Clinical Trials List
Protocol NumberKY1044-CT01
NCT Number(ClinicalTrials.gov Identfier)NCT03829501
Completed
2019-01-01 - 2023-09-30
Phase I
Not yet recruiting4
Recruiting2
Terminated1
A Phase 1/2, open-label, multi-center study of the safety and efficacy of KY1044 as single agent and in combination with anti-PD-L1 (atezolizumab) in adult patients with selected advanced malignancies
-
Trial Applicant
Pharmaceutical Research Associates Taiwan Inc.
-
Sponsor
Kymab Limited
-
Trial scale
Multi-Regional Multi-Center
-
Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- James Chih-Hsin Yang Division of Hematology & Oncology
- Jih-Hsiang Lee Division of Hematology & Oncology
- 廖斌志 Division of Hematology & Oncology
- 廖唯昱 Division of General Internal Medicine
- 張端瑩 Division of Hematology & Oncology
- Ying-Chun Shen 無
- Chong-Jen Yu Division of General Internal Medicine
- JIN-YUAN SHIH Division of General Internal Medicine
- Wei-Wu Chen Division of Hematology & Oncology
- 徐偉勛 Division of Hematology & Oncology
- 林季宏 Division of Hematology & Oncology
- TSUNG-HAO LIU 無
- Chih-Hung Hsu Division of Hematology & Oncology
- Wen-Fang Cheng Division of Obstetrics & Gynecology
- CHAO-CHI HO CHAO-CHI HO Division of General Internal Medicine
- TA-CHEN HUANG Division of Hematology & Oncology
- 陳怡君 Division of Hematology & Oncology
- YEN-SHEN LU Division of Hematology & Oncology
- JHE-CYUAN GUO Division of Hematology & Oncology
- 蔡子修 Division of General Internal Medicine
- 許嘉林 Division of General Internal Medicine
- 呂理駿 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- Su-Peng Yeh 無
- Che-Hung Lin 無
- Ming-Yu Lien 無
- Chi-Ching Chen 無
- Li-Yuan Bai 無
- Yu-Min Liao 無
- 王秀慈 無
- Chang-Fang Chiu 無
- Chen-Yuan Lin 無
- 鄭富銘 無
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- 鄭皓升醫師 無
- 石宇軒醫師 無
- 陳建志醫師 無
- Cheng-Kuang Yang 無
- Chih-Chiang Hung 無
- 謝合原醫師 無
- ZHENG-WEI ZHOU 無
- 李權醫師 無
- CHENG-HSIEN LIN 無
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- 吳敬炫醫師 Division of Hematology & Oncology
- Ta-Chih Liu Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- 吳敬炫醫師 無
- Ta-Chih Liu 無
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
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 breastcancer (BC)
Objectives
Primary objectives
-Phase 1: to characterize the safety and tolerability of KY1044 as single agent and in combination with atezolizumab and to identify recommended doses for future studies.
-Phase 2: to estimate the anti-tumor efficacy of KY1044 as single agent and in combination with atezolizumab
Test Drug
KY1044
Active Ingredient
KY1044
Dosage Form
Injection
Dosage
50mg/mL
Endpoints
主要評估指標
第 1 期：
□ 安全性：AE 和 SAE 的發生率和嚴重度，包括實驗室參數、生命徵象和 ECG 的變化
□ 耐受性：劑量中斷、調降和劑量強度
□ 治療的首 21 天當中，使用 KY1044 做為單一藥劑的劑量限制性毒性 (Dose Limiting Toxicity，DLT) 發生率
□ 治療的首 21 天當中，使用 KY1044 併用 Atezolizumab 的 DLT 發生率
第 2 期：
□ 依據 RECIST 1.1 評估的整體療效反應率 (overall response rate，ORR)
第 1 期：
□ 安全性：AE 和 SAE 的發生率和嚴重度，包括實驗室參數、生命徵象和 ECG 的變化
□ 耐受性：劑量中斷、調降和劑量強度
□ 治療的首 21 天當中，使用 KY1044 做為單一藥劑的劑量限制性毒性 (Dose Limiting Toxicity，DLT) 發生率
□ 治療的首 21 天當中，使用 KY1044 併用 Atezolizumab 的 DLT 發生率
第 2 期：
□ 依據 RECIST 1.1 評估的整體療效反應率 (overall response rate，ORR)
Inclution Criteria
1. Histologically documented advanced/metastatic malignancies
2. 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 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 (NSCLC, HNSCC, HCC, melanoma, cervical, esophageal, gastric,
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 selected
indications below, and/or indications which have shown promising
activity in Phase 1:
• NSCLC (anti-PD-(L)1 therapy naïve and pre-treated)
• HNSCC (anti-PD-(L)1 therapy naïve and pre-treated)
• Gastric (anti-PD-(L)1 therapy naïve and pre-treated)
• Esophageal cancer (anti-PD-(L)1 therapy naïve and pre-treated)
• Cervical cancer (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
3. Prior therapy with anti-PD-(L)1 inhibitors is allowed provided any
toxicity attributed to prior anti-PD-(L)1-directed therapy did notlead to
discontinuationoftherapy.
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
5. Life expectancy longer than 12 weeks
6. Musthaveasiteofdiseaseamendabletobiopsy,andbecandidatefor
tumor biopsy, according to the treating institution’s guidelines.
Patients must be willing to undergo a new tumor biopsy at screening
and during therapy onthe study
7. Women of child-bearing potential and men must agree to use adequate
contraception(hormonalorbarriermethodofbirthcontrol;abstinence)
prior to study entry and for the duration of study participation
2. 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 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 (NSCLC, HNSCC, HCC, melanoma, cervical, esophageal, gastric,
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 selected
indications below, and/or indications which have shown promising
activity in Phase 1:
• NSCLC (anti-PD-(L)1 therapy naïve and pre-treated)
• HNSCC (anti-PD-(L)1 therapy naïve and pre-treated)
• Gastric (anti-PD-(L)1 therapy naïve and pre-treated)
• Esophageal cancer (anti-PD-(L)1 therapy naïve and pre-treated)
• Cervical cancer (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
3. Prior therapy with anti-PD-(L)1 inhibitors is allowed provided any
toxicity attributed to prior anti-PD-(L)1-directed therapy did notlead to
discontinuationoftherapy.
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
5. Life expectancy longer than 12 weeks
6. Musthaveasiteofdiseaseamendabletobiopsy,andbecandidatefor
tumor biopsy, according to the treating institution’s guidelines.
Patients must be willing to undergo a new tumor biopsy at screening
and during therapy onthe study
7. Women of child-bearing potential and men must agree to use adequate
contraception(hormonalorbarriermethodofbirthcontrol;abstinence)
prior to study entry and for the duration of study participation
Exclusion Criteria
1. Presence of symptomatic central nervous system (CNS) metastases unless
neurologicallystable(for4weeks) andoffsteroids foratleast2weeks
before the first dose of study treatment.
2. History of severe hypersensitivity reactions to other monoclonal
antibodies (mAbs) and/or their excipients.
3. Known presence ofneutralizing anti-atezolizumab antibodies
4. Patients previously exposed to anti-PD-(L)1 treatment who are not
adequately treated for skin rash or have no replacement therapy for
endocrinopathies
5. Known human immunodeficiency virus (HIV), active hepatitis B virus
(HBV) or active hepatitis C virus (HCV) infection. Patients with HCC,
whoseHBVorHCVinfectioniscontrolledbyantiviraltherapy,shouldnot
be excluded.
6. Active autoimmune disease or a documented history of autoimmune
disease, including ulcerative colitis and Crohn’s disease or any condition
that requires systemic steroids.
7. Malignant disease, other than that being treated in this study. Exceptions
to this exclusion criterion include malignancies that were treated
curatively and have not recurred within 2 years prior to the first dose of
study treatment; completely resected basal cell and squamous cell skin
cancers; and completely resected carcinoma in situ of any type.
8. Systemic steroidtherapyor anyimmunosuppressive therapy (≥10mg/day
prednisone or equivalent).
9. Anti-CTLA4, anti-PD-(L)1 treatment within 4 weeks of the first dose of
study treatment
10. Pretreatment with anti-CTLA4 antibodies in combination with other
antibodies or drugs, specifically targeting T-cell stimulation or checkpoint
pathways.
11. Systemicanti-cancertherapy(tyrosinekinaseinhibitor(TKI)and/or
chemotherapy) within 2 weeks of the first dose of study treatment. For
cytotoxicagentsthathavemajordelayedtoxicity,e.g.mitomycinCand
nitrosourea, 4 weeks is indicated as washout period.
12. Use of life attenuated vaccines against infectious diseases (e.g.measles
mumps rubella (MMR combined vaccines), Rotavirus, Chickenpox,
yellow fever ) within 4 weeks of initiation of study treatment.
13. Participation in an interventional, investigational study within 4 weeks of
the first dose of study treatment.
14. Impaired cardiac function or clinically significant cardiac disease,
includinganyofthefollowing:
a. Clinically significant and/or uncontrolled heart disease such as
congestive heart failure requiring treatment (New York Heart
Association (NYHA) Grade ≥2), uncontrolled hypertension or
clinically significant arrhythmia
b. QTcF >470 msec on screening electrocardiogram (ECG) or
congenital long QT syndrome
c. Acute myocardial infarction or unstable angina pectoris <3 months
prior to first dose of study treatment
15. PresenceofCommonTerminologyCriteria forAdverseEventsVersion5
(CTCAE v5) ≥Grade 2 toxicity (except alopecia, peripheral neuropathy and
ototoxicity,whichareexcludedifCTCAEv5≥Grade3)duetopriorcancer
therapy.
16. Radiotherapy within 2 weeks of the first dose of study treatment, exceptfor
palliative radiotherapy to a limited field, such as for the treatment of bone
pain or a focally painfultumor mass.To allowevaluation for response to
treatment, patients enrolled in the Phase 2 part must have remaining
measurablediseasethathasnotbeenirradiated.
neurologicallystable(for4weeks) andoffsteroids foratleast2weeks
before the first dose of study treatment.
2. History of severe hypersensitivity reactions to other monoclonal
antibodies (mAbs) and/or their excipients.
3. Known presence ofneutralizing anti-atezolizumab antibodies
4. Patients previously exposed to anti-PD-(L)1 treatment who are not
adequately treated for skin rash or have no replacement therapy for
endocrinopathies
5. Known human immunodeficiency virus (HIV), active hepatitis B virus
(HBV) or active hepatitis C virus (HCV) infection. Patients with HCC,
whoseHBVorHCVinfectioniscontrolledbyantiviraltherapy,shouldnot
be excluded.
6. Active autoimmune disease or a documented history of autoimmune
disease, including ulcerative colitis and Crohn’s disease or any condition
that requires systemic steroids.
7. Malignant disease, other than that being treated in this study. Exceptions
to this exclusion criterion include malignancies that were treated
curatively and have not recurred within 2 years prior to the first dose of
study treatment; completely resected basal cell and squamous cell skin
cancers; and completely resected carcinoma in situ of any type.
8. Systemic steroidtherapyor anyimmunosuppressive therapy (≥10mg/day
prednisone or equivalent).
9. Anti-CTLA4, anti-PD-(L)1 treatment within 4 weeks of the first dose of
study treatment
10. Pretreatment with anti-CTLA4 antibodies in combination with other
antibodies or drugs, specifically targeting T-cell stimulation or checkpoint
pathways.
11. Systemicanti-cancertherapy(tyrosinekinaseinhibitor(TKI)and/or
chemotherapy) within 2 weeks of the first dose of study treatment. For
cytotoxicagentsthathavemajordelayedtoxicity,e.g.mitomycinCand
nitrosourea, 4 weeks is indicated as washout period.
12. Use of life attenuated vaccines against infectious diseases (e.g.measles
mumps rubella (MMR combined vaccines), Rotavirus, Chickenpox,
yellow fever ) within 4 weeks of initiation of study treatment.
13. Participation in an interventional, investigational study within 4 weeks of
the first dose of study treatment.
14. Impaired cardiac function or clinically significant cardiac disease,
includinganyofthefollowing:
a. Clinically significant and/or uncontrolled heart disease such as
congestive heart failure requiring treatment (New York Heart
Association (NYHA) Grade ≥2), uncontrolled hypertension or
clinically significant arrhythmia
b. QTcF >470 msec on screening electrocardiogram (ECG) or
congenital long QT syndrome
c. Acute myocardial infarction or unstable angina pectoris <3 months
prior to first dose of study treatment
15. PresenceofCommonTerminologyCriteria forAdverseEventsVersion5
(CTCAE v5) ≥Grade 2 toxicity (except alopecia, peripheral neuropathy and
ototoxicity,whichareexcludedifCTCAEv5≥Grade3)duetopriorcancer
therapy.
16. Radiotherapy within 2 weeks of the first dose of study treatment, exceptfor
palliative radiotherapy to a limited field, such as for the treatment of bone
pain or a focally painfultumor mass.To allowevaluation for response to
treatment, patients enrolled in the Phase 2 part must have remaining
measurablediseasethathasnotbeenirradiated.
The Estimated Number of Participants
-
Taiwan
75 participants
-
Global
412 participants
