AZD2811 and Durvalumab (MEDI4736) Combination Therapy in Relapsed Small Cell Lung Cancer

NCT04525391 | Terminated Phase 2

• 1 other identifier: SUKSES-N5
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

Samsung Medical Centre, Seoul, Korea. Additional 0\~5 Korea Lung Cancer Consortium (KLCC) centres in Korea Up to 40 subjects will be enrolled in two-stages (first stage: 19 evaluable subjects and second stage: 17 evaluable subjects and additional 4 subjects considering the drop out rate) If the study is conducted as de-escalated dosage (Durvalumab 1120mg) after the safety run-in, number of the patients will be counted from the second safety-run in phase.

Conditions

SCLC, Recurrent

Outcome Measures

Primary Outcomes (1)

• Disease control rate is defined as the proportion of patients with best response of CR, PR, or who have SD for at least 12 weeks

  To investigate the efficacy of AZD2811 and durvalumab combination therapy in subjects with relapsed SCLC subjects with c-MYC expression ≥ 1+ as 2nd or 3rd line therapy

  12 weeks

Secondary Outcomes (4)

• Duration of response (SD, PR, CR) calculated by Kaplan-Meier method

  12 weeks

• Overall survival(OS) calculated by Kaplan-Meier method

  12 weeks

• Progression-free survival(PFS) calculated by Kaplan-Meier method

  12 weeks

• Time to first relapse (resistant relapse or sensitive relapse)

  12 weeks

Study Arms (1)

Durvalumab+AZD2811 to SCLC patients

EXPERIMENTAL

Dosage and Schedule: AZD2811 500mg and durvalumab 1500mg via IV administered on Day 1 for every 3weeks (fixed dosing for subjects \> 30 kg body weight for durvalumab). One cycle is consisted of 3 weeks. The drug products must be dosed consecutively using different infusion lines. The sequence of infusions is as follows: durvalumab is administered first over 1 hour, followed by AZD2811 administered over 2 hours. A waiting time interval of at least 30 minutes between the end of durvalumab infusion and start of AZD2811 infusion should be adhered to.

Drug: Durvalumab+AZD2811 to SCLC patients

Interventions

Durvalumab+AZD2811 to SCLC patients DRUG

AZD2811 must NOT be infused through a 0.2-µm or 0.22-µm filter and therefore durvalumab and AZD2811 MUST be infused through different infusion lines. In order not to exceed the endotoxin limit, durvalumab and AZD2811 mustbe administered consecutively. Durvalumab is administered first over 1 hour, followed by AZD2811 administered over 2 hours. AZD2811 should be administered at 30 minutes after the end of the durvalumab infusion, as long as there are no acute infusion reactions to durvalumab.

Durvalumab+AZD2811 to SCLC patients

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of fully informed consent prior to any study specific procedures.
• Subjects must be ≥ 18 years of age.
• Body weight \> 30kg
• Small cell lung cancer that has progressed during or after first-line therapy.
• The 1st line regimen must have contained platinum based regimen and must have documented radiological and/or clinical progression on treatment.
• Refractory to first-line chemotherapy or relapse within 6 months since the last dose of first-line chemotherapy
• If the subject has sensitive relapse (relapse more than 6 months since the last dose of first-line chemotherapy), (s)he should receive second-line treatment prior to study entry.
• Histologically confirmed SCLC with documented c-MYC expression (≥ c-MYC IHC 1+)
• Subjects are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
• ECOG performance status 0-1
• Subjects must have a life expectancy ≥ 3months from proposed first dose date.
• Subjects must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
• Haemoglobin ≥ 9.0g/dL)
• White blood cells (WBC) ≥ 3 x 109/L
• Platelet count ≥ 100 x 109/L

You may not qualify if:

• Previous enrolment in the present study or 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
• More than two prior chemotherapy regimens for the treatment of small cell lung cancer refractory to first-line chemotherapy or relapse within 6 months.
• (However, immunotherapy is not counted the prior chemotherapy regimen.)
• Subjects with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for \> 2 years. Or patients with a history of leptomeningeal carcinomatosis.
• Treatment with any investigational product during the last 14 days before the first dose on study.
• Subjects receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks from the last dose prior to study treatment (or a longer period depending on the defined characteristics of the agents used). The subject can receive a stable dose of bisphosphonates or denosumab for bone metastases, before and during the study as long as these were started at least 4 weeks prior to treatment.
• Receiving, or having received, concomitant medications, herbal supplements and/or foods that significantly modulate cytochrome P450 3A4(CYP3A4) or P-glycoprotein(P-gp) activity (washout periods of 2 weeks, but 3 weeks for St. John's Wort). Note these include common azole antifungals, macrolide antibiotics and other medications.
• Prior exposure to an AURKB inhibitor or PD-1 or PD-L1 or CTLA-4 inhibitor.
• Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:
• Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection)
• Systemic corticosteroids at physiologic doses not to exceed 10mg/day of prednisone or its equivalent
• Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication)
• Receipt of live attenuated vaccine within 30 days prior to the first dose of investigational product. Note: Subjects, if enrolled, should not receive live vaccine whilst receiving investigational product and up to 180 days after the last dose of investigational product.
• Subjects with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Investigator.
• Subjects with irreversible toxicity not reasonably expected to be exacerabated by treatment with durvalumab may be included only after consultation with with the Investigator.

Sponsors & Collaborators

• Se-Hoon Lee: lead

Study Sites (1)

Samsung Medical Center

Seoul, Gangnam-gu, South Korea

Location

MeSH Terms

Conditions

Recurrence

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 14, 2020
• First Posted: August 25, 2020
• Study Start: September 18, 2020
• Primary Completion: January 14, 2022
• Study Completion: January 14, 2022
• Last Updated: February 25, 2022

Record last verified: 2022-02

Locations

KR (1)