Staggered, Chemo-Immunotherapy With Durvalumab, MEDI4736 Pemetrexed & Carboplatin (PC) for Metastatic Non-Squamous NSCLC

NCT04163432 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: HCI127115
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase II, open label, randomized study of durvalumab in combination with pemetrexed and carboplatin in eligible adult patients with locally advanced or metastatic non-small cell lung cancer. The study will focus on the efficacy of two alternative staggered dosing regimens.

Conditions

Non-Small Cell Lung Cancer Metastatic

Outcome Measures

Primary Outcomes (1)

• Clinical Benefit

  Clinical Benefit is the count of participants who have achieved a CR (Complete Response), PR (Partial Response), or SD (Stable Disease), assessed by RECIST 1.1 response criteria Response Evaluation Criteria in Solid Tumors (RECIST) is a standard measure of how well cancer patients respond to treatment. Possible scores are CR (total disappearance of all target lesions), PR (at least a 30% decrease of the sum of the longest diameter of all target lesions), PD (Progressive Disease; at least a 20% increase of the sum of the longest diameter of all target lesions), and SD (neither a sufficient decrease for PR, or sufficient increase for PD). This outcome measure will report the count of subjects who achieved any Clinical Benefit, Clinical Benefit for 3 months, and Clinical Benefit for 6 months.

  up to 11 months from the start of study treatment

Secondary Outcomes (4)

• Incidence of Adverse Events

  up to 5 years

• Objective Response

  up to 34 months from the start of study treatment

• Progression Free Survival (PFS)

  up to 5 years

• Overall Survival (OS)

  up to 5 years from the first dose of study drug

Study Arms (2)

Arm A: Chemo-Immuno

EXPERIMENTAL

ArmA receives chemotherapy on D1 and immunotherapy on D8 of a 28-day cycle for the first 2cycles. After the first 2cycles, patients on Arm A and Arm B will be administered chemotherapy and immunotherapy on D1 of a 21day cycle for cycles 3 and 4. After 4cycles of chemo-immunotherapy, patients receive maintenance therapy with durvalumab and pemetrexed until treatment discontinuation. Maintenance therapy is administered on D1 of a 21day cycle.

Drug: Durvalumab; Drug: Pemetrexed; Drug: Carboplatin

Arm B: Immuno-Chemo

EXPERIMENTAL

ArmB receives immunotherapy on D1 and chemotherapy on D8 of a 28-day cycle for the first 2cycles. After the first 2cycles, patients on Arm A and Arm B will be administered chemotherapy and immunotherapy on D1 of a 21day cycle for cycles 3 and 4. After 4cycles of chemo-immunotherapy, patients receive maintenance therapy with durvalumab and pemetrexed until treatment discontinuation. Maintenance therapy is administered on D1 of a 21day cycle.

Drug: Durvalumab; Drug: Pemetrexed; Drug: Carboplatin

Interventions

Pemetrexed DRUG

Pemetrexed dosing is adjusted for kidney function. Pemetrexed is dosed at 500mg/m2 for patients with a creatinine clearance ≥ 45 mL/min (by Cockcroft-Gault formula). If creatinine clearance is \< 45 mL/min, pemetrexed is dosed at 400 mg/m2.

Also known as: Alimta

Arm A: Chemo-Immuno; Arm B: Immuno-Chemo

Durvalumab DRUG

Durvalumab is administered at a dose of 1500mg for patients who weigh \>30 kg. If weight falls to ≤ 30 kg, weight-based dosing at 20mg/kg will be a utilized

Also known as: Imfinzi

Arm A: Chemo-Immuno; Arm B: Immuno-Chemo

Carboplatin DRUG

Carboplatin dosing is adjusted for kidney function.The total dose (in mg) of carboplatin will be calculated using the Calvert Formula utilizing a target AUC of 5 and a patient's GFR in mL/min.

Arm A: Chemo-Immuno; Arm B: Immuno-Chemo

Eligibility Criteria

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

You may qualify if:

• Male or female subject aged ≥ 18 years.
• Histologically or cytologically confirmed lung cancer.
• Metastatic non-squamous non-small cell lung cancer.
• Body weight \>30kg
• Patient has measurable disease as defined by RECIST 1.1 as assessed by either CT or MRI.
• Chemoimmunotherapy naïve (including durvalumab).
• ECOG Performance Status ≤ 2. --Note: If performance status = 2, ensure that there is a slot available prior to registration as only 20 PS = 2 patients will be enrolled on the protocol.
• Must have a life expectancy of at least 12 weeks.
• Adequate organ function as defined as:
• Hematologic:
• White blood cell count \> 2.0 g/dL
• Platelet count ≥ 100,000/mm3
• Hemoglobin ≥ 9 g/dL
• Absolute neutrophil count (ANC) ≥ 1,500/mm3
• Hepatic:

You may not qualify if:

• ALK or EGFR non-squamous non-small cell lung cancer.
• Prior radiation therapy within 2 weeks prior to cycle one day one.
• Exception: Prior palliative radiotherapy is permitted, provided it has been completed at least 2 days prior to study enrollment and no clinically significant toxicities are expected.
• Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP.
• Note: Local surgery of isolated lesions for palliative intent is acceptable.
• History of allogenic organ transplantation.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis,uveitis, etc\]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia
• Patients with endocrine disorders with controlled disease on hormone replacement therapy (e.g. adrenal, thyroid, or pituitary replacement therapy)
• Any chronic skin condition that does not require systemic therapy
• Patients without active disease in the last 5 years may be included but only after consultation with the principal investigator
• Patients with celiac disease controlled by diet alone
• Current or prior use of immunosuppressive medication within 14 days of cycle one day one, EXCEPT for the following permitted steroids:
• Intranasal, inhaled, topical steroids, eye drops or local steroid injection (eg,intra-articular injection);
• Systemic corticosteroids at physiologic doses ≤ 10mg/day of prednisone or equivalent;

Sponsors & Collaborators

• University of Utah: lead
• AstraZeneca: collaborator

Study Sites (1)

Huntsman Cancer Institute at University of Utah

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Interventions

durvalumab; Pemetrexed; Carboplatin

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Coordination Complexes; Organic Chemicals

Results Point of Contact

• Title: IIT Data Management Team
• Organization: Research Compliance Office, Huntsman Cancer Institute

IITDataManagement@hci.utah.edu

801-213-6215

Study Officials

• Matthew Gumbleton, MD

  Huntsman Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase II, open label, randomized study of durvalumab in combination with pemetrexed and carboplatin in eligible adult patients with locally advanced or metastatic non-small cell lung cancer.

Study Record Dates

• First Submitted: November 4, 2019
• First Posted: November 14, 2019
• Study Start: June 16, 2020
• Primary Completion: February 4, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: May 19, 2026
• Results First Posted: May 19, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)