Continued PD-L1 inhibition with atezolizumab with rechallenge chemotherapy in patients with sensitive relapse SCLC progressing on first-line platinum-etoposide chemotherapy and a PD-L1 inhibitor: CARRY-ON study - GOIRC-01-2023

Overview

Sponsor-declared trial summary

Key facts

Sponsor

G.O.I.R.C. Gruppo Oncologico Italiano Di Ricerca Clinica

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

24 Jan 2025 → ongoing

Decision date (initial)

2024-09-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

ROCHE S.P.A.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

The primary objective of the study is to explore the efficacy of a second-line experimental regimen in which atezolizumab is added to standard PE chemotherapy, in patients with sensitive ES-SCLC progressing after first-line chemo-immunotherapy in term of overall survival.

Secondary objectives 2

1. to evaluate the safety of a second-line experimental regimen in which atezolizumab is added to standard PE chemotherapy, in patients with sensitive ES-SCLC progressing after first-line chemo-immunotherapy
2. to evaluate the activity of a second-line experimental regimen in which atezolizumab is added to standard PE chemotherapy, in patients with sensitive ES-SCLC progressing after first-line chemo-immunotherapy in terms of objective response and progression-free survival.

Conditions and MedDRA coding

patients affected by small cell lung cancer (SCLC)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Diagnosis of small-cell lung cancer (SCLC) (according to WHO classification 2015) confirmed at pathology (histology or cytology).
2. Male or female and ≥ 18 years of age
3. Life expectancy ≥ 12 weeks
4. Disease progression at least 60 days after the completion of first-line chemotherapy consisting of at least 4 cycles of platinum-etoposide plus either atezolizumab or durvalumab and have not received any other treatment (except for immunotherapy as maintenance treatment); the 60 day-interval is calculated from the date of the last chemotherapy administration to the date of the first radiologically documented progressive disease
5. No previous radiotherapy on the only one site of disease progression, unless that lesion had subsequent evidence of progressive disease
6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2
7. Patients with treated brain metastases (or untreated but asymptomatic) and off steroids or on a stable dose of steroids (≤10 mg of prednisone-equivalent) are also eligible. Radiotherapy must have been completed a minimum of 14 days prior to registration, and patients must have recovered from AEs related to radiotherapy to < grade 1 (except alopecia)
8. For Females: must be postmenopausal (defined as occurring 12 months after last menstrual period) before the screening visit, or are surgically sterile. If they are of childbearing potential, a negative serum pregnancy test prior to study entry has to be documented; furthermore, they agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form (ICF) through 5 months after the last dose of study drug, or agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject
9. For Males: even if surgically sterilized (i.e. post-vasectomy status) agree to practice effective barrier contraception during the entire study treatment period and through 6 months after the last dose of study drug, or practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject
10. Normal baseline laboratory values
11. Stable medical condition, including the absence of acute exacerbations of chronic illnesses, serious infections, or major surgery within 4 weeks before registration, and otherwise noted in other inclusion/exclusion criteria
12. Recovered (i.e., ≤ Grade 1 toxicity) from effects of prior anticancer therapy, except alopecia
13. Prior radiotherapy is allowed provided that it has been completed more than 2 weeks before starting protocol treatment and patients have recovered from AEs related to radiotherapy to < grade 1
14. Ability to comply with protocol requirements
15. The patient or the patient’s legal representative has to be able to provide written informed consent. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care

Exclusion criteria 21

1. More than 1 line of prior treatment for SCLC
2. Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 drug elimination half-lives (whichever is longer) prior to initiation of study treatment except for PD-L1 inhibitor maintenance as part of first-line treatment.
3. Any condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of randomization. The following are exceptions to this criterion: o Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection); o Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent; o Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
4. Diagnosed with or treated for another malignancy within 3 years before the first dose of study drug, or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type may be enrolled in the study if they have undergone complete resection and no evidence of active disease is present.
5. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment other than those in the present study. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
6. Treatment with any other investigational agent within 30 days prior to starting study treatment, 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.
7. Infection requiring intravenous antibiotic therapy or other serious infection within 14 days before the first dose of study drug.
8. Prior allogeneic stem cell or solid organ transplantation.
9. For female subjects: positive serum pregnancy test, pregnancy, or breastfeeding.
10. Surgery within 4 weeks (or 2 weeks for a minor surgery) before study enrolment and not fully recovered to baseline or to a stable clinical status. Insertion of a vascular device is allowed.
11. Patients who experienced medically significant or NCI CTCAE Grade ≥3 or higher toxicities in response to first-line immunotherapy
12. First-line treatment without either atezolizumab or durvalumab
13. Unwilling or unable to comply with the protocol or cooperate fully with the investigator and site personnel.
14. First-line chemotherapy different from platinum-etoposide
15. Less than 4 cycles of first-line platinum-etoposide
16. Presence of resistant relapse (progressive disease within 60 days from the end of first-line chemotherapy) or refractory disease (progressive disease during the first 4 cycles of first-line chemoimmunotherapy).
17. Symptomatic brain metastases or spinal cord compression (CT or MRI of the head is required within 4 weeks prior to randomization) requiring immediate radiotherapy for palliation. Patients with treated brain metastases (or untreated but asymptomatic) and off steroids or on a stable dose of steroids (≤10 mg of prednisone-equivalent) are also eligible provided that all of the following criteria are met:
18. If treated, at least 14 days between the end of stereotactic radiotherapy or whole brain radiotherapy and initiation of study treatment and recovery from Aes related to radiotherapy to ≤ grade 1 (except alopecia), or at least 28 days between neurosurgical resection and initiation of study treatment; o Anticonvulsant therapy at a stable dose is permitted; o Metastases are limited to the cerebellum or the supratentorial region (i.e., no metastases to the midbrain, pons, medulla or spinal cord); o There is no evidence of interim progression between completion of CNS directed therapy (if administered) and initiation of study treatment.
19. Evidence of leptomeningeal disease.
20. Patient has received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.
21. Any comorbid condition or unresolved toxicity that would preclude administration of second-line chemotherapy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. overall survival (OS), defined as the time from the date of enrollment registration to the date of death from any cause. Patients still alive at the time of analysis are censored at the last time they are known to be alive.

Secondary endpoints 3

1. Toxicity: the assessment of safety will be based mainly on the frequency of adverse events; toxicity will be measured according to NCI Common Toxicity Criteria Adverse Event (CTCAE), version 5.0.
2. Progression Free Survival (PFS) defined as the time from the patient enrollment registration to the evidence of progressive disease, or death, or the last date the patient was known to be progression-free or alive.
3. Objective response rate (ORR): the sum of RECIST v1.1-defined CR and PR out of the number of assessable patients with measurable disease at baseline.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

G.O.I.R.C. Gruppo Oncologico Italiano Di Ricerca Clinica

Sponsor organisation

G.O.I.R.C. Gruppo Oncologico Italiano Di Ricerca Clinica

Address

Viale Antonio Gramsci 14

City

Parma

Postcode

43126

Country

Italy

Scientific contact point

Organisation

G.O.I.R.C. Gruppo Oncologico Italiano Di Ricerca Clinica

Contact name

Prof. Ardizzoni Andrea

Public contact point

Organisation

G.O.I.R.C. Gruppo Oncologico Italiano Di Ricerca Clinica

Contact name

Prof. Ardizzoni Andrea

Locations

1 EU/EEA country · 25 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 9 files

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

Application history

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