Pembrolizumab plus single-agent chemotherapy as first-line treatment for advanced non-small cell lung cancer in patients with ECOG performance status 2

A Pilot Study of Pembrolizumab and Single Agent Chemotherapy as First Line Treatment for Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer With Eastern Cooperative Oncology Group (ECOG) Performance Status of 2

This trial will try pembrolizumab with one chemotherapy drug as first treatment to see if it is tolerable and helps people with advanced non-small cell lung cancer who have an ECOG performance status of 2.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 28 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Rochester (other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation, prednisone, pembrolizumab
• Locations: 2 sites (Rochester, New York and 1 other locations)
• Trial ID: NCT04297605 on ClinicalTrials.gov

What this trial studies

This is a Phase 1, first-line combination trial enrolling adults with histologically confirmed stage IIIc or IV non-small cell lung cancer who have an ECOG performance status of 2. Participants receive pembrolizumab together with a single chemotherapy agent (options include pemetrexed or nab-paclitaxel) and are followed for safety, tolerability, and early signs of anti-tumor activity. Eligibility requires basic blood and kidney function thresholds and allows small, asymptomatic brain metastases. The design aims to define whether this combination can be delivered safely to patients who are not candidates for standard platinum-doublet therapy.

Who should consider this trial

Good fit: Adults (over 18) with histologically confirmed non-small cell lung cancer, ECOG PS 2, clinical stage IIIc (who are ineligible for or refuse chemoradiation) or stage IV (for whom platinum doublet is inappropriate or declined), with required laboratory values and willingness to use contraception if applicable are the intended participants.

Not a fit: Patients with better performance status (ECOG 0–1) who are eligible for standard platinum-doublet therapy, those with active or symptomatic brain metastases, significant organ dysfunction, or who are pregnant are unlikely to be appropriate or benefit from this trial.

Why it matters

Potential benefit: If successful, this combination could provide a tolerable first-line option that improves symptoms or clinical outcomes for patients with advanced NSCLC and limited performance status.

How similar studies have performed: Pembrolizumab combined with chemotherapy has shown clear benefit in fitter NSCLC populations, but its safety and effectiveness specifically in ECOG PS2 patients remain less well established.

Eligibility criteria

Inclusion Criteria:

1. Participants must be \>18 years old at time of diagnosis
2. Histologically confirmed non-small cell lung cancer
3. ECOG PS 2
4. Clinical staging of IIIc or IV disease.

4A. For patients with stage IIIc disease, patients are ineligible for or refuse standard treatment with platinum-double chemotherapy and radiation.

4B. For patients with stage IV disease, platinum doublet chemotherapy is not appropriate, deemed unsafe by the treating physician, or declined by the patient

4C. Screening lab work must meet the following parameters:

4Ca. Absolute neutrophil count (ANC) ≥1000/mm3

4Cb. Platelet count ≥100,000/mm3

4Cc. CrCl\>50 (if pemetrexed is to be offered)

4Cd. AST and ALT ≤ 2.5 x ULN

4D. Patients with small, asymptomatic brain metastases are eligible

4E. Women of childbearing potential must be negative for pregnancy testing (urine or blood) and agree to use effective contraception. Viable contraception should be used after trial screening, before initiation of chemotherapy, and throughout the duration of active treatment in the study.

Non-childbearing potential is defined as (by other than medical reasons): -Amenorrheic \>2 years

* Amenorrheic for \<2 years and a follicle-stimulating hormone value in the postmenopausal range upon pre-study (screening) evaluation
* Post hysterectomy, oophorectomy or tubal ligation. Otherwise the patient must be willing to use 2 adequate barrier methods throughout the study, starting with the screening visit through 120 days after the last dose of study drug

  4F.Participants must read or be read and explained the purposes of the study and sign a statement of informed consent prior to participation. Those who do not read or understand English are eligible and may be consented according to institutional regulations.

Exclusion Criteria:

1. Patients with history of autoimmune conditions with the following exceptions, which are allowed: alopecia, vitiligo, rheumatoid arthritis, psoriasis/psoriatic arthritis, Hashimoto's thyroiditis
2. Patients on immunosuppressive medication, including steroids (if doses exceed equivalent of prednisone 10 mg daily). Short courses of steroids which are discontinued prior to start of treatment are acceptable.
3. Patients with cardiovascular, hepatic, or renal systemic diseases that would preclude use of chemotherapy and/or immunotherapy per the treating investigator.
4. The patient must not be on any clinical trials involving other experimental therapies during study treatment
5. Women who are currently pregnant or breast-feeding
6. Patients with any other concurrent medical or psychiatric condition that were deemed inappropriate for entry into the study per the investigator.
7. Symptomatic, untreated brain metastases. Patients with treated brain metastases may be considered eligible after completion of radiation if steroids have been tapered to less than equivalent of 10 mg of prednisone.
8. Active infection requiring IV antibiotics

Where this trial is running

Rochester, New York and 1 other locations

• University of Rochester — Rochester, New York, United States (NOT_YET_RECRUITING)
• University of Rochester — Rochester, New York, United States (RECRUITING)

Study contacts

• Principal investigator: Megan Baumgart — University of Rochester
• Study coordinator: Megan Baumgart

Conditions: Non-small Cell Lung Cancer, Eastern Cooperative Oncology Group, pembrolizumab, performance status of 2