Tarlatamab + Durvalumab for Lung Cancer
(DeLLphi-305 Trial)
Recruiting in Palo Alto (17 mi)
+217 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Amgen
Must be taking: Platinum-etoposide, Durvalumab
Must not be taking: Corticosteroids, Immunosuppressants
Disqualifiers: CNS metastases, Autoimmune disorders, others
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?The primary objective of this study is to compare the efficacy of tarlatamab plus durvalumab with durvalumab alone on prolonging overall survival (OS).
Will I have to stop taking my current medications?
The trial does not specify if you must stop taking your current medications, but you cannot be on systemic corticosteroids or other immunosuppressive therapy within 14 days before starting the study treatment. It's best to discuss your specific medications with the study team.
What safety information is available for the combination of Tarlatamab and Durvalumab in lung cancer treatment?
Durvalumab, used in various cancer treatments, has shown some safety concerns, including immune-related side effects like pneumonitis (lung inflammation), colitis (inflammation of the colon), and thyroid issues. In studies, most side effects were mild, but some serious cases, including treatment-related deaths, were reported. The combination with other drugs like tremelimumab increased the risk of severe side effects.
12345What makes the drug combination of Tarlatamab and Durvalumab unique for lung cancer treatment?
The combination of Tarlatamab and Durvalumab is unique because it involves using two immune-based therapies together, where Durvalumab is an anti-PD-L1 inhibitor that helps the immune system attack cancer cells, and Tarlatamab is a novel agent that may enhance this effect. This approach aims to improve outcomes in lung cancer by leveraging the body's immune response more effectively than traditional treatments.
26789Eligibility Criteria
This trial is for adults with extensive-stage small-cell lung cancer who've had 3-4 cycles of specific chemo and a drug called durvalumab without their disease getting worse. They should be expected to live at least 12 more weeks, have resolved treatment side effects (except hair loss or tiredness), and good organ function. People with active brain metastases or poor physical status can't join.Inclusion Criteria
You are expected to live for at least 12 more weeks.
Criterion: You are not allowed to participate.
You have agreed to take part in the study before it starts.
+7 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive tarlatamab every 2 weeks and durvalumab every 4 weeks, or durvalumab alone every 4 weeks
Until disease progression or unacceptable toxicity
Bi-weekly and monthly visits
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study aims to see if adding tarlatamab to durvalumab improves overall survival compared to using durvalumab alone in patients who have already received initial treatments for extensive-stage small-cell lung cancer.
2Treatment groups
Experimental Treatment
Active Control
Group I: Tarlatamab in Combination With DurvalumabExperimental Treatment2 Interventions
Participants will receive tarlatamab once every 2 weeks (Q2W) and durvalumab once every 4 weeks (Q4W).
Group II: Durvalumab AloneActive Control1 Intervention
Participants will receive durvalumab Q4W alone.
Durvalumab is already approved in European Union, United States, Japan for the following indications:
🇪🇺 Approved in European Union as Imfinzi for:
- Locally advanced, unresectable non-small cell lung cancer (NSCLC)
🇺🇸 Approved in United States as Imfinzi for:
- Extensive-stage small cell lung cancer (ES-SCLC)
- Limited-stage small cell lung cancer (LS-SCLC)
- Locally advanced or metastatic urothelial carcinoma
🇯🇵 Approved in Japan as Imfinzi for:
- Not specified in provided sources
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Montefiore Medical Center - BronxBronx, NY
Oncology Hematology Care IncorporatedCincinnati, OH
Sarah Cannon Research InstituteNashville, TN
US Oncology Research Investigational Products CenterIrving, TX
More Trial Locations
Loading ...
Who Is Running the Clinical Trial?
AmgenLead Sponsor
References
Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [2022]The prominent immune checkpoint molecule, programmed cell death ligand-1 (PD-L1), is the object of increasing attention. Here, we report a meta-analysis investigating the safety and efficacy of durvalumab (MEDI4736), an inhibitor of PD-L1, in various solid tumors.
A phase IB study of durvalumab with or without tremelimumab and platinum-doublet chemotherapy in advanced solid tumours: Canadian Cancer Trials Group Study IND226. [2021]This multicenter phase Ib study aimed to establish a recommended phase II dose for durvalumab (Du) ± tremelimumab (Tr) in combination with standard platinum-doublet chemotherapy. Eligible patients were enrolled into one of six dose levels (DL) of Du ± Tr which included concomitant treatment with standard platinum-doublet regimens; (pemetrexed, gemcitabine, etoposide, (each with cisplatin or carboplatin) or nab-paclitaxel (with carboplatin)). Dose escalation was according to a Rolling Six type design. Both weight-based and fixed dosing of Du and Tr were explored. Du was continued until progression. Tr dosing was finite (up to 6 doses) with increasing dose and/or frequency by DL. 136 patients were enrolled. The majority of drug-related adverse events (AEs) were ≤ grade 2 and attributable to chemotherapy. AEs considered related to immunotherapy were mainly ≤ grade 2; the most frequent (occurring ≥10 %) were colitis/diarrhea, skin, and thyroid dysfunction. Seven patients had DLTs including pneumonitis, myocarditis, diarrhea, encephalitis, motor neuropathy, and enterocolitis. There were 2 treatment-related deaths. Tr and Du exposures did not appear affected by chemotherapy. Among the 73 non-small cell lung cancer (NSCLC) patients treated, the objective response rate was 51 % (95 %CI = 38.7-62.6 %) with a median progression-free and overall survival of 6.5 months (95 % CI = 5.5-9.4 months) and 19.8 months (95 % CI = 14.8 months - not yet reached) respectively. Anti-tumour activity was observed across PD-L1 subtypes. Du 1500 mg q3w and Tr 75 mg q3wx5 can be safely combined with platinum-doublet chemotherapy. Efficacy among NSCLC patients appears comparable to results from other immunotherapy and chemotherapy combination trials. NCT02537418.
Characterizing immune-mediated adverse events with durvalumab in patients with unresectable stage III NSCLC: A post-hoc analysis of the PACIFIC trial. [2022]Immune-mediated adverse events (imAEs), including all-cause immune-mediated pneumonitis, were reported in approximately 25% of patients in the placebo-controlled, phase III PACIFIC trial of durvalumab monotherapy (for up to 12 months) in patients with unresectable, stage III NSCLC and no disease progression after concurrent chemoradiotherapy; only 3.4% of patients experienced grade 3/4 imAEs. With broad application of the PACIFIC regimen (consolidation durvalumab after chemoradiotherapy), now standard-of-care in this setting, there is a need to better characterize the occurrence of imAEs with this regimen.
Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis. [2023]Background: Recently, the combination of durvalumab and tremelimumab, two immune checkpoint inhibitors, for the treatment of different types of cancers has been considered; however, its overall effects, including its safety, are still unclear and need to be further investigated. Objectives: The aim of the present systematic review and meta-analysis was to investigate the safety and tolerability of this combination of drugs. Methods: A systematic review of the literature, based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement, was conducted by employing online electronic databases and the American Society of Clinical Oncology (ASCO) Meeting Library. The selection of eligible publications was made following a staged screening and selection process. The software RevMan 5.4 was used to run the quantitative analysis and forest plots, while the Cochrane tool was employed for risk of bias assessment. Results: From the retrieved 157 results, 9 randomized controlled trials involving 3060 patients were included. By comparing the combination of durvalumab and tremelimumab vs. durvalumab monotherapy, it was observed that: adverse events (AEs) ≥ Grade 3 incidence was 32.6% (536/1646) vs. 23.8% (336/1414) (Z = 2.80; p = 0.005; risk ratio (RR) = 1.44), reduced appetite incidence was 10.8% (154/1427) vs. 8.3% (108/1305) (Z = 2.26; p = 0.02; RR = 1.31), diarrhea was reported in 15.6% (229/1473) vs. 8.1% (110/1352) (Z = 5.90; p
Real-World Incidence of Pneumonitis in Patients Receiving Durvalumab. [2022]Durvalumab is a programmed cell death ligand 1 (PD-L1) inhibitor indicated for stage III, unresectable non-small cell lung cancer (NSCLC) consolidation therapy following concurrent platinum-based chemoradiation based on results of the PACIFIC trial. Safety data of durvalumab demonstrates an increased risk of immune-related adverse effects (irAEs), most notably pneumonitis. Pneumonitis is a serious and potentially fatal complication of immunotherapy. It is important to investigate the incidence of pneumonitis in clinical practice to evaluate the generalizability of published data. The objective of this study is to assess and characterize real-world incidence of pneumonitis in patients with NSCLC receiving durvalumab.
Tumor PD-L1 expression is associated with outcomes in stage III non-small cell lung cancer (NSCLC) patients treated with consolidation durvalumab. [2022]Durvalumab is an anti-PD-L1 immune checkpoint inhibitor approved for consolidation therapy for patients with stage III non-small cell lung cancer (NSCLC) after chemoradiation. The purpose of our study was to evaluate the association between the degree of tumor PD-L1 expression and outcomes of stage III NSCLC patients treated with durvalumab.
Durvalumab Promising for NSCLC. [2019]The PD-L1 inhibitor durvalumab increases progression-free survival and objective response rate in patients with inoperable and locally advanced stage III non-small cell lung cancer, according to interim results of a phase III trial. The benefit was great enough that the drug could become the standard of care in the United States for these patients.
Durvalumab after definitive chemoradiotherapy in locally advanced NSCLC: Data of the German EAP. [2020]Following the PACIFIC trial, durvalumab has been approved by the European Medicines Agency (EMA) for consolidation of locally advanced PD-L1-positive NSCLC after chemoradiotherapy (CRT). Patients were treated with durvalumab in the EAP from 22.11.2017 to 15.10.2018 allowing analysis of its efficacy and safety. 211 patients were registered by 90 German centres. Data were collected retrospectively by questionnaire and queries. 56 centres reported data on 126 patients who actually received at least one cycle of durvalumab. In contrast to the PACIFIC-trial population, some patients with oligometastatic disease and a history of autoimmune disease are included in the EAP population. Information on PD-L1 status was obtained for 111 patients. Baseline data include age, gender, ECOG, stage (IASLC 8th ed.), and smoking history. Treatment data include mode of chemoradiotherapy, used chemotherapy agent, and duration of durvalumab therapy. Adverse evants were documented according to CTAEC 5.0. Data were analysed for progression-free survival (PFS), overall survival (OS), and adverse events (AE). The results were published in Lung Cancer [1].
Analysis of Tumor Mutational Burden, Progression-Free Survival, and Local-Regional Control in Patents with Locally Advanced Non-Small Cell Lung Cancer Treated With Chemoradiation and Durvalumab. [2023]The addition of consolidative durvalumab to chemoradiation has improved disease control and survival in locally advanced non-small cell lung cancer (NSCLC). However, there remains a need to identify biomarkers for response to this therapy to allow for risk adaptation and personalization.