This study has been transitioned to CTIS with ID 2023-506384-34-00 check the CTIS register for the current data. Primary:- To assess the safety and tolerability of MK2140- To evaluate objective response rate (ORR) of MK2140 as assessed by BICR per…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms benign
- Bladder and bladder neck disorders (excl calculi)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Adverse Events (AEs)
- Study intervention discontinuations due to AEs.
- Objective Response (OR): Complete response (CR) or partial response (PR)
Secondary outcome
Duration of response (DOR): For participants who demonstrate CR or PR, DOR is
defined as the time from the first documented evidence of CR or PR until
disease progression or death due to any cause, whichever occurs first.
Background summary
Locally advanced or mUC is a serious and incurable condition with poor
long-term survival and a high unmet medical need
Anti-PD-1/L1 agents are approved for the adjuvant treatment of high-risk
muscle-invasive bladder cancer and for the treatment of locally advanced and
mUC in the 1L setting for cisplatin-ineligible patients with PD-L1 CPS >=10; for
patients who are not eligible for any platinum-containing chemotherapy,
regardless of PD-L1 status, and as maintenance therapy for a subset of patients
that have received platinum-based chemotherapy. Anti-PD-1/L1 agents are also
approved in the 2L setting in patients deemed platinum refractory UC. Despite
the durable clinical benefits from the use of these agents, a large portion of
patients have disease that either shows no clinical response or response
followed by progression requiring subsequent therapies.
The patients who respond best to anti-PD-1/L1 therapies have a longer OS, but
those with no response quickly develop progressive disease. The Society for
Immunotherapy of Cancer taskforce has generated clinical definitions for
resistance to PD-1/L1 inhibitors in 3 distinct scenarios: 1) primary
resistance, 2) secondary resistance, and 3) disease progression after
discontinuation or halting of PD-1/L1 inhibitors. This patient population
resistant to immunotherapy represents a significant unmet medical need because
of very limited available treatment options and therefore necessitates the
development of new therapies.
The study drug MK2140 in this study may improve responsiveness in tumors that
are resistant or refractory to anti-PD-1/L1 therapy.
Study objective
This study has been transitioned to CTIS with ID 2023-506384-34-00 check the CTIS register for the current data.
Primary:
- To assess the safety and tolerability of MK2140
- To evaluate objective response rate (ORR) of MK2140 as assessed by BICR per
RECIST 1.1
Secondary:
-To evaluate the duration of response (DOR) of MK2140 as assessed by BICR per
RECIST 1.1
Study design
This is a Phase 1/2 Substudy of MK2140 in PD-1/L1 Refractory Locally Advanced
or mUC.
The study will be perfomed in individuals at least 18 years of age with PD-1/L1
refractory locally advanced/unresectable or metastatic UC receiving MK2140.
This substudy protocol employs a design in which new investigational treatment
arms will be open for enrollment on a rolling basis to evaluate new
investigational treatments with or without pembrolizumab. Therefore, the total
number of participants will depend on the number of investigational treatment
arms open for enrollment
Approximately 40 participants will be enrolled in this study.
The total number of investigational treatment arms will depend on the number of
investigational agents evaluated.
In this current first arm A all subjects will receive MK2140 as an IV infusion
in 3-weekly cycles where MK2140 is given on day 1 and 8 of each cycle.
Intervention
The total number of investigational treatment arms will depend on the number of
investigational agents evaluated. This study protocol will include
a minimum of 1 investigational treatment arm (arm A).
In arm A the interventional agent is MK2140 which is given on day 1 and day 8
of each Q3W cycle. ( please refer to protocol section 10.6.2.2)
MK2140 is a solution for infusion in a unit dose of 10 mg/ml given at 2 mg/kg
as IV infusion
Study burden and risks
For this study, subjects will be exposed to invasive procedures such as biopsy,
blood collection, IV infusions, CT-MRI or bone scans, physical exams and
patients will be asked to visit the hospital regularly.
Patients will receive IMP on day 1 and 8 of three-week cycles. It cannot be
guaranteed that participants in clinical studies will directly benefit from
study intervention during participation, as clinical studies are designed to
provide information about the safety and effectiveness of an investigational
medicine.
Waarderweg 39
Haarlem 2031 BN
NL
Waarderweg 39
Haarlem 2031 BN
NL
Listed location countries
Age
Inclusion criteria
1. Has a histologically or cytologically confirmed diagnosis of locally
advanced/unresectable or mUC of the renal pelvis, ureter (upper urinary tract),
bladder, or urethra. Participants with nonurothelial tumors,including pure
squamous cell carcinoma, pure adenocarcinoma including
urachal adenocarcinomas, neuroendocrine tumors, and mesenchymal tumors, are not
eligible.
2. Has measurable disease as assessed by the site and verified by blinded
independent central review (BICR) according to RECIST 1.1.
3. Has PD-1/L1 refractory locally advanced or mUC as evidenced by:
EITHER disease progression while on treatment or after treatment with an
anti-PD-1/L1 mAb for locally advanced/unresectable or mUC administered either
as monotherapy, or in combination with other checkpoint inhibitors or other
therapies. In these participants, anti-PD-1/L1 mAb treatment is defined by
meeting ALL of the following criteria:
a. Has received at least 2 doses of an approved anti-PD-1/L1 mAb.
b. Has demonstrated radiographic disease progression while on treatment or
after treatment with an anti-PD-1/L1 mAb by investigator assessment.
c. Disease progression has been documented radiographically by the investigator
within 12 weeks from the last dose of anti-PD-1/L1 mAb.
OR
Has experienced disease recurrence while on treatment or after treatment with
an anti-PD-1/L1 mAb for muscle-invasive UC (MIUC) administered as monotherapy.
In these participants, anti-PD-1/L1 mAb treatment is
defined by meeting ALL of the following criteria:
a. Has received at least 2 doses of an approved anti-PD-1/L1 mAb.
b. Has demonstrated radiographic disease recurrence while on treatment with an
anti-PD-1/L1 mAb or within 6 months from treatment completion by investigator
assessment.
4. Participants who received an anti-PD-1/L1 mAb for the treatment of locally
advanced/unresectable or mUC must have demonstrated disease progression while
on treatment or after treatment with an anti-PD-1/L1 mAb based on investigator
assessment. If available, scans before treatment with an anti-PD-1/L1 or
showing nadir during treatment with an anti-PD-1/L1 mAb and scans that document
radiographic disease progression within 12 weeks (84 days) from the last dose
of an anti-PD-1/L1 mAb should be submitted to the iCRO.
Participants who received an anti-PD-1/L1 mAb for the treatment of MIUC must
have demonstrated disease recurrence while on treatment or within 6 months from
treatment completion based on investigator assessment. If available, scan
before treatment with an anti-PD-1/L1 mAb and scan that documents radiographic
recurrence should be submitted to the iCRO.
5. Participants must provide an archival tumor tissue sample or newly obtained
core or excisional biopsy of a tumor lesion demonstrating UC, not previously
irradiated, and adequate for biomarker evaluation. A newly obtained biopsy is
strongly preferred, but not required if archival tissue is evaluable.
6. Has an ECOG performance status of 0 to 1 (as assessed within 7 days of the
first dose of study intervention).
7. Has resolution of toxic effect(s) of the most recent prior therapy to Grade
1 or less (except alopecia).
8. Has adequate organ function. Specimens must be collected within 7 days
before the start of study intervention.
9. Participants are male or female, >=18 years of age at the time of providing
documented informed consent.
10. Male participants are eligible to participate if they agree to follow the
contraception requirements for the investigational treatment arm to which they
are assigned.
• Contraceptive use by men should be consistent with local regulations
regarding the methods of contraception for those participating in clinical
studies. If the contraception requirements in the local label for any of the
study interventions is more stringent than the requirements above,
the local label requirements are to be followed.
11. Female participants are eligible to participate if they agree to follow the
contraception requirements for the investigational treatment arm to which they
are assigned.
12. The participant (or legally acceptable representative) has provided
documented informed consent for the study.
Exclusion criteria
1. Has a known additional nonurothelial malignancy that is progressing or has
required active treatment within 3 years prior to study
randomization/allocation.
2. Has known active CNS metastases and/or carcinomatous meningitis.
3. Has known hypersensitivity to active substances or any of their excipients
including previous clinically significant hypersensitivity reaction to
treatment with pembrolizumab or other investigational agents being evaluated
within this study.
4. Has received prior systemic anticancer therapy including investigational
agents within 4 weeks before randomization/allocation.
5. Has an active infection requiring systemic therapy.
6. Has received prior radiotherapy within 2 weeks of first dose of study
intervention. Participants must have recovered from all radiation-related
toxicities, not require corticosteroids, and not have had radiation pneumonitis.
7. Has had major surgery (<3 weeks before first dose of study intervention).
8. Has received a live or live-attenuated vaccine within 30 days before the
first dose of study intervention. Administration of killed vaccines are allowed.
9. Is currently participating in or has participated in a study of an
investigational agent or has used an investigational device within 4 weeks
before the first dose of study intervention.
10. Has known history of human immunodeficiency virus (HIV; HIV 1/2 antibodies).
11. Has known history of hepatitis B (defined as HBsAg reactive) or known
hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
12. Has a history or has current evidence of any condition, therapy, or
laboratory abnormality that might confound the results of the study, interfere
with the participation for the full duration of the study, or is not in the
best interest of the participant to participate, in the opinion of the
treating investigator.
13. Has had an allogeneic tissue/solid organ transplant.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-506384-34-00 |
| EudraCT | EUCTR2020-004544-28-NL |
| Other | IND 152,554 |
| CCMO | NL82488.056.22 |