Phase 1 Trial of MK-2870 as Monotherapy and in Combination with Pembrolizumab in Subjects with Advanced Solid Tumors

JRCT ID: jRCT2031230356

Registered date:22/09/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Solid tumors (Arm 1), NSCLC (Arm 2 and Arm 3)
• Date of first enrollment: 26/10/2023
• Target sample size: 48
• Study type: Interventional

Intervention(s)

[Arm 1] Each cycle will be a 2 week, MK-2870 2, 4, 5 mg/kg will be administered as a 90 minute (+-15 minutes) IV infusion every 2 weeks (Q2W).
[Arm 2] Each cycle will be a 6 week, Pembrolizumab 400 mg will be administered as a 30 minute IV infusion every 6 weeks (Q6W). MK-2870 2, 4, 5 mg/kg will be administered as a 90 minute (+-15 minutes) IV infusion every 2 weeks (Q2W).
[Arm 3] Each cycle will be a 6 week, Pembrolizumab 400 mg will be administered as a 30 minute IV infusion every 6 weeks (Q6W). MK-2870 2, 4 mg/kg will be administered as a 90 minute (+-15 minutes) IV infusion every 2 weeks (Q2W). Carboplatin (AUC 5 mg/mL/min) will be administered as an IV infusion over approximately 60 minutes every 3 weeks (Q3W).

Outcome(s)

Primary Outcome

Safety and tolerability
Objective response rate (ORR)

Secondary Outcome

The PK profile of MK-2870 and pembrolizumab (only Arm 2 and 3)
The incidence of ADA formation to MK-2870 and pembrolizumab
Objective response rate (ORR) and Duration of Response (DOR)

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

- [Arm 1] Histologically or cytologically confirmed advanced/metastatic solid tumor by pathology report and have received, or been intolerant to, all treatment known to confer clinical benefit.
- [Arm 2 and Arm 3] Have a histologically or cytologically confirmed diagnosis of advanced or metastatic NSCLC.
- [Arm 2 and Arm 3] Confirmation that EGFR-, ALK-, or ROS1-directed therapy is not indicated as primary therapy.
- [Arm 2 only] Has tumor tissue that demonstrates PD-L1 TPS >=50% as determined by PD-L1 IHC 22C3 pharmDx assay by local laboratory.
- [Arm 1 only] Participants who have AEs due to previous anticancer therapies must have recovered to <= Grade 1 or baseline.
- Archival tumor tissue sample or newly obtained core or incisional biopsy of a tumor lesion not previously irradiated has been provided.
- Have an ECOG performance status of 0 or 1 within 3 days before the start of study intervention.

Exclude criteria

- Has symptomatic ascites or pleural effusion.
- Has Grade >=2 peripheral neuropathy.
- Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or corneal disease that prevents/delays corneal healing.
- Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease.
- Has uncontrolled, significant cardiovascular disease or cerebrovascular disease including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of QTcF interval to >480 ms, and/or other serious cardiovascular and cerebrovascular diseases within the 6 months preceding study intervention.
- Received prior treatment with a TROP2-targeted ADC.
- Received prior treatment with a topoisomerase I-containing ADC.
- [Arm 1 only] Has received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher irAE or was discontinued from that treatment due to Grade 2 myocarditis or recurrent Grade 2 pneumonitis.
- [Arm 2 and Arm 3] Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor.
- [Arm 2 and Arm 3] Has received prior systemic chemotherapy or other targeted or biological antineoplastic therapy for their advanced or metastatic NSCLC.
- [Arm 2 and Arm 3] Has received radiation therapy to the lung that is >30 Gy within 6 months of the first dose of study intervention.
- Received prior systemic anticancer therapy including investigational agents within 4 weeks before allocation.
- Received prior radiotherapy within 2 weeks of start of study intervention, or radiation-related toxicities, requiring corticosteroids.
- Requires treatment with a strong inhibitor or inducer of CYP3A4 at least 14 days before the first dose of study intervention and throughout the study.
- Received colony-stimulating factors within 14 days prior to the first dose of study intervention.
- [Arm 2 and Arm 3] Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication.
- [Arm 2 and Arm 3] Active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy.
- Known additional malignancy that is progressing or has required active treatment within the past 3 years.
- Known active CNS metastases and/or carcinomatous meningitis.
- History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- Active infection requiring systemic therapy.
- History of HIV infection. HIV testing is not required.
- Concurrent active Hepatitis B and Hepatitis C virus infection.
- History of allogeneic tissue/solid organ transplant.

Related Information

• Primary Sponsor: Koh Yasuhiro