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)

  • STATUS
    Recruiting
  • End date
    May 2, 2026
  • participants needed
    230
  • sponsor
    AIO-Studien-gGmbH
Updated on 2 June 2022

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

Description

Patients without progression after two cycles of chemotherapy (induction treatment phase) will be randomized at a 1:1 ratio into one of 2 treatment arms (combination treatment phase). PD-L1 expression status will be evaluated based on available data. To better focus on patients with expected good clinical benefit from immunomodulating agents, only patients with checkpoint-inhibitor treatment as first-line monotherapy and a progression-free survival of at least 12 weeks will enter the study (at least two re-assessments after initiation of first-line treatment). Consequently, patients with disease progression as best response of first-line therapy cannot enter this study. Directly re-challenging patients with anti-PD-L1 and anti-CTLA agents after disease progression on checkpoint-inhibitor monotherapy will be avoided by the previous application of two cycles of platinum-based chemotherapy as induction treatment, which may also enhance the antigen release from tumor cells and may further support the subsequent immunotherapy.

Details
Condition NSCLC Stage IV
Treatment combination regimen tremelimumab /durvalumab, platinum-based chemotherapy (SoC)
Clinical Study IdentifierNCT05383001
SponsorAIO-Studien-gGmbH
Last Modified on2 June 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

• 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
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 Study Chair
Patients with celiac disease controlled by diet alone 14. Uncontrolled intercurrent
illness, including but not limited to, ongoing or active infection, symptomatic
congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac
arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions
associated with diarrhea, or psychiatric illness/social situations that would limit
compliance with study requirement, substantially increase risk of incurring AEs or
compromise the ability of the patient to give written informed consent 15. History of
another primary malignancy except
Malignancy treated with curative intent and with no known active disease ≥3 years
prior to study enrolment and of low potential risk for recurrence
Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of
disease
Adequately treated carcinoma in situ without evidence of disease 16. History of
leptomeningeal carcinomatosis 17. History of active primary immunodeficiency 18
Active infection including tuberculosis (clinical evaluation that includes clinical
history, physical examination and radiographic findings, and TB testing in line with
local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result)
hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients
with a past or resolved HBV infection (defined as the presence of hepatitis B core
antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for
hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative
for HCV RNA. 19. Receipt of live or live attenuated vaccine within 30 days prior to
the first dose of IP. Note: Patients should also not receive live or live attenuated
vaccine for the pertinent time frames during and after treatment defined in the
respective study drug's SmPC or IB
Known allergy or hypersensitivity to any of the study drugs or any of the study
drug excipients
Female patients who are pregnant or breastfeeding or male or female patients of
reproductive potential who are not willing to employ effective birth control from
screening to a defined timepoint after last dose of treatment (see Section 7.1 for
details) 22. A marked baseline prolongation of QT/QTc interval (e.g., repeated
demonstration of a QTc interval >450 ms); A history of additional risk factors for TdP
(e.g., heart failure, hypokalemia, family history of Long QT Syndrome)

Exclusion Criteria

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
Involvement in the planning and/or conduct of the study (applies to both sponsor staff
and/or staff at the study site) 5. Concurrent enrolment in another clinical study, unless
it is an observational (non-interventional) clinical study or during the follow-up period
of an interventional study 6. Treatment with any other investigational agent or
participation in another clinical study with therapeutic intent within 28 days prior to
randomization 7. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer
therapy (including second line platinum-based chemotherapy) with the exception of alopecia
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