Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05117476




Registration number
NCT05117476
Ethics application status
Date submitted
2/09/2021
Date registered
11/11/2021
Date last updated
23/05/2024

Titles & IDs
Public title
A Study of CLN-619 Alone and in Combination With Pembrolizumab in Advanced Solid Tumors
Scientific title
A Phase 1 Dose-Escalation Study to Investigate the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamic Activity of CLN-619 (Anti-MICA/MICB Antibody) Alone and in Combination With Pembrolizumab in Patients With Advanced Solid Tumors
Secondary ID [1] 0 0
CLN-619-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumor 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - CLN-619
Treatment: Drugs - Pembrolizumab

Experimental: Module A Dose Escalation - Patients with advanced solid tumors enrolled in dose escalation cohorts treated with CLN-619

Experimental: Module A Cohort Expansion - Patients with select solid tumor types enrolled in expansion cohorts treated with CLN-619 at a dose selected from the Module A Escalation arm

Experimental: Module B Combination Therapy Dose Escalation - Patients with advanced solid tumors enrolled in dose escalation cohorts treated with CLN-619 in combination with pembrolizumab

Experimental: Module B Combination Therapy Cohort Expansion - Patients with select tumor types enrolled in expansion cohorts treated with CLN-619 at a dose selected from the Module B Escalation arm, in combination with pembrolizumab


Treatment: Drugs: CLN-619
Anti-MICA/MICB monoclonal antibody

Treatment: Drugs: Pembrolizumab
Keytruda
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose Escalation: TEAEs
Timepoint [1] 0 0
24 Months
Primary outcome [2] 0 0
Dose Expansion: Best Overall Response (BOR)
Timepoint [2] 0 0
Every 6 weeks for the first 18 weeks and then every 9 weeks until disease progression; approximately 36 months
Primary outcome [3] 0 0
Dose Expansion: Overall Response Rate (ORR)
Timepoint [3] 0 0
Every 6 weeks for the first 18 weeks and then every 9 weeks until disease progression; approximately 36 months
Primary outcome [4] 0 0
Dose Expansion: Duration of Response (DoR)
Timepoint [4] 0 0
Every 6 weeks for the first 18 weeks and then every 9 weeks until disease progression; approximately 36 months
Primary outcome [5] 0 0
Dose Expansion: Disease Control Rate (DCR)
Timepoint [5] 0 0
Every 6 weeks for the first 18 weeks and then every 9 weeks until disease progression; approximately 36 months
Primary outcome [6] 0 0
Dose Expansion: Overall Survival (OS)
Timepoint [6] 0 0
Every 6 weeks for the first 18 weeks and then every 9 weeks until disease progression; approximately 36 months
Primary outcome [7] 0 0
Dose Expansion: Clinical Benefit Rate (CBR)
Timepoint [7] 0 0
Every 6 weeks for the first 18 weeks and then every 9 weeks until disease progression; approximately 36 months
Secondary outcome [1] 0 0
All Cohorts: Cmax
Timepoint [1] 0 0
Up to 2 years
Secondary outcome [2] 0 0
All Cohorts: AUC
Timepoint [2] 0 0
Up to 2 years
Secondary outcome [3] 0 0
All Cohorts: Time to Maximum concentration
Timepoint [3] 0 0
Up to 2 years
Secondary outcome [4] 0 0
All Cohorts: Clast
Timepoint [4] 0 0
Up to 2 years
Secondary outcome [5] 0 0
All Cohorts: Time to last plasma concentration
Timepoint [5] 0 0
Up to 2 years
Secondary outcome [6] 0 0
All Cohorts: Half-life
Timepoint [6] 0 0
Up to 2 years
Secondary outcome [7] 0 0
All Cohorts: Volume of Distribution
Timepoint [7] 0 0
Up to 2 years

Eligibility
Key inclusion criteria
1. Males or females aged = 18 years.

2. Willing and able to give written informed consent and adhere to protocol requirements;
written informed consent and any locally required authorization must be obtained from
the patient prior to performing any protocol-related procedures, including screening
evaluations.

3. Module A Monotherapy Dose Escalation Cohort and Module B Combination Therapy Dose
Escalation Cohorts: Histologically or cytologically-confirmed metastatic or locally
advanced, unresectable solid tumors. For Module B, tumor type is listed as an approved
indication per the current prescribing information for pembrolizumab.

4. Module A Cohort Expansions:

1. Expansion A1: Histologically or cytologically-confirmed metastatic or locally
advanced, unresectable NSCLC;

2. Expansion A2: Histologically or cytologically-confirmed metastatic or locally
advanced, unresectable cervical cancer.

3. Expansion A3 and A4: Histologically or cytologically-confirmed metastatic or
locally advanced, unresectable endometrial cancer.

4. Eligibility for disease-specific expansion cohorts may be further refined by
histologic subtype, molecular features, or exposure to prior therapy based on
clinical, pharmacodynamic, or biomarker data emerging from the study.

5. Module B Cohort Expansions:

1. Expansion B1: Histologically or cytologically-confirmed metastatic or
locally-advanced, unresectable NSCLC.

2. Expansion B2: Histologically or cytologically-confirmed metastatic or
locally-advanced, unresectable endometrial.

3. Eligibility for disease-specific expansion cohorts may be further refined by
histologic subtype, molecular features, or exposure to prior therapy based on
clinical, pharmacodynamic, or biomarker data emerging from the study.

6. Prior treatment history as follows:

a) Patients should have received any other approved standard therapy that is available
to the patient, unless this therapy is contraindicated, intolerable to the patient, or
is declined by the patient. In the case of a patient declining such therapy,
documentation that the patient has been informed and declined should be documented in
the medical record.

7. Baseline measurable disease based on RECIST v1.1 for Module A escalation, Module B
escalation; and, both Module A and Module B expansion cohorts. Patients are required
to have one or more measurable lesions that meet RECIST v1.1 and meet the following
conditions:

1. A non-lymph node lesion that has a longest unidimensional measurement of = 10 mm
or a lymph node lesion that has a shortest unidimensional measurement of = 15 mm;

2. Lesions that have received previous local treatment, such as radiotherapy or
ablation, can also be used as measurable target lesions if progression has been
confirmed according to RECIST v1.1 prior to enrollment, and the longest
unidimensional measurement is = 10 mm.

8. Performance status of 0 or 1 based on the Eastern Cooperative Oncology Group (ECOG)
performance scale.

9. Estimated life expectancy of 12 weeks or greater.

10. Prior palliative radiotherapy must have been completed 14 days prior to dosing on
C1D1.

11. Toxicities related to prior study therapy should have resolved to Grade 1 or less
according to criteria of NCI CTCAE v5.0, except for alopecia. Peripheral neuropathy
should be clinically stable or improving and be Grade 2 or less in severity. Patients
with chronic but stable Grade 2 toxicities may be allowed to enroll after agreement
between the Investigator and Sponsor.

12. Have adequate liver and kidney function and hematological parameters within a normal
range as defined by:

1. Total bilirubin = 1.5x ULN. This does not apply for patients with confirmed
Gilbert's Syndrome, for whom total bilirubin must be less than 3.0 mg/dL with a
conjugated bilirubin less than 0.5 mg/dL;

2. AST and ALT = 2.5x ULN or = 5x ULN for patients with liver metastases;

3. Creatinine clearance (CrCl) = 45 mL/min as measured or estimated using
Cockcroft-Gault formula;

4. Hemoglobin = 8 g/dL without blood transfusions for at least two weeks prior to
dosing on C1D1;

5. Absolute neutrophil count = 1500 cells/mm3 without growth factor support, three
days for filgrastim, 14 days for pegfilgrastim;

6. Platelet count = 75,000 cells/mm3.

13. Patients in the Module A and Module B dose escalation cohorts must have archival
tissue for biomarker analysis. A fresh biopsy is required if archival tissue is
unavailable.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Currently participating/previously participated in an interventional study and
received an investigational drug within 28 days (or five half-lives, whichever is
longer) of dosing on C1D1.

2. Patients with concomitant second malignancies (except adequately treated
non-melanomatous skin cancers, ductal carcinoma in situ, superficial bladder cancer,
prostate cancer or in situ cervical cancer) are excluded unless in complete remission
three years prior to study entry, and no additional therapy is required or anticipated
to be required during study participation.

3. Patients with any active autoimmune disease or a history of known or suspected
autoimmune disease, or history of a syndrome that requires systemic corticosteroids or
immunosuppressive medications, except for patients with vitiligo, resolved childhood
asthma/atopy or autoimmune thyroid disorders on stable thyroid hormone
supplementation.

4. A serious uncontrolled medical disorder that would impair the ability of the patient
to receive protocol therapy or whose control may be jeopardized by the complications
of this therapy. These criteria include, but are not limited to the following:

1. Uncontrolled airway hyper-reactivity;

2. Type 1 diabetes mellitus. Type 2 diabetes mellitus patients are allowed if they
are under stable glycemic control as per Investigator assessment;

3. Uncontrolled, clinically significant pulmonary disease;

4. Requirement for supplemental oxygen to maintain a pulse ox > 93%;

5. Symptomatic congestive heart failure as per Investigator assessment or documented
cardiac ejection fraction less than 45%;

6. Ejection fraction < 45% in patients with prior history of treatment with
anthracycline chemotherapy or with a prior history of cardiac ventricular
dysfunction. Patients with prior history of ventricular dysfunction or
anthracycline therapy are required to have an echocardiogram for assessment of
baseline cardiac function;

7. History of unstable angina or myocardial infarction within six months of dosing
on C1D1;

8. Unstable cardiac arrhythmia;

9. History of ventricular arrhythmia;

10. Uncontrolled hypertension: patients with sustained systolic blood pressure
readings greater than 150 or diastolic blood pressure greater than 100 should
have documentation by treating physician that the finding is not consistent with
uncontrolled hypertension;

11. History of stroke or cerebral hemorrhage within one year of dosing on C1D1;

12. Poorly controlled seizure disorder;

13. Active diverticulitis within one year prior to dosing on C1D1;

14. Recent major surgery within three months of dosing on C1D1 or major surgery with
unresolved complications that could interfere with study treatment.

5. Treatment with systemic antiviral, antibacterial or antifungal agents for acute
infection within = 7 days of dosing on C1D1.

6. Has a history of, or a positive test for, HIV1/2 primary immunodeficiency disease such
as Human Immunodeficiency Virus (HIV).

7. Diagnosed with hepatitis B (with positive testing for either hepatitis B surface
antigen [HBsAg] or hepatitis B core Ab) or hepatitis C (HCV) infection (with positive
testing for HCV antibody and/or HCV ribonucleic acid [RNA] in serum) under any of the
following conditions:

1. Active disease for hepatitis B or hepatitis C and received antiretroviral therapy
within 4 weeks.

2. Blood hepatitis B DNA or HCV RNA are detectable.

8. Prior organ allograft or allogeneic hematopoietic transplantation.

9. History of the following events in conjunction with prior treatment with checkpoint
inhibitor immunotherapy: Grade 3 or greater neurotoxicity, ocular toxicity,
pneumonitis, myocarditis, or colitis; liver dysfunction meeting the laboratory
criteria for Hy's Law.

10. Active central nervous system metastases and/or carcinomatous meningitis. Patients
with brain metastases identified at Screening may be rescreened after they have been
appropriately treated. Patients with treated brain metastases should be neurologically
stable for 28 days post completion of treatment and prior to enrollment, and on a
stable regimen of steroid dosing (prednisone <10 mg or the equivalent) for 14 days
prior to dosing on C1D1.

11. Treatment with non-oncology vaccines for the control of infectious diseases (i.e. HPV
vaccine) within 28 days of C1D1. The inactivated seasonal influenza vaccine can be
given to patients before initiation of treatment, and while on study therapy without
restriction. Influenza vaccines containing live virus, or other clinically indicated
vaccinations for infectious diseases (i.e. pneumovax, varicella) may be permitted, but
must be discussed in advance with the Sponsor Medical Monitor and may require a study
drug washout period before and/or after administration of the vaccine. Covid-19
vaccines may be administered according to institutional policy.

12. Active SARS-CoV-2 infection including history of positive SARS-CoV-2 testing without
subsequent documentation of negative test results, patients with results that are
pending but not yet known, or patients with suspected active infection based on
clinical features.

SARS-CoV-2 vaccination is permitted on treatment.

13. Has received immunosuppressive medications including but not limited to cellcept,
methotrexate, infliximab, anakinra, tocilizumab, cyclosporine or corticosteroids (=10
mg/day of prednisone or equivalent), within 28 days of dosing on C1D1.

14. Female of child-bearing potential (FOCBP) who is pregnant or breast-feeding, plans to
become pregnant within 120 days of last study drug administration, or declines to use
an acceptable method to prevent pregnancy during study treatment and for 120 days
after the last dose of study drug administration.

a) A female of childbearing potential is defined as: i) Not surgically sterile, i.e.
bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy, or; ii)
Not post-menopausal, defined as amenorrhea for = two years without an alternative
medical cause.

Note: Females with amenorrhea for < two years and who are not surgically sterile i.e.
tubal ligation, bilateral oophorectomy, or complete hysterectomy will only be
considered not to be of reproductive potential if they have a documented follicle
stimulating hormone (FSH) value in the postmenopausal range.

15. Male patient who plans to father a child or donate sperm within 120 days or 5
half-lives of CLN-619, whichever comes later, of last study drug administration, or
who has a partner who is a FOCBP, and declines to use acceptable method to prevent
pregnancy during study treatment and for 120 days or 5 half-lives of CLN-619,
whichever comes later, after the last dose of study drug administration.

16. QT interval corrected for heart rate using Fridericia's formula (QTcF) of = 500
milliseconds.

17. Patient has history of drug-related anaphylactic reactions to any components of
CLN-619 (Module A and Module B patients) or pembrolizumab (Module B patients only).
History of Grade 4 anaphylactic reaction to any monoclonal antibody therapy.

18. Known active alcohol or drug abuse.

19. Inability to comply with the protocol and/or not willing or not available for
follow-up assessments.

20. Patients who are incapacitated or involuntarily incarcerated.

21. Patients who are unsuitable for participation based on the judgement of the
Investigator.

22. Treatment with any of the following:

1. Systemic anticancer treatment within 14 days prior to the first dose of study
drug on C1D1.

2. Immunotherapy = 28 days prior to the first dose of study drug on C1D1.

3. Radiotherapy < 28 days and palliative radiation = 14 days prior to the first dose
of study drug on C1D1. If irradiated, lesions must have demonstrated clear-cut
progression prior to being eligible for evaluation as target lesions.

4. Major surgery (excluding placement of vascular access) = 28 days of the first
dose of study drug on C1D1.

23. Refractory disease will be defined as progressive disease at 16 weeks after receiving
at least three doses of PD-1 therapy (Expansion B2 and Expansion B3 only).

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/10/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/06/2026
Actual
Sample size
Target
410
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC,WA
Recruitment hospital [1] 0 0
Monash Health - Clayton
Recruitment hospital [2] 0 0
Alfred Health - Melbourne
Recruitment hospital [3] 0 0
Linear Clinical Research - Nedlands
Recruitment postcode(s) [1] 0 0
3168 - Clayton
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
New Jersey
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
North Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Tennessee
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
Virginia
Country [11] 0 0
Poland
State/province [11] 0 0
Józefów
Country [12] 0 0
Poland
State/province [12] 0 0
Poznan
Country [13] 0 0
Poland
State/province [13] 0 0
Warsaw
Country [14] 0 0
Spain
State/province [14] 0 0
Barcelona
Country [15] 0 0
Spain
State/province [15] 0 0
Madrid
Country [16] 0 0
Spain
State/province [16] 0 0
Pamplona
Country [17] 0 0
Spain
State/province [17] 0 0
Sabadell

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Cullinan Therapeutics Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
CLN-619-001 is a Phase 1, open-label, multi-center study of CLN-619 alone and in combination
with pembrolizumab in patients with advanced solid tumors.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05117476
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Timna O Serino
Address 0 0
Country 0 0
Phone 0 0
+1 617 410 4650
Fax 0 0
Email 0 0
ClinOps@cullinantx.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05117476