A Phase 1, Open-Label, Multicenter, Dose Escalation and Cohort Expansion Study of the Safety and Efficacy of Allogeneic CRISPR-Cas9-Engineered T Cells (CTX130) in Adult Subjects with Advanced, Relapsed or Refractory Renal Cell Carcinoma (RCC) with Clear Cell Differentiatio
- Conditions
- clear cell renal cell carcinomakidney cancer10038364
- Registration Number
- NL-OMON54482
- Lead Sponsor
- CRISPR Therapeutics AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 8
1. >=18 years of age and body weight >=42 kg.
2. Able to understand and comply with protocol-required study procedures and
voluntarily sign a written informed consent document.
3. Diagnosed with unresectable or metastatic RCC with clear cell
differentiation:
• Have previous exposure to both a CPI and a VEGF inhibitor and documented
progression after adequate exposure for favorable risk by International
Metastatic RCC Database Consortium criteria or a lack of response and/or
progression after adequate exposure for intermediate and poor risk
characteristics.
• Have a previously pathologically confirmed diagnosis of RCC with clear cell
differentiation.
• Availability of tumor tissues.
• Have measurable disease as assessed by the investigator/site radiologist per
RECIST v1.1. Target lesions situated in a previously irradiated area are
considered measurable if progression has been demonstrated in such lesions.
• Have at least 1 nontarget lesion that is suitable for biopsies.
4. Karnofsky performance status >=80% as assessed during the screening period.
5. Meets protocol-specified criteria to undergo daratumumab administration
(Parts A3 and A4 only), LD chemotherapy and CAR T cell infusion.
6. Adequate organ function:
• Renal: Creatinine clearance >=50 mL/min.
• Liver:
* Aspartate aminotransferase and alanine aminotransferase < 3 x upper limit of
normal (ULN)
* Total bilirubin <2 x ULN (for Gilbert*s syndrome: total bilirubin < 3 mg/dL
and normal conjugated bilirubin)
* Albumin >90% of lower limit of normal.
• Cardiac: Hemodynamically stable and left ventricular ejection fraction >=45%
by echocardiogram.
• Pulmonary: Oxygen saturation level on room air >92% per pulse oximetry.
• Hematologic: Platelet count >100,000/mm^3, absolute neutrophil count
>1500/mm^3, and hemoglobin >9 g/dL without prior blood cell transfusion before
screening.
• Coagulation: Activated partial thromboplastin time or partial thromboplastin
time <=1.5 x ULN.
7. Female subjects of childbearing potential (postmenarcheal, has an intact
uterus and at least 1 ovary, and is less than 1 year postmenopausal) must agree
to use a highly effective method of contraception (as specified in the
protocol) from enrollment through at least 12 months after last CTX130
infusion.
8. Male subjects must agree to use acceptable effective method of contraception
(as specified in the protocol) from enrollment through at least 12 months after
last CTX130 infusion.
1. Prior treatment with any anti-CD70 targeting agents.
2. Prior treatment with any CAR T cells or any other modified T or natural
killer cells.
3. Known contraindications to daratumumab (Parts A3 and A4 only) any LD
chemotherapy agent(s) or any of the excipients of CTX130 product.
4. Subjects with central nervous system (CNS) manifestation of their malignancy
as evidenced by positive screening MRI or past history.
5. History or presence of clinically relevant CNS pathology such as seizure,
stroke, severe brain injury, cerebellar disease, history of posterior
reversible encephalopathy syndrome with prior therapy, or another condition
that in opinion of the investigator may increase CAR T cell-related toxicities.
6. Ongoing, clinically significant pleural effusion, or ascites or any
pericardial effusion, or a history of
pleural effusion or ascites in the last 2 months.
7. Unstable angina, clinically significant arrhythmia per investigator*s
judgement, or myocardial infarction within 6 months prior to screening.
8. Diabetes mellitus with a current hemoglobin A1c level of >7.0%.
9. Ongoing bacterial, viral, or fungal infection, requiring systemic
anti-infectives.
10. Positive for presence of human immunodeficiency virus type 1 or 2, or
active hepatitis B virus or hepatitis C virus infection. Subjects with prior
history of hepatitis B or C infection who have documented undetectable viral
load (by quantitative polymerase chain reaction or nucleic acid testing) are
permitted.
11. Previous or concurrent malignancy, except those treated with curative
approach not requiring systemic therapy and have been in remission for >12
months, or any other localized malignancy that has a low risk of developing
into metastatic disease, per investigator*s judgement.
12. Primary immunodeficiency disorder or active autoimmune disease requiring
steroids and/or any other immunosuppressive therapy.
13. Prior solid organ transplantation or bone marrow transplant.
14. Use of systemic antitumor therapy or investigational agent, including
radiotherapy, within 14 days prior to enrollment. Use of physiological doses of
steroids (e.g. <=10mg/day prednisone or equivalent) will be permitted for
subjects previously on steroids if clinically indicated.
15. Received live vaccines or herbal medicines as part of traditional Chinese
medicine or non-over-the-counter herbal remedies within 28 days prior to
enrollment.
16. Diagnosis of significant psychiatric disorder that could seriously impede
the subject*s ability to participate in the study.
17. Pregnant or breastfeeding females.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Parts A1, A3 (Single Dose Escalation): Incidence of adverse events (AEs),<br /><br>defined asdose-limiting toxicities (DLTs).<br /><br>Parts A2, A4 (Multiple Dose Regimen): Incidence of AEs after multiple doses of<br /><br>CTX130.<br /><br>Part B (cohort expansion): ORR, defined as the proportion of subjects who have<br /><br>achieved a best overall response of complete response (CR) or partial response<br /><br>(PR) according to RECIST v1.1, as assessed by an Independent Review Committee<br /><br>(IRC). </p><br>
- Secondary Outcome Measures
Name Time Method <p>• To further characterize the efficacy of CTX130 over time<br /><br>• To further assess the safety of CTX130, and to describe and assess adverse<br /><br>events (AEs) of interest, including cytokine release syndrome (CRS), tumor<br /><br>lysis syndrome and Graft versus Host Disease (GvHD)<br /><br>• To characterize pharmacokinetics (PK) (expansion and persistence) of CTX130<br /><br>in blood</p><br>