Phase Ib/II trial of the combination of atezolizumab with dendritic cell vaccination as maintenance treatment in patients with extensive stage small cell lung cancer (ES-SCLC) after induction treatment.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Instituto Oncologico Dr. Rosell S.L.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

10 Oct 2024 → 8 Sep 2025

Decision date (initial)

2024-10-10

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-518636-36-00

EudraCT number

2020-000448-72

ClinicalTrials.gov

NCT04487756

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis, Safety, Diagnosis

Progression-free survival (PFS) rate at 6 months.

Secondary objectives 4

1. Duration of clinical benefit (DCB). DCB is calculated as the time (in months) from the first dose of treatment (induction) to PD (or death from any cause) in those patients reported with CR, PR, or SD as the best overall response (ORR) for ≥ 24 weeks.
2. Overall survival (OS).
3. Overall response rate (ORR): Proportion of patients achieving PR or CR during the study induction treatment (ORR1), and proportion of patients with a further response during maintenance treatment (ORR2).
4. Efficacy evaluation (response rate) as per irRECIST.

Conditions and MedDRA coding

Lung Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Histological diagnosis of extensive stage small cell lung cancer (ES-SCLC). Unequivocally confirmed diagnosis of SCLC by histology preferably including the presence of neuroendocrine features by immunohistochemistry.
2. Centrally confirmed tumor tissue viability for ADC immunotherapy preparation.
3. No previous cancer treatment for advanced disease
4. Life expectancy at least 16 weeks
5. ECOG performance status 0 or 1.
6. Adequate normal organ and marrow function as defined below: 6.a Absolute neutrophil count ≥ 1.5 x 10 9 cells/L 6.b Platelets ≥ 100 x 10 9 /L 6.c Hemoglobin ≥ 9 g/dL 6.d Aspartate and alanine aminotransferases (AST, ALT) ≤ 2.5 x upper limit of normal (ULN) (≤ 5 x ULN, if documented liver metastases are present) 6.e Total bilirubin ≤ 2 x ULN (except patients with documented Gilbert's syndrome) 6.f Creatinine < 2 mg/dl (or a glomerular filtration rate > 60)
7. Prior palliative radiotherapy must have been completed at least 2 weeks prior to start the study treatment (subjects may receive localized palliative radiotherapy while receiving study drug).
8. Subjects with brain metastases are eligible if they are asymptomatic, are treated or are neurological stable for at least 2 weeks without the use of steroids or on stable or decreasing dose of < 10 mg daily prednisone or equivalent.
9. Must be willing and able to accept one leukapheresis procedures
10. Written informed consent of approved by the investigator’s Institutional Review Board (IRB)/Independent Ethics Committee (IEC), prior to the performance of any trial activities.
11. Male or female subjects aged ≥ 18 years.
12. Measurable disease by RECIST.1.1 criteria.
13. Highly effective contraception for both male and female subjects throughout the study and for at least 30 days after last atezolizumab treatment administration if the risk of conception exists.
14. Negative serum pregnancy test at screening for women of childbearing potential. Female subjects must either be of non-reproductive potential (ie, post-menopausal by history: ≥60 years old and no menses for ≥1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.
15. Central negative serologic determination to: HBsAg, Anti-HBc, HBV, HCV, HCV RNA, HIV-I RNA, Agp24 IIIV + AC IIIV 1⁄2 (MLIA) serum, IgG antigen core v. hepatitis B, RPR (Ac reagínicos Lues-RPR, serum), Ac anti HTLV I/II (if patient came from endemic zone), Ac anti Trypanosoma Cruzi, Chagas, (if patient came from endemic zone), when RPR positive or doubtful for confirmation: IgG T. pallidum (ELISA) IgM T. pallidum (ELISA), when IgG T. Pallidum doubtful: Pt confirmatory IgG/IGM, T pallidum (LIA). SARS-CoV-2 RNA.

Exclusion criteria 21

1. Prior chemotherapy for extensive-stage ES-SCLC
2. Any prior anti PD-1/PD-L1 antibody therapy
3. History of, or significant evidence of risk for, severe chronic inflammatory or autoimmune disease
4. Potential requirement for systemic corticosteroids or concurrent immunosuppressive drugs based on prior history or received systemic steroids within the last 2 weeks prior to enrollment (inhaled or topical steroids at standard doses are allowed)
5. Human immunodeficiency virus (HIV) seropositivity, active Hepatitis B or C seropositivity (also exclusion of Ags negative with anti Core positive)
6. Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol
7. Pregnancy or breastfeeding; female patients must be surgically sterile or be postmenopausal for two years, or must agree to use effective contraception during the period of treatment and 6 months after; all female patients with reproductive potential must have a negative pregnancy test (serum/urine) within 24 hours from starting the conditioning chemotherapy; the definition of effective contraception will be based on the judgment of the study investigators; patients who are breastfeeding are not allowed on study
8. Any unresolved toxicity (CTCAE grade 2) from previous anti-cancer therapy. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripheral neuropathy).
9. Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, Grave’s disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded. For the phase I cohort, patients with autoimmune paraneoplastic syndromes will be also excluded.
10. Any syndrome that requires systemic corticosteroid/immunosuppressive medication EXCEPT for syndromes which would not be expected to recur in the absence of an external trigger (vitiligo, autoimmune thyroiditis, or type 1 diabetes mellitus are permitted to enroll)
11. Active or prior documented inflammatory bowel disease (e.g., Crohn’s disease, ulcerative colitis).
12. History of primary immunodeficiency.
13. History of allogeneic organ transplant.
14. History of hypersensitivity to atezolizumab / ADC immunotherapy or any excipient.
15. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diathesis including any subject known to have evidence of acute or chronic hepatitis B or C, or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent.
16. Known history of active tuberculosis.
17. Subjects with previous malignancies (except for non melanoma skin cancer, and cancer in situ of: bladder, gastric, colon, cervical/dysplasia, melanoma, breast) are excluded unless a complete remission was achieved at least 5 years prior to study entry and no additional therapy is required or anticipated to be required during the study period.
18. Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving atezolizumab. Note: For COVID vaccination, every case should be first consulted with the Clinical Trial Coordinator. Decisions to administer vaccine should be individualized by the physicians and in consultation with the patients and based on the risk of SARS-CoV-2 infection/complications and potential benefit from the vaccine, the general condition of the patient, underlying disease, and the severity of COVID-19 outbreak in a given area/ region.
19. Prior allogeneic stem-cell transplantation.
20. Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥ 3 NCI-CTCAE v 5.0), any history of anaphylaxis, or uncontrolled asthma.
21. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ highly effective birth control from screening to 180 days after the last dose of ADC + atezolizumab combination therapy.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-Free Survival (PFS) rate at 6 months: Calculated as the percentage of participants alive and without disease progression, as assessed by the Investigator using RECIST v1.1, at 6 months.

Secondary endpoints 3

1. Duration of clinical benefit (DCB) as per RECIST 1.1: DCB calculated as the time (in months) from first dose of treatment to progression (or death from any cause) in patients who had a best overall response of CR, PR, or SD of ≥ 24 weeks.
2. Overall Survival (OS): Overall Survival (OS) is calculated as the time from date of inclusion to date of death due to any cause.
3. Response rate (ORR): rate of patients that achieve partial or complete response as best response during study induction treatment (ORR1) and rate of patients that have a further best response during maintenance treatment (ORR2).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Instituto Oncologico Dr. Rosell S.L.

Sponsor organisation

Instituto Oncologico Dr. Rosell S.L.

Address

Calle De Sabino Arana Num. 5

City

Barcelona

Postcode

08028

Country

Spain

Scientific contact point

Organisation

Instituto Oncologico Dr. Rosell S.L.

Contact name

A person designed by the Sponsor

Public contact point

Organisation

Instituto Oncologico Dr. Rosell S.L.

Contact name

A person designed by the Sponsor

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications