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

NCT07843550 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2026-0889NCI-2026-07108
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (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

  Through study completion; an average of 1 year

Study Arms (1)

Phase 1 and Phase 2: Treatment with Larotrectinib + Pembrolizumab

EXPERIMENTAL

Larotrectinib 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.

Drug: Larotrectinib; Drug: Pembrolizumab

Interventions

Larotrectinib DRUG

Taken twice daily

Also known as: Vitrakvi

Phase 1 and Phase 2: Treatment with Larotrectinib + Pembrolizumab

Pembrolizumab DRUG

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.

Also known as: Keytruda

Phase 1 and Phase 2: Treatment with Larotrectinib + Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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)

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

UT MD Anderson

Houston, Texas, 77030, United States

Location

Related Links

• UT MD Anderson Website

MeSH Terms

Interventions

larotrectinib; pembrolizumab

Study Officials

• David Hong, MD

  UT MD Anderson

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David Hong, MD

CONTACT

(713) 563-5844; dshong@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2026
• First Posted: September 28, 2026
• Study Start (Estimated): March 1, 2027
• Primary Completion (Estimated): July 13, 2027
• Study Completion (Estimated): July 13, 2029
• Last Updated: September 28, 2026

Record last verified: 2026-09

Locations

US (1)