A Study of E7386 in Combination With Pembrolizumab in Previously Treated Participants With Selected Solid Tumors

• Status: Not yet recruiting
• Trial end date: 2024-05-24
• Target enrollment: 0
• Participant gender: All

Summary

The Phase 1b part of this study is conducted to assess the safety and tolerability of E7386 in combination with pembrolizumab in participants with previously treated selected solid tumors, and to determine the recommended Phase 2 dose (RP2D) of E7386 in combination with pembrolizumab.

The Phase 2 part of this study is conducted to assess the objective response rate (ORR) of E7386 in combination with pembrolizumab in participants with previously treated selected solid tumors (melanoma, colorectal cancer [CRC], hepatocellular carcinoma [HCC]) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Eisai Inc.
• Collaborator: Merck Sharp & Dohme Corp.
• Treatments: Pembrolizumab

Criteria

Inclusion Criteria

1. Male or female, age >=18 years at the time of informed consent

2. Have a histologically or cytologically-documented, advanced (metastatic and/or unresectable) selected solid tumor for which prior standard systemic therapy has failed. Selected tumor types: melanoma (excluding uveal melanoma), CRC, HCC

3. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

4. Must have disease progression on current or since the last anticancer treatment

5. At least one measurable lesion by computer tomography (CT) or magnetic imaging resonance (MRI) based on RECIST 1.1

6. Adequate organ function and serum mineral level per blood work

7. Melanoma cohort (Phase 2), participants must have:

• Unresectable Stage III or Stage IV melanoma, not amenable to local therapy.

• Received only 1 or, if known BRAF mut +ve, 2 lines of therapies prior to study enrollment and must have progressed on 1 prior BRAF inhibitor

8. CRC cohort (Phase 2), participants must have received at least 2 prior systemic therapies in adjuvant and/or metastatic setting (not exceeding 4 lines of therapies in the metastatic setting, progressed on at least 1 prior regimen in the metastatic setting or could not tolerate standard treatment)

9. HCC cohort (phase 2), participants must have:

• Barcelona Clinic Liver Cancer (BCLC) Stage B (not amenable for transarterial chemoembolization [TACE]) or Stage C and Child Pugh class A

• Has received only 1 prior line of systemic therapy in the locally advanced or metastatic setting, and must have progressed on treatment with an anti-PD-1/L1 monoclonal antibodies (mAb) administered either as monotherapy, or in combination

Exclusion Criteria

1. Prior treatment with E7386 or prior therapy with anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (example, CTLA-4, OX 40, CD137) that was discontinued due to a Grade 3 or higher immune-related (ir)AE

2. Participants with brain or subdural metastases, unless they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study

3. Any active infection requiring systemic treatment

4. Has severe hypersensitivity to study drugs and/or any of its excipients

5. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.

6. Has an active autoimmune disease that has required systemic treatment in the past 2 years

7. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis

8. Any bone disease/conditions as follows:

• Osteoporosis with T-score <-2.5 by DXA scan

• Metabolic bone disease, such as hyperparathyroidism, Paget's disease or osteomalacia

• Symptomatic hypercalcemia requiring bisphosphonate therapy

• History of any fracture within 6 months prior to starting study drug

• History of symptomatic vertebral fragility fracture or any fragility fracture

• Moderate or severe morphometric vertebral fracture at baseline.

• Any condition requiring orthopedic intervention.

• Bone metastases not being treated with a bisphosphonate or denosumab

9. Active viral hepatitis (B or C) as demonstrated by positive serology for participants with melanoma and CRC. Dual active hepatitis B virus (HBV) infection and hepatitis C virus (HCV) infection at study entry for participants with HCC

10. Known to be human immunodeficiency virus (HIV) positive

11. Received blood/platelet transfusion or G-CSF within 4 weeks before study entry

12. For Melanoma only, participants with ocular melanoma are excluded

13. For CRC only, participants are excluded if:

• has a tumor that is microsatellite instability high (MSI H)/ DNA mismatch repair-deficient (dMMR) positive

• has received prior treatment with anti-PD-1, anti-PD-L1, or anti-PD-L2 agent

14. For HCC only, participants are excluded if:

• clear invasion to bile duct or portal vein invasion of Vp4

• symptomatic gastric or esophageal varices per Investigator's clinical judgement

• history of hepatic encephalopathy within 6 months prior to starting study drug