A Multicenter, Phase 4, Open label, Single-arm, Safety Study of Enfortumab Vedotin in Adult Indian Participants with Previously Treated Locally Advanced or Metastatic Urothelial Cancer
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 15
- 主要终点
- To evaluate the safety and tolerability of EV in adult Indian participants with LA or mUC
研究概览
简要总结
Title of Study:
A Multicenter, Phase 4, Open-label, Single-arm, Safety Study of Enfortumab Vedotin in Adult Indian Participants with Previously Treated Locally Advanced or Metastatic Urothelial Cancer
Short Title of Study:
A Safety Study of Enfortumab Vedotin in Indian Adults with Urothelial Cancer
Regulatory Agency Identifier Number(s):
Not applicable.
Planned Total Number of Study Sites and Location(s):
Approximately 10 study sites (geographically diverse) in India.
Note: The number of study sites may be adjusted based on participant enrollment.
Rationale:
The primary objective of this study is to assess the safety and tolerability of enfortumab vedotin monotherapy in Indian participants with LA or mUC. The study will also evaluate antitumor activity of enfortumab vedotin in Indian participants. No differences are anticipated in safety, tolerability and efficacy of enfortumab vedotin based on ethnicity from the phase 1, 2, and 3 studies conducted to date. This protocol is part of the post-marketing commitment to the Indian Health Authority after the approval of enfortumab vedotin based on Study 7465-CL-0301 (NCT03474107).
Study Objectives, Endpoints and Estimands:
| Objectives |
Endpoints
|Primary
|To evaluate the safety and tolerability of EV in
adult Indian participants with LA or mUC
Safety variables
o AEs
o laboratory tests
o vital sign measurements
o 12-lead ECG
o ECOG performance status
|Secondary
|To evaluate the anti-tumor activity of EV as
determined by investigator assessment
- Confirmed ORR according to RECIST version
1.1 per investigator assessment
- DOR according to RECIST version 1.1 per
investigator assessment
AE: adverse event; DOR: duration of response; ECG: electrocardiogram; ECOG: Eastern Cooperative Oncology Group; EV: enfortumab vedotin; LA: locally advanced; mUC: metastatic urothelial cancer;
ORR: objective response rate; RECIST: Response Evaluation Criteria in Solid Tumours.
Primary Estimand :
Not applicable.
Study Population:
Adult male and female Indian participants with previously treated LA or mUC.
Number of Participants:
One hundred participants will be enrolled.
Study Design Overview:
This is a multicenter, phase 4, open-label, single-arm, safety study of enfortumab vedotin in adult Indian participants with LA or mUC who have received a platinum-containing chemotherapy and have experienced disease progression or relapse during or following treatment with an immune CPI. The study will be conducted at approximately 10 sites (geographically diverse) in India and will enroll 100 participants. The number of study sites may be adjusted based on participant enrollment.
The single-arm study will consist of 3 periods:
• Screening/Baseline period: for a maximum of 28 days prior to the first dose of study intervention defined as cycle 1 day 1.
• Treatment period: beginning at cycle 1 and subsequent cycles until participant discontinues study intervention.
• Follow-up period: beginning after participant discontinues study intervention.
Screening/Baseline Period
After informed consent has been obtained, participants will be evaluated for eligibility by review of medical history, physical examination, weight, vital signs (pulse, temperature and blood pressure),
eye examination, ECOG performance status, imaging assessments (i.e., brain scan and bone scan), blood sample collection and ECG. AEs will be collected during this period. Screening assessments
may be repeated within the 28-day screening period. Participants may only be rescreened once.
Treatment Period
All participants will receive enfortumab vedotin on days 1, 8 and 15 of each 28-day cycle. Participants will continue to receive study intervention until any discontinuation criteria are met, upon study termination or study completion, whichever occurs first. An EOT visit will be performed within 7 days after the last dose of enfortumab vedotin or the decision to discontinue treatment, or prior to initiation of another anticancer therapy, whichever occurs earlier.
Follow-up Periods
30-day Safety Follow-up: Following discontinuation from study intervention or until initiation of a new anticancer treatment, participants will have a 30-day safety follow-up visit 30 days (+ 7 days) after their last dose of study intervention for safety assessments. Post-treatment Follow-up: Participants who discontinue study intervention for reasons other than objective disease progression by RECIST version 1.1 will continue to have response assessments every 8 weeks (± 1 week) following the previous visit thereafter. After 1 year from cycle 1 day 1, the frequency of response assessments will be reduced to every 12 weeks (± 1 week). The tumor assessments will continue until the participant has radiological disease progression per RECIST version 1.1 as determined by investigator assessment, initiates a new anticancer therapy, death, lost to follow-up, study closure, or withdrawal of consent, whichever comes first. The end of the study is defined as the last visit or assessment shown in schedule of assessments for the last participant in the study.
A participant is considered to have completed the study if the participant has completed all periods of the study including the last assessment shown in the schedule of assessments.
Study Intervention Groups and Duration:
| Intervention Label |
Enfortumab vedotin
|Intervention Name
Enfortumab vedotin
|Type
Drug
|Pharmaceutical Dose Form
Solution for injection
|Unit Dose Strength(s)
1.25 mg/kg (maximum dose 125 mg)
|Dosage Level(s)
On days 1, 8, and 15 of a 28-day cycle
|Route of Administration
Intravenous infusion
|Use
Experimental
|IMP and NIMP/AxMP
IMP
|Intended Sourcing****1
Provided centrally by sponsor
|Packaging and Labeling
Supplied as lyophilized powder in single-dose vial for reconstitution
AxMP: auxiliary medicinal product; IMP: investigational medicinal product; NIMP: noninvestigational medicinal
product.
- Planned sourcing may be subject to change based on product availability The anticipated duration of the study for each participant, including screening and follow-up, is approximately 14 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Participant is more than or equal to 18 years of age at the time of signing the ICF. Type of Participant and Disease Characteristics
- •Participant has histologically or cytologically confirmed urothelial carcinoma (i.e., cancer of the bladder, renal pelvis, ureter or urethra). Participants with urothelial carcinoma (transitional cell) with squamous differentiation or mixed cell types are eligible.
- •Participant must have experienced radiographic progression or relapse during or after a CPI (anti-PD-1 or anti-PD-L1) for LA or metastatic disease. Participants who discontinued CPI treatment due to toxicity are eligible provided that they have evidence of disease progression following discontinuation. The CPI need not be the most recent therapy. Participants for whom the most recent therapy has been a non-CPI based regimen are eligible if they have progressed/relapsed during or after their most recent therapy. LA disease must not be amenable to resection with curative intent per the treating physician.
- •Participant must have received a platinum-containing regimen (cisplatin or carboplatin) in the metastatic/LA, neoadjuvant or adjuvant setting. If platinum was administered in the adjuvant/neoadjuvant setting, the participant must have progressed within 12 months of completion.
- •Participant must have measurable metastatic or LA disease at baseline according to RECIST version 1.
- •Participant has ECOG performance status of 0 or
- •Participant has the following baseline laboratory data.
- •ANC more than or equal to 1500/cubic mm.
- •Platelet count more than or equal to 100000000000/L.
- •CrCl more than or equal to 30 mL/min as estimated per institutional standards or as measured by 24-hour urine collection (GFR can also be used instead of CrCl).
- •ALT and AST less than or equal to 2.5 × ULN or less than or equal to 3 × ULN for participants with liver metastases.
- •Female participant: • Not pregnant (see [Section 10.2]) and at least 1 of the following conditions apply: a. Not a WOCBP (see [Section 10.2]) b. WOCBP who has a negative urine or serum pregnancy test at screening or within 7 days prior to day 1 and agrees to follow the contraceptive guidance (see [Section 10.2]) from the time of informed consent through at least 6 months after final study intervention administration. • Must not be breastfeeding or lactating starting at screening and throughout the investigational period and for approximately 6 months after final study intervention administration. • Must not donate ova starting at first administration of study intervention and throughout the investigational period and for 6 months after final study intervention administration.
- •Male participant: • Must agree to use contraception (see [Section 10.2]) with female partner(s) of childbearing potential (including breastfeeding partner) throughout the treatment period and for 6 months after final study intervention administration. • Must agree to remain abstinent or use a condom with pregnant partner(s) for the duration of the pregnancy throughout the investigational period and for 6 months after final study intervention administration. • Must not donate sperm during the treatment period and for 6 months after final study intervention administration. Informed Consent
- •Participant has provided informed consent as described in [Section 10.1.3] which includes compliance with the requirements and restrictions listed in the ICF and protocol. Other Inclusion Criteria
- •Participant agrees not to participate in another interventional study while receiving study intervention in the present study.
排除标准
- •Medical Conditions
- •Participant has preexisting sensory or motor neuropathy grade more than or equal to
- •Participant has active CNS metastases. Participant with treated CNS metastases is permitted on study if all the following are true:.
- •CNS metastases have been clinically stable for at least 6 weeks prior to screening.
- •If requiring steroid treatment for CNS metastases, the participant is on a stable dose less than or equal to 20 mg/day of prednisone or equivalent for at least 2 weeks.
- •Baseline scans show no evidence of new or enlarged brain metastasis.
- •Participant with less than or equal to grade 2 immunotherapy-related hypothyroidism or panhypopituitarism may be enrolled when well-maintained/controlled on a stable dose of HRT (if indicated).
- •Participant with ongoing more than or equal to grade 3 immunotherapy-related hypothyroidism or panhypopituitarism are excluded. Participant with ongoing immunotherapy-related colitis, uveitis, myocarditis or pneumonitis, or participant with other immunotherapy-related AEs requiring high doses of steroids (more than 20 mg/day of prednisone or equivalent) are excluded.
- •Participant has history of another malignancy within 3 years before the first dose of study intervention or any evidence of residual disease from a previously diagnosed malignancy.
- •Participant with non-melanoma skin cancer, localized prostate cancer treated with curative intent with no evidence of progression, low-risk or very low-risk (per standard guidelines) localized prostate cancer under active surveillance/watchful waiting without intent to treat, or carcinoma in situ of any type (if complete resection was performed) are allowed.
- •Participant with a positive hepatitis B surface antigen and/or anti-hepatitis B core antibody and a negative polymerase chain reaction assay at baseline should receive appropriate antiviral prophylaxis or regular surveillance monitoring as per local or institutional guidelines.
- •Participant has active hepatitis C infection or known human immunodeficiency virus infection. Participant who has been treated for hepatitis C infection is permitted if they have documented sustained virologic response of more than or equal to 12 weeks.
- •Participant has documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms (including congestive heart failure) consistent with New York Heart Association Class III to IV within 6 months prior to the first dose of study intervention administration.
- •Participant has known active keratitis or corneal ulcerations. Participant with superficial punctate keratitis is allowed if the disorder is being adequately treated in the opinion of the investigator.
- •Participant has other underlying medical condition that, in the opinion of the investigator, would impair the ability of the participant to receive or tolerate the planned treatment and follow-up.
- •Participant has history of uncontrolled diabetes mellitus within 3 months of the first dose of study intervention. Uncontrolled diabetes is defined as HbA1c more than or equal to 8% or HbA1c between 7% and less than 8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained. Prior/Concomitant Therapy
- •Participant has prior treatment with enfortumab vedotin or other MMAE-based ADCs.
- •Participant is currently receiving systemic antimicrobial treatment for viral, bacterial, or fungal infection at the time of first dose of enfortumab vedotin. Routine antimicrobial prophylaxis is permitted.
- •Participant has radiotherapy or major surgery within 4 weeks prior to first dose study intervention administration.
- •Participant has had chemotherapy, biologics, investigational agents, and/or antitumor treatment with immunotherapy that is not completed 2 weeks prior to first dose of study intervention administration. Other Exclusion Criteria
- •Participant has any condition, which, in the investigator’s opinion, makes the participant unsuitable for study participation.
- •Participant has a known or suspected hypersensitivity to enfortumab vedotin or to any excipient contained in the drug formulation of enfortumab vedotin (including histidine, trehalose dihydrate, and polysorbate 20); OR participant has known hypersensitivity to biopharmaceuticals produced in CHO cells.
结局指标
主要结局
To evaluate the safety and tolerability of EV in adult Indian participants with LA or mUC
时间窗: Every 8 weeks
次要结局
- To evaluate the anti-tumor activity of EV as determined by investigator assessment(Every 8 weeks)
研究者
Dr Amit Joshi
Tata Memorial Centre Tata Memorial Hospital