Phase 2
Completed N=22
Ph1b/2 Dose-Escalation Study of Entinostat With Pembrolizumab in Non-small Cell Lung Cancer (NSCLC) With Expansion Cohorts in NSCLC, Melanoma, and Colorectal Cancer (CRC)
Non-Small Cell Lung Cancer · Melanoma · Mismatch Repair-Proficient Colorectal Cancer
Source: ClinicalTrials.gov NCT02437136 ↗
Enrolled (actual)
22
Serious AEs
44.0%
Results posted
Mar 2025
Primary outcomePrimary: Phase 2: Objective Response Rate (ORR), as Assessed Using Immune Response RECIST (irRECIST) — 22.2; 9.2; 18.9; 5.4 percentage of participants
Summary
The purpose of this study is to determine the safety and tolerability of entinostat used in combination with pembrolizumab in participants with NSCLC. Additionally, the purpose of the study is to assess how effective entinostat and pembrolizumab are in combination in participants with NSCLC, Melanoma, and Mismatch-Repair Proficient CRC.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Phase 2: Objective Response Rate (ORR), as Assessed Using Immune Response RECIST (irRECIST) |
22.2; 9.2; 18.9; 5.4 | — |
| SECONDARY Phase 2: Clinical Benefit Rate (CBR), as Assessed Using irRECIST |
33.3; 14.5; 35.8; 8.1 | — |
| SECONDARY Phase 2: CBR, as Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) |
22.2; 14.5; 30.2; 2.7 | — |
| SECONDARY Phase 2: Progression Free Survival (PFS), as Assessed Using irRECIST |
3; 17; 20; 3 | — |
| SECONDARY Phase 2: PFS, as Assessed Using RECIST 1.1 |
3; 17; 17; 2 | — |
| SECONDARY Phase 2: PFS Duration, as Determined by the Local Investigator Using irRECIST |
2.76; 2.83; 4.40; 1.91 | — |
| SECONDARY Phase 2: PFS Duration, as Determined by the Local Investigator Using RECIST 1.1 |
2.76; 2.69; 2.96; 1.91 | — |
| SECONDARY Phase 2: Overall Survival |
25.20; 11.73; 12.52; 9.79 | — |
| SECONDARY Phase 2: Duration of Response, as Assessed Using irRECIST |
15.61; 10.10; 25.49; 7.33 | — |
| SECONDARY Phase 2: Duration of Response, as Assessed Using RECIST 1.1 |
NA; 10.14; 25.49 | — |
| SECONDARY Phase 2: Time to Response, as Assessed Using irRECIST |
4.30; 2.83; 1.95; 4.17 | — |
| SECONDARY Phase 2: Time to Response, as Assessed Using RECIST 1.1 |
4.29; 2.83; 1.95 | — |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), AEs Resulting in the Permanent Discontinuation of Study Drug, and Death |
6; 7; 9; 18; 75; 53 | — |
| SECONDARY Phase 1b: Number of Participants With at Least One Dose Limiting Toxicities (DLTs) |
0; 1; 0 | — |
| SECONDARY Phase 1b: Recommended Phase 2 Dose (RP2D) |
5 | — |
Eligibility Criteria
Inclusion Criteria
Participants with NSCLC:
- Has histologically- or pathologically-confirmed recurrent/metastatic NSCLC.
- If has adenocarcinoma, required to have previously been tested for anaplastic lymphoma kinase (ALK) rearrangements and epidermal growth factor receptor (EGFR) mutations, with results available for collection in this study, and, if positive, has been treated with prior epidermal growth factor receptor (EGFR) or ALK therapy.
- Received at least 1 chemotherapeutic regimen in the advanced/metastatic setting and experienced documented, unequivocal progressive disease by either RECIST 1.1 or clinical assessment. Additional requirements related to prior treatments applied and may have been dependent on mutational status.
- Participants with NSCLC enrolled in Cohort 1 of the Expansion Phase should not have been previously treated with a PD-1/PD-L1-blocking antibody.
Participants in Expansion Phase, Cohorts 2 (NSCLC) and 3 (Melanoma):
- Previously treated with a PD-1/PD-L1-blocking antibody and experienced documented, unequivocal radiographic progression of disease by irRECIST, or similar criteria during or within 12 weeks after last dose of such treatment. Participants must have received at least 6 weeks of PD-1/PD-L1 therapy for Cohort 2 and at least 8 weeks of PD-1/PD-L1 therapy for Cohort 3.
Participants with Melanoma:
- In addition to having been previously treated with a PD-1/PD-L1-blocking antibody, has a histologically- or cytologically-confirmed diagnosis of unresectable or metastatic melanoma and experienced unequivocal progressive disease during treatment with a Serine/threonine-protein kinase B-Raf (BRAF) inhibitor if BRAF V600 mutation-positive. Treatment with BRAF inhibitor may occur after treatment with the checkpoint inhibitor.
Participants in Expansion Phase, Cohort 4 (CRC):
- Received at least 1 chemotherapeutic regimen in the advanced/metastatic setting and experienced documented, unequivocal progressive disease by either RECIST 1.1 or clinical assessment. Must have documented mismatch repair-proficient colon cancer as determined by either immunohistochemistry for mismatch repair proteins or polymerase chain reaction (PCR)-based functional microsatellite instability. Participants with CRC enrolled in Cohort 4 should not have been previously treated with a PD-1/PD-L1-blocking antibody (that is, pembrolizumab, nivolumab, MEDI4736, or GNE PDL1 [MPDL3280A]).
All Participants:
- Aged 18 years or older on the day written informed consent is given.
- If has brain metastases, must have stable neurologic status following local therapy for at least 4 weeks without the use of steroids or on stable or decreasing dose of ≤10 milligrams (mg) daily prednisone (or equivalent), and must be without neurologic dysfunction that would confound the evaluation of neurologic and other AEs.
- Evidence of locally recurrent or metastatic disease based on imaging studies within 28 days before the first study drug dose:
- At least 1 measurable lesion ≥20 mm by conventional techniques or ≥10 mm by spiral computed tomography (CT) scan or magnetic resonance imaging (MRI), with the last imaging performed within 28 days before the first study drug dose. If there is only 1 measurable lesion and it is located in previously irradiated field, it must have demonstrated unequivocal progression according to RECIST, version 1.1.
- If receiving radiation therapy, has a 2-week washout period following completion of the treatment prior to receiving the first study drug dose and continues to have at least 1 measurable lesion, per above criterion.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Has acceptable renal and hepatic function and stable hematologic and coagulation status.
- Female participants must not be pregnant. If a participants is of childbearing potential, the participant must agree to use effective contraception, as defined in the protocol, during the study and for 120 d
Data sourced from ClinicalTrials.gov (NCT02437136). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.