single agent.
c. Phase 2 KY1044 in combination with atezolizumab:
Patients with advanced/metastatic malignancies in the below selected indications, and/or indications which have shown promising activity in Phase 1:
• NSCLC (anti PD (L)1 therapy naïve and pre treated between 1 and 2 prior lines of systemic therapy for advanced disease)
• Gastric/Esophageal (anti PD (L)1 therapy naïve and pre treated)
• Recurrent and/or metastatic HNSCC (anti PD (L)1 therapy naïve and pre treated between 1 and 2 prior lines of systemic therapy for
advanced disease)
• 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
5. 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
6. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
7. Life expectancy longer than 12 weeks
8. Must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy according to the treating institution’s guidelines. Patient must be willing to undergo a new tumor biopsy at screening, and during therapy on the study
9. Females of child bearing potential must be using two highly effective
contraceptive measures for the duration of study participation and for at least 5 months after discontinuing study treatment, or longer if the half-life of KY1044 is observed to exceed that of atezolizumab (see Section 5.8).Females must not be breast feeding and must have a negative pregnancy test prior to start of dosing or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:
- Post-menopausal defined as aged =50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments
- Women less than 50 years old would be considered postmenopausal if they have been amenorrhoeic for at least 12 months following the cessation of exogenous hormonal treatments, and have serum follicle-stimulating hormone and luteinizing hormone levels in the postmenopausal range for the institution
- Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
10. For the d
1. Presence of symptomatic 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. Patients with treated brain metastasis unless neurologically stable (for 4 weeks post-treatment and prior to study enrolment) and off of steroids for at least 2 weeks before the first dose of study treatment
2. History of severe hypersensitivity to other mAbs and/or their excipients
3. Known presence of neutralizing anti-atezolizumab antibodies (for patients previously treated with atezolizumab)
4. Having out of range laboratory values (creatinine, bilirubin, ALT, AST, Absolute neutrophil count , Platelet count, Hemoglobin)
5. Impaired cardiac function or clinically significant cardiac disease, including any of the following:
- Clinically significant and/or uncontrolled heart disease (congestive heart failure requiring treatment, uncontrolled hypertension or clinically significant arrhythmia)
- QTcF >470 msec on screening ECG using Fridericia's formula (QTcF) or congenital long QT syndrome
- Acute myocardial infarction or unstable angina pectoris <3 months prior to first dose of study treatment
6. Known human immunodeficiency virus, active hepatitis B virus or active hepatitis C virus infection. Patients with any severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection.
7. Malignant disease, other than that being treated in this study.
8. Any medical condition that would, in the Investigator’s judgment, prevent the patient’s participation in the clinical study due to safety concerns, compliance with clinical study procedures or interpretation of study results
9. Active autoimmune disease or a documented history of autoimmune disease
10. Patients 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
11. Patients with a history of drug-induced pneumonitis or current pneumonitis
12. Systemic steroid therapy or any immunosuppressive therapy. Topical, inhaled, nasal, and ophthalmic steroids are not prohibited
13. Herbal preparations/medications (including, but not limited to: St. John’s Wort, kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone, yohimbe, saw palmetto, and ginseng) are prohibited from the time that patients enter the screening period (at least 7 days prior to first dose of study treatment) until the last dose of study treatment (3 weeks for St John’s Wort)
14. Warfarin and other types of long acting anticoagulants (such as phenprocumon and or anti Xa inhibitors with a half life of >12 hours) is prohibited within 4 weeks of the first dose of study treatment and patients requiring anticoagulant treatment should switch to low molecular weight heparin or anti Xa inhibitors with a half life of =12 hours
15. Use of live or live attenuated vaccines against infectious diseases within 4 weeks of the first dose of study treatment. SARS-CoV-2 vaccines are allowed (unless it is live or live attenuated) at least 7 days prior to the first dose.
16. Systemic anti-cancer therapy within 2 weeks of the first dose of study treatment. For cytotoxic agents that have major delayed toxicity, 4 weeks is indicated as washout period
17. Major surgery within 2 weeks of the first dose of study treatment
18. Anti-CTLA4, anti-PD-(L)1 treatment with
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method