Randomized Phase II, Open-label Efficacy and Safety Study of Second-line Durvalumab Plus Tremelimumab Versus Platinum-based Chemotherapy Alone in Patients With NSCLC and First-line Checkpoint-inhibitor Therapy (Re-Check)

NCT05383001 | Withdrawn Phase 2

• 3 other identifiers: AIO-TRK-02212017-003780-35ESR-17-12719
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label, randomized, Phase II multicenter study designed to evaluate the safety and efficacy of two different second-line strategies: After failure of first line mono-immunotherapy with checkpoint inhibitors (anti-PD-1/PD-L1), and subsequent 2 cycles of standard of care platinum-based chemotherapy, 2 treatment arms will be compared: Arm A (Experimental Arm): After randomization, patients will receive a combination regimen featuring a single, priming dose of tremelimumab together with conventional durvalumab dosing. Durvalumab maintenance therapy will subsequently be continued as study treatment for up to 12 cycles. Arm B: After randomization, patients will continue to receive another 2-4 cycles of platinum-based chemotherapy. Afterwards, patients will end treatment or receive maintenance pemetrexed therapy as per marketing authorization (depending on histology, maximum of 13 cycles) at the discretion of the investigator

Conditions

NSCLC Stage IV

Outcome Measures

Primary Outcomes (1)

• PFS1

  Progression-free survival 1 using Investigator assessments according to RECIST 1.1, defined as the time from randomization in the study until objective tumor progression and do not include deaths

  49 months

Secondary Outcomes (8)

• PFS2

  49 months

• OS

  49 months

• ORR

  49 months

• Subgroup analysis

  49 months

• DoR

  49 months

Study Arms (2)

Arm A: tremelimumab /durvalumab (1 cycle), subsequently Durvalumab maintenance therapy

EXPERIMENTAL

Drug: combination regimen tremelimumab /durvalumab

Arm B: platinum-based chemotherapy (SoC)

OTHER

Drug: platinum-based chemotherapy (SoC)

Interventions

combination regimen tremelimumab /durvalumab DRUG

Induction treatment: 2 cyles of Q3W second-line plantium-based chemotherapy according to standard of care: Cisplatin or carboplatin in combination with pemetrexed, paclitaxel, nab-paclitaxel, vinorelbine or gemcitabine Combination treatment: Durvalumab 1500 mg fixed dose plus tremelimumab 300 mg fixed bolus dose Maintenance Therapy: Durvalumab 1500 mg fixed dose Q4W up to 12 cycles within the study

Arm A: tremelimumab /durvalumab (1 cycle), subsequently Durvalumab maintenance therapy

platinum-based chemotherapy (SoC) DRUG

Induction treatment: 2 cyles of Q3W second-line plantium-based chemotherapy according to standard of care: Cisplatin or carboplatin in combination with pemetrexed, paclitaxel, nab-paclitaxel, vinorelbine or gemcitabine Combination treatment: Continuation of second-line chemotherapy with 2-4 further cycles (Q3W) platinum-based combination therapy. Maintenance Therapy: Optional continued maintenance therapy with pemetrexed according to marketing authorization will be allowed for a maximum of 13 cycles.

Arm B: platinum-based chemotherapy (SoC)

Eligibility Criteria

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

You may qualify if:

• Signed Informed Consent Form
• Age \>18 years at time of study entry
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Histologically or cytologically confirmed, stage IV NSCLC (per the Union Internationale contre le Cancer/American Joint Committee on Cancer staging system).
• Indication for standard-of-care second line platinum-based chemotherapy, using cisplatin or carboplatin in combination with pemetrexed, paclitaxel, nab-paclitaxel, vinorelbine or gemcitabine
• Life expectancy of \> 12 weeks
• Body weight \> 30 kg
• First-line mono-immunotherapy with checkpoint inhibitors (anti-PD1/PD-L1) with a best response of stable disease (SD) or better
• Documented tumor PD-L1 expression status of ≥50%. Any existing data can be used.
• First-line progression-free survival of at least 12 weeks after at least two re-assessments after initiation of first-line treatment.
• Patients who have received prior neo-adjuvant, adjuvant chemotherapy, or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment-free interval of at least 6 months from initiation of first-line immunotherapy since the last adjuvant chemotherapy or chemoradiotherapy cycle.
• Patients with a history of treated asymptomatic CNS metastases are eligible, provided they meet all of the following criteria:
• No ongoing requirement for corticosteroids as therapy for CNS disease
• No stereotactic radiation within 7 days or whole-brain radiation within 14 days prior to enrolment
• No evidence of interim progression between the completion of CNS-directed therapy and the screening

You may not qualify if:

• \. Use of immunosuppressive medication (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and antitumor necrosis factor \[anti-TNF\] agents) within 14 days prior to randomization. The following are exceptions to this criterion:
• Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be eligible after discussion with the study chair.
• The use of inhaled corticosteroids for chronic obstructive pulmonary disease, mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension, and low-dose supplemental corticosteroids for adrenocortical insufficiency are allowed.
• Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
• Systemic corticosteroids at physiologic doses not exceeding 10 mg/day of prednisone or its equivalent
• Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
• Prior treatment with other immune-modulating agents (other than anti-PD-1/PD-L1) 3. Treatment with systemic immunostimulatory agents (including but not limited to IFNs, IL-2) within 4 weeks or five half-lives of the drug, whichever is longer, prior to randomization. Prior treatment with cancer vaccines is allowed.
• Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Chair.
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the Study Chair.
• \. Any toxicity that led to permanent discontinuation of prior immunotherapy. 9. A ≥ grade 4 immune related AE or an immune related neurologic or ocular AE of any grade while receiving prior immunotherapy.
• \. Any concurrent chemotherapy, investigational product, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
• \. History of allogenic organ transplantation. 12. 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.
• \. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement

Sponsors & Collaborators

• AIO-Studien-gGmbH: lead
• AstraZeneca: collaborator

Study Sites (1)

Asklepios Fachkliniken München-Gauting

Gauting, 82131, Germany

Location

Related Links

• AIO - Working Group for Medical Oncology from the German Cancer Society

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

durvalumab; Platinum Compounds

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Inorganic Chemicals

Study Officials

• Niels Reinmuth, Prof. Dr.

  Asklepios Fachkliniken München-Gauting, Thorakale Onkologie

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: May 17, 2022
• First Posted: May 19, 2022
• Study Start: May 20, 2022
• Primary Completion: May 1, 2026
• Study Completion: May 1, 2026
• Last Updated: September 27, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)