TumorPhase 1NCT05273554
A Pilot Study to Assess Changes in Tumor Biology Following Second-line Treatment With Pembrolizumab Plus Lenvatinib in Patients With Advanced Pancreatic Ductal Adenocarcinoma
A Phase 1 study testing Pembrolizumab and lenvatinib in people with Tumor and Adenocarcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This is a clinical research study to learn if pembrolizumab in combination with lenvatinib can help to control pancreatic ductal adenocarcinoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tumor, Adenocarcinoma
- What is being tested?
- Pembrolizumab and lenvatinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Aug 2022to 22 Sep 2026
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- In order to be eligible for participation in this trial, the patient must:
- Have histologically or cytologically confirmed diagnosis of metastatic pancreatic adenocarcinoma based on pathology report
- Have received at least one prior regimen of therapy for metastatic disease. May have received an unlimited number of treatments in the neoadjuvant or adjuvant setting prior to the appearance of metastatic disease.
- Be willing and able to provide written informed consent for the trial.
- Be 18 years of age on day of signing informed consent.
- Have measurable disease based on RECIST 1.1. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
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- Have documented objective radiographic progression on or after stopping treatment with first-line therapy.
- Note: the same image acquisition and processing parameters should be used throughout the study for a given patient.
- Be willing to provide tissue from a newly obtained core- or excisional biopsy of a tumor lesion from a metastatic site. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Patients for whom newly-obtained samples cannot be provided (e.g. inaccessible or patient-safety concern) may submit an archived specimen only upon agreement from Merck. The specimen must be from a biopsy site that would be accessible for at least one subsequent biopsy after initiation on the trial.
- Has the ability to swallow and retain oral medication.
- Has adequately controlled BP with or without antihypertensive medications, defined as BP ≤150/90 mm Hg with no change in antihypertensive medications within 1 week prior to randomization
- Have a performance status of 0 or 1 on the ECOG performance status scale within 5 days of starting study treatment.
- Have a predicted life expectancy of greater than 3 months.
- Demonstrate adequate organ function as defined in Table 2. All screening labs should be performed within 10 days of treatment initiation.
- Male subjects are eligible to participate if they agree to the following during the intervention period and for at least 30 days after the last dose of lenvatinib
- Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR
- Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause [Appendix 5]) as detailed below:
- Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant. Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration.
- Please note that 30 days after lenvatinib is stopped, if the subject is on pembrolizumab only, no male contraception measures are needed.
- A female subject is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
- Is not a WOCBP OR
- Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), as described in Appendix 5 during the intervention period and for at least 120 days post pembrolizumab or 30 days post lenvatinib, whichever occurs last. The investigator should evaluate the potential for contraceptive method failure (i.e., noncompliance, recently initiated) in relationship to the first dose of study intervention
- A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention.
- If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the subject must be excluded from participation if the serum pregnancy result is positive.
- Additional requirements for pregnancy testing during and after study intervention are located in Appendix 5.
- The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
- Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Who cannot join
- Has pancreatic tumor other than adenocarcinoma, including: acinar cell carcinoma, pancreaticoblastoma, malignant cystic neoplasms, endocrine neoplasms, squamous cell carcinoma. Patients with vater-, periampullary duodenal-. or common bile duct malignancies are also excluded. Patients with mixed tumor types (adenocarcinoma plus other) may be included if a metastatic site has been documented as containing adenocarcinoma.
- Is currently receiving study therapy; or has participated in a study of an investigational agent and received study therapy, herbal/complementary oral- or IV medicine, or used an investigational device within 2 weeks of the first dose of this protocol's study treatment.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- Had a solid organ or hematologic transplant.
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Had a diagnoss of an additional malignancy made within 1 year prior to first dose of study treatment with the exception of curatively treated basal-cell carcinoma of the skin, squamous-cell carcinoma of the skin, localized prostate cancer, and/or curatively resected in situ cervical- and/or breast cancers.
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- Has presence of gastrointestinal condition, eg, malabsorption, that might affect the absorption of study drug.
- Has present or progressive accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment. The participant can receive diuretic drugs as needed per the treating physician, outside of the above-mentioned conditions.
- Has radiographically detectable (even if asymptomatic and/or previously treated) central nervous system metastases and/or carcinomatous meningitis as assessed by the investigator and with radiology review.
- Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug
- Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
- Has an active infection requiring systemic therapy.
- Has a history or current evidence of any condition, therapy (including dialysis), or laboratory abnormality that might confound the results of this trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient, in the opinion of the treating investigator.
- Has known psychiatric- or substance-abuse disorders that would interfere with cooperation with trial requirements.
- Has received prior therapy with lenvatinib, an anti-PD-1, anti-PD-L1, or anti PD-L2 agent, a VEGFR2 agent, or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137).
- Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
- Has known hepatitis B or hepatitis C
- Has received a live or live-attenuated vaccine within 30 days of planned start of study therapy (Cycle 1, Day 1). Administration of killed vaccines are allowed.
- Is unable to tolerate a contrast enhanced CT or MRI for staging/restaging purposes
- Has severe hypersensitivity (≥Grade 3) to pembrolizumab, lenvatinib, or any of its excipients.
- Has had a prior anti-cancer monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to such agents administered more than 4 weeks earlier.
- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered small molecule agent.
- Note: patients with ≤ Grade 2 neuropathy or alopecia are an exception to this criterion and may qualify for the study.
- Note: If patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study therapy.
- Has had major surgery within 3 weeks prior to first dose of study interventions. Note: Adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility
- Has preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula.
- Has urine protein ≥1 g/24 hours. Note: Participants with proteinuria ≥2+ (≥100 mg/dL) on urine dipstick testing (urinalysis) will undergo 24-hour urine collection for quantitative assessment of proteinuria.
- Has a left ventricular ejection fraction (LVEF) below the institutional (or local laboratory) normal range, as determined by multigated acquisition (MUGA) or echocardiogram (ECHO).
- Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation.
- NOTE: The degree of proximity to major blood vessels should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis following lenvatinib therapy.
- Has prolongation of QTcF interval to >480 ms.
- Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability.
- Note: Medically controlled arrhythmia would be permitted.
- Has a history of arterial thromboembolism within 12 months of start of study drug.
Trial locations and contacts
1 site in 1 country.
About this study
This is a clinical research study to learn if pembrolizumab in combination with lenvatinib can help to control pancreatic ductal adenocarcinoma.
Read the detailed description
Primary Efficacy Objective
Corresponding Endpoint To obtain a preliminary estimate of the ORR* of the combination of pembrolizumab and lenvatinib in patients with advanced pancreatic ductal adenocarcinoma ORR, defined by the proportion of participants who have a CR or PR as determined by RECIST version
Secondary Objective
Corresponding Endpoints
- Determine progression free survival (PFS) according to RECIST version 1.1 and iRECIST.
PFS defined as the time from enrollment to the first occurrence of disease progression or death from any cause, whichever occurs first
- To estimate DOR according to RECIST v1.1 and iRECIST.
- DOR defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first
- To estimate DCR using RECIST 1.1 and with confirmatory assessment as required by iRECIST at any time during the trial.
- DCR defined as the proportion of subjects who have a CR, PR, or SD
- To evaluate the efficacy, toxicity and survival following treatment with pembrolizumab and lenvatinib • OS defined as the time from the date of enrollment to the date of death due to any cause.
- Occurrence and severity of AEs, with severity determined according to NCI CTCAE,
Exploratory Objective
Corresponding Endpoints To identify molecular (genomic, metabolic, and/or proteomic) biomarkers that may be indicative of clinical response/resistance, safety, pharmacodynamic activity, and/or the mechanism of action of pembrolizumab and lenvatinib Molecular (genomic, metabolic and/or proteomic) determinants of response or resistance to treatments, using blood and/or tumor tissue
- Change in T-cell composition of tumor as identified by multiplex immunofluorescent assay of serial biopsies obtained from patients. Tumor infiltrate will be assessed for any change in response to this therapeutic approach.
- Additional measurements will include changes in immune composition of tumor stroma, T-cell receptor composition in infiltrating T cells, and serum cytokines. Tumor infiltrate and circulating cytokines will be assessed for change in response to these therapies.
- Conditions
- Tumor, Adenocarcinoma
- Being tested
- Pembrolizumab, lenvatinib
- Medical subject headings
- Neoplasms, Adenocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called KEYTRUDA®
Given by IV
lenvatinibDrug
Given by PO
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab | Experimental | by vein over about 30 minutes on Day 1 of each cycle. Receives: Drug: Pembrolizumab; Drug: lenvatinib |
| Lenvatinib | Experimental | 2 lenvatinib capsules at the same time by mouth every day while on study. Receives: Drug: Pembrolizumab; Drug: lenvatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
To obtain a preliminary estimate of the ORR* of the combination of pembrolizumab and lenvatinib in patients with advanced pancreatic ductal adenocarcinoma
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2022
- Study start31 Aug 2022
- Primary completion22 Sep 2026
- Study completion22 Sep 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for TumorStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Brandon Smaglo, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05273554
- Sponsor's protocol ID
- 2021-0274
- Other IDs
- NCI-2022-02033
- Status last verified
- Sep 2026
- First submitted
- 1 Mar 2022
- Last updated
- 29 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study to Assess Changes in Tumor Biology Following Second-line Treatment With Pembrolizumab Plus Lenvatinib in Patients With Advanced Pancreatic Ductal Adenocarcinoma
- ClinicalTrials.gov ID
- NCT05273554
- Acronym / sponsor ID
- 2021-0274
- Conditions
- Tumor, Adenocarcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 31 Aug 2022 (actual)
- Primary completion
- 22 Sep 2026 (actual)
- Study completion
- 22 Sep 2026 (actual)
- First posted
- 10 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a clinical research study to learn if pembrolizumab in combination with lenvatinib can help to control pancreatic ductal adenocarcinoma.
Detailed description
Primary Efficacy Objective
Corresponding Endpoint To obtain a preliminary estimate of the ORR* of the combination of pembrolizumab and lenvatinib in patients with advanced pancreatic ductal adenocarcinoma ORR, defined by the proportion of participants who have a CR or PR as determined by RECIST version
Secondary Objective
Corresponding Endpoints
- Determine progression free survival (PFS) according to RECIST version 1.1 and iRECIST.
PFS defined as the time from enrollment to the first occurrence of disease progression or death from any cause, whichever occurs first
- To estimate DOR according to RECIST v1.1 and iRECIST.
- DOR defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first
- To estimate DCR using RECIST 1.1 and with confirmatory assessment as required by iRECIST at any time during the trial.
- DCR defined as the proportion of subjects who have a CR, PR, or SD
- To evaluate the efficacy, toxicity and survival following treatment with pembrolizumab and lenvatinib • OS defined as the time from the date of enrollment to the date of death due to any cause.
- Occurrence and severity of AEs, with severity determined according to NCI CTCAE,
Exploratory Objective
Corresponding Endpoints To identify molecular (genomic, metabolic, and/or proteomic) biomarkers that may be indicative of clinical response/resistance, safety, pharmacodynamic activity, and/or the mechanism of action of pembrolizumab and lenvatinib Molecular (genomic, metabolic and/or proteomic) determinants of response or resistance to treatments, using blood and/or tumor tissue
- Change in T-cell composition of tumor as identified by multiplex immunofluorescent assay of serial biopsies obtained from patients. Tumor infiltrate will be assessed for any change in response to this therapeutic approach.
- Additional measurements will include changes in immune composition of tumor stroma, T-cell receptor composition in infiltrating T cells, and serum cytokines. Tumor infiltrate and circulating cytokines will be assessed for change in response to these therapies.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab | Experimental | Drug: Pembrolizumab, Drug: lenvatinibby vein over about 30 minutes on Day 1 of each cycle. |
| Lenvatinib | Experimental | Drug: Pembrolizumab, Drug: lenvatinib2 lenvatinib capsules at the same time by mouth every day while on study. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- Have histologically or cytologically confirmed diagnosis of metastatic pancreatic adenocarcinoma based on pathology report
- Have received at least one prior regimen of therapy for metastatic disease. May have received an unlimited number of treatments in the neoadjuvant or adjuvant setting prior to the appearance of metastatic disease.
- Be willing and able to provide written informed consent for the trial.
- Be 18 years of age on day of signing informed consent.
- Have measurable disease based on RECIST 1.1. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
Key exclusion criteria (34 listed)
- Has pancreatic tumor other than adenocarcinoma, including: acinar cell carcinoma, pancreaticoblastoma, malignant cystic neoplasms, endocrine neoplasms, squamous cell carcinoma. Patients with vater-, periampullary duodenal-. or common bile duct malignancies are also excluded. Patients with mixed tumor types (adenocarcinoma plus other) may be included if a metastatic site has been documented as containing adenocarcinoma.
- Is currently receiving study therapy; or has participated in a study of an investigational agent and received study therapy, herbal/complementary oral- or IV medicine, or used an investigational device within 2 weeks of the first dose of this protocol's study treatment.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- Had a solid organ or hematologic transplant.
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabAlso: KEYTRUDA®Given by IV | Drug | Lenvatinib, Pembrolizumab |
| lenvatinibGiven by PO | Drug | Lenvatinib, Pembrolizumab |
Primary outcome
To obtain a preliminary estimate of the ORR* of the combination of pembrolizumab and lenvatinib in patients with advanced pancreatic ductal adenocarcinoma
Time frame: through study completion, an average of 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2026.
- M D Anderson Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brandon Smaglo, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pembrolizumab and lenvatinib in people with Tumor and Adenocarcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 27 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To obtain a preliminary estimate of the ORR* of the combination of pembrolizumab and lenvatinib in patients with advanced pancreatic ductal adenocarcinoma (time frame: through study completion, an average of 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2026.