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Solid TumorPhase 1/2NCT07843550

A Phase 1/2 Trial Of Larotrectinib And Pembrolizumab In Patients With Solid Tumors Previously Treated With Immune Checkpoint Inhibitor Monotherapy

A Phase 1/2 study testing Larotrectinib and Pembrolizumab in people with Solid Tumor, run by M.D. Anderson Cancer Center at 1 site in United States.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

This is a single-center, open-label Phase 1/2 trial evaluating the safety and efficacy of the combination of larotrectinib and pembrolizumab in patients with advanced/metastatic lung adenocarcinoma or melanoma. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Tumor
What is being tested?
Larotrectinib and Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
1 siteUnited States
Study dates
1 Mar 2027to 13 Jul 2029
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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

  • Patients must meet all of the following inclusion criteria to be eligible for enrollment in the study.
  • Ability to understand and willingness to sign informed consent form prior to initiation of the study and any study procedures.
  • Capable of and willing to comply with scheduled visits, treatment plans, laboratory tests, and other study-related tests and procedures.
  • Age ≥18 years.
  • Histologically documented locally advanced or metastatic lung adenocarcinoma or melanoma.
  • Patients who have previously received ICI monotherapy:
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  • Must have a minimum drug exposure of at least 1 dose of ICI and documented disease progression on the treatment.
  • Patients must be willing to undergo tumor biopsy as required by the study, if safe and feasible.
  • Patients who are unable or unwilling to undergo pretreatment tumor biopsy may still be eligible for the study following discussion with the principal investigator (PI).
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Appendix 1) with no deterioration in performance status within 2 weeks prior to study treatment initiation.
  • Measurable disease per the RECIST v1.1 (Appendix 2).
  • Adequate organ function as defined below:
  • Hematologic Function: hematopoietic growth factors are not allowed ≤7 days prior to screening assessment for short-acting growth factors and ≤14 days prior to screening assessment for long-acting growth factors (i.e., half-life >48 hours [e.g., peg-filgrastim]):
  • Hemoglobin >9.0 g/dL (red blood cell/plasma transfusion is not allowed ≤14 days prior to screening assessment)
  • Absolute neutrophil count ≥1500/mL
  • Platelets ≥100,000/mL (platelet transfusion is not allowed ≤7 days prior to screening assessment)
  • Hepatic Function:
  • Total bilirubin <1.5 × ULN (<2.0 × ULN for patients with documented Gilbert's syndrome or <3.0 × ULN for patients for whom the indirect bilirubin level suggests an extrahepatic source of elevation)
  • AST/ALT ≤2.5 × institutional ULN. Transaminases up to 5 × ULN in the presence of liver metastases.
  • Serum albumin ≥2.5 g/dL.
  • Renal Function:
  • o Estimated glomerular filtration rate ≥60 mL/min by Modification of Diet in Renal Disease Formula or by 24-hour urine collection.
  • Coagulation:
  • Prothrombin time/international normalized ratio and activated partial thromboplastin time /partial thromboplastin time <1.5 × ULN, or within target range per institutional guidelines if taking anticoagulant(s), regardless of whether the anticoagulant use is prophylactic or therapeutic.
  • Life expectancy ≥3 months.
  • Able to swallow PO medications.
  • Larotrectinib and pembrolizumab can cause fetal harm when administered to a pregnant woman. For this reason, women of childbearing potential (WOCBP) must agree to use adequate contraception ((hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of the study treatment period, and for 4 months after completion of study treatment.
  • (Refer to Pregnancy Assessment Policy MD Anderson Cancer Center [MDACC] Institutional Policy # CLN1114). WOCBP includes all female patients, between the onset of menses (as early as 8 years of age) and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following:
  • Postmenopausal (no menses in ≥12 consecutive months)
  • History of hysterectomy or bilateral salpingo-oophorectomy
  • Ovarian failure (follicle-stimulating hormone and estradiol in menopausal range and have received whole pelvic radiation therapy)
  • History of bilateral tubal ligation or another surgical sterilization procedure • Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), intrauterine device, tubal ligation or hysterectomy, patient/partner post vasectomy, implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the duration of the study treatment period and the drug washout period is an acceptable practice; however, periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
  • Male patients must agree to use adequate contraception throughout the duration of the study treatment period and for 4 months after the last dose of study treatment.
  • WOCBP must have a negative blood pregnancy test within 14 days of study treatment initiation.

Who cannot join

  • Documented alterations in NTRK1, NTRK2, or NTRK3 including fusions, rearrangements, deletions, and single nucleotide variants by DNA sequencing or polymerase chain reaction test on circulating tumor DNA, fresh tumor biopsy, or archival tumor tissue (obtained within 3 years of first larotrectinib dose) performed in a Clinical Laboratory Improvement Amendments-certified or equivalent laboratory.
  • Patients who required dose interruption for more than 4 weeks, permanent discontinuation, or required systemic immunosuppression due to severe irAEs associated with previous ICI treatment.
  • Untreated CNS or leptomeningeal metastases. Patients with treated CNS metastases are allowed if ALL of the following conditions are met:
  • Radiation therapy ≥14 days prior to study treatment initiation
  • Surgical resection ≥28 days prior to study treatment initiation; no evidence of clinical or radiographic progression on CNS imaging ≤28 days prior to study treatment initiation
  • Residual neurological symptoms Grade ≤2 and on a stable dose of steroids and/or anticonvulsant therapy (if applicable) ≥14 days prior to study treatment initiation.
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  • Has other malignancy(ies) diagnosed or treated within 5 years of study treatment initiation except for:
  • Clinically insignificant tumors for which no systemic anticancer treatment is required (e.g., basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the breast or cervix)
  • Tumors that have been treated with curative intent with low risk for recurrence during trial participation. Note: Approval from the PI is required for exceptions.
  • Patients with known or suspected impairment of GI function including any conditions that might hinder drug absorption, the ability to take PO medication, other malabsorption, or uncontrolled inflammatory GI disease such as Crohn's disease or ulcerative colitis.
  • History of cerebrovascular stroke within 6 months of study treatment initiation.
  • History of interstitial lung disease (ILD) or non-infectious pneumonitis requiring high-dose glucocorticoids or any active ILD or pneumonitis, or prior thoracic radiotherapy within 2 months of enrollment.
  • Has any of the following cardiovascular abnormalities:
  • Medically uncontrolled hypertension (≥160 mmHg systolic blood pressure or ≥100 mmHg diastolic blood pressure based on an average of 3 readings)
  • Acute coronary syndrome (e.g., unstable angina, coronary artery stenting or angioplasty, bypass grafting) within 6 months prior to enrollment
  • History of uncontrolled clinically significant unstable arrhythmias. Patients who have pacemakers to control atrial arrhythmia are eligible for the study. Patients with medically controlled atrial fibrillation >1 month prior to study treatment initiation are eligible.
  • History of congenital long QT syndrome or prolonged corrected QT interval (QTc) using Fridericia's method >470 ms (unless a pacemaker is in place)
  • Left ventricular ejection fraction <50%
  • Symptomatic congestive heart failure (New York Heart Association Class II or higher).
  • Has active systemic infection requiring systemic therapy within 72 hours prior to study treatment initiation.
  • History of severe allergic reaction or known sensitivity to any of the study treatment components.
  • Patients who have had a major surgical procedure(s) ≤28 days or minor procedure(s) ≤7 days prior to study treatment initiation; in all cases, the patient must be sufficiently recovered and stable before study treatment initiation.
  • Has active severe acute respiratory syndrome coronavirus 2 infection. If symptomatic, the symptoms must have resolved prior to study treatment initiation.
  • Has active, untreated human immunodeficiency virus (HIV) infection (CD4+ T cell count ≤350 cells/μL and presence of acquired immunodeficiency syndrome [AIDS]-defining opportunistic infections in the past 12 months). For patients with CD4+ T cell counts >350 cells/μL or in the absence of AIDS-defining opportunistic infections, enrollment will be considered, if the following conditions are met:
  • Patient must be on an established antiretroviral therapy for at least 28 days prior to enrollment and treatment must not conflict with other study restrictions
  • Patient must have an HIV viral load less than 400 copies/mL prior to enrollment.
  • Has active/chronic hepatitis B or C virus infection (patients who are positive for hepatitis B surface antigen are excluded; patients who are positive for hepatitis B core antibody or hepatitis C antibody must have a negative hepatitis B DNA or hepatitis C RNA test result, respectively, before enrollment).
  • Has an active autoimmune disease, or ongoing any grade irAE from ICIs/other immunomodulatory treatments requiring systemic treatment (i.e., with use of disease modifying agents, non-physiologic doses of corticosteroids, or immunosuppressive drugs). Patients with autoimmune or ICI inhibitor/other immunomodulatory treatment-induced endocrine disorder on hormonal supplementation may be enrolled.
  • Any other unstable or clinically significant concurrent medical condition (including, but not limited to substance abuse, uncontrolled intercurrent illness including symptomatic arterial thrombosis, pulmonary embolism, etc.) that would, in the opinion of the investigator, jeopardize the safety of a patient, have an impact on their expected survival through the end of study participation, and/or affect their ability to comply with the requirements of the study.
  • Patients receiving specific oncologic therapies:
  • Prior therapy with any NTRK-targeted therapy
  • Treatment with targeted therapy, chemotherapy, or biologics/mAbs (nonimmunotherapy) ≤21 days or 5 half-lives (whichever is shorter) prior to study treatment initiation
  • Treatment with radiation therapy ≤14 days prior to study treatment initiation
  • Treatment with immunotherapy (e.g., ICIs) ≤28 days prior to study treatment initiation
  • Treatment with any other anticancer treatment not included in "a" through "d" ≤28 days prior to study treatment initiation
  • Treatment with any other investigational drug(s) not included in "a" through "e" ≤28 days prior to study treatment initiation (with the exception of provisionally approved mAb prophylaxis).
  • Patients who require treatment with systemic cyclosporin A or derivative.
  • Concomitant use of medications known to prolong QTc.
  • Concomitant use of medications that are sensitive or narrow therapeutic index substrates of cytochrome P450 (CYP) 3A, P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), or organic anion transporting polypeptide 1B3 (OATP1B3) during study treatment.
  • Concomitant use of medications known to be moderate or strong CYP3A4 or P-gp inhibitors and/or moderate or strong CYP3A4 inducers is prohibited within 7 days prior to study treatment initiation and during the study treatment period.
  • Pregnant or breastfeeding.
  • Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study treatment administration. Inhaled or topical steroids and adrenal replacement doses <10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Patients are permitted to use topical, ocular, intraarticular, intranasal, and inhalational corticosteroids (with minimal systemic absorption).
  • Patients who received a live, attenuated vaccine within 30 days prior to Cycle 1 Day 1.
  • Enrolled patients should not receive live vaccine during the study. Non-live COVID vaccines will be allowed on study, but it is recommended to avoid their use during the first treatment cycle (from 3 days prior to Cycle 1 Day 1 through Cycle 2 Day 3). Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines and are not allowed.
  • Unresolved toxicities from prior therapy (defined as having not resolved to Grade ≤1 or baseline) or any other toxicity that is deemed irreversible by the investigator. Exceptions include endocrinopathies from prior therapy or disease and successfully treated (such as hypothyroidism, diabetes mellitus), alopecia, vitiligo, and Grade ≤2 peripheral neuropathy.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

David Hong, MD contact

(713) 563-5844

dshong@mdanderson.org

United States1 site

  • UT MD Anderson

    Houston, Texas, 77030

    David Hong, MD, 713-563-5844, dshong@mdanderson.org

    David Hong, MD

Other trials in United States

About this study

This is a single-center, open-label Phase 1/2 trial evaluating the safety and efficacy of the combination of larotrectinib and pembrolizumab in patients with advanced/metastatic lung adenocarcinoma or melanoma.

Read the detailed description

Primary Objectives:

  • To determine the safety and tolerability of the larotrectinib and pembrolizumab combination in patients with advanced/metastatic lung adenocarcinoma or melanoma.
  • To determine the ORR of the larotrectinib and pembrolizumab combination in patients with advanced/metastatic lung adenocarcinoma or melanoma.

Secondary Objective:

  • To determine the DOR of the larotrectinib and pembrolizumab combination.

Exploratory Objective:

  • To evaluate blood and tissue-based pharmacodynamic biomarkers of the larotrectinib and pembrolizumab combination.
Conditions
Solid Tumor
Being tested
Larotrectinib, Pembrolizumab

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LarotrectinibDrug

    Also called Vitrakvi

    Taken twice daily

  • PembrolizumabDrug

    Also called Keytruda

    Give by IV infused over 30 minutes through an IV line containing a sterile 0.2 µm to 5 µm in-line or add-on filter.

Study groups in NCT07843550
Study groupRoleWhat they receive
Phase 1 and Phase 2: Treatment with Larotrectinib + PembrolizumabExperimentalLarotrectinib and pembrolizumab will be administered on an outpatient basis in 21-day cycles until disease progression, unacceptable toxicity, death, withdrawal of consent, or discontinuation from the study treatment for any other reason.
Receives: Drug: Larotrectinib; Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety and Adverse Events (AEs)

    Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

    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.

  1. First posted28 Sep 2026
  2. Study start1 Mar 2027 (estimated)
  3. Primary completion13 Jul 2027 (estimated)
  4. Study completion13 Jul 2029 (estimated)

Resources

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
22 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07843550
Sponsor's protocol ID
2026-0889
Other IDs
NCI-2026-07108
Status last verified
Sep 2026
First submitted
21 Sep 2026
Last updated
28 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Larotrectinib and Pembrolizumab in people with Solid Tumor, 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 34 inclusion and 45 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: opening soon, as of the sponsor's last update on 28 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact David Hong, MD ((713) 563-5844, dshong@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and Adverse Events (AEs) (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?

On the ClinicalTrials.gov record for NCT07843550.

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 28 Sep 2026.

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