AzTrials
AzTrials

Carcinoma, Non-Small-Cell LungPhase 1NCT03270176

A Dose-Finding Study of the Second Mitochondrial Activator of Caspases (SMAC) Mimetic Debio 1143 When Given in Combination With Avelumab to Participants With Advanced Solid Malignancies and to Participants With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) After Platinum-Based Therapy

A Phase 1 study testing Debio 1143 and Avelumab in people with Carcinoma, Non-Small-Cell Lung and Neoplasms, run by Debiopharm International SA at 9 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The study is primarily designed to assess the safety and tolerability of escalating oral doses of Debio 1143 and preliminary anti-tumour activity when combined with the standard dose of avelumab in participants with advanced solid malignancies. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Carcinoma, Non-Small-Cell Lung, Neoplasms
What is being tested?
Debio 1143 and Avelumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
54 participants
Where
9 sitesin 3 countries
Study dates
10 Oct 2017to 22 Mar 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Part A • With advanced solid malignancies who are not eligible for standard therapy or for whom standard therapy has failed
  • Part B
  • With histologically or cytologically confirmed NSCLC of stage IIIB or IV (per 7th International Association for the Study of Lung Cancer classification) that has progressed after one line of platinum containing doublet chemotherapy
  • Part A and B
  • Willingness and feasibility to provide a tumor biopsy sample both at screening and during treatment (If archived tumor material not older than 1 year is available, then the screening biopsy will not be performed).
  • Participants with prior radiation therapy must have measurable disease in non-irradiated sites or documented evidence of progression within the radiation field.
  • With known central nervous system (CNS) must have completed primary brain therapy (such as whole brain radiotherapy, stereotactic radiosurgery, or complete surgical resection) and must have remained clinically stable, asymptomatic, and without steroid treatment for at least 21 days.

Who cannot join

  • Not recovered (i.e. toxicity grade >1) from prior investigational drug and/or anti-cancer therapy (chemo- or palliative radiotherapy).
  • Symptomatic and/or progressive brain metastasis or carcinomatous meningitis.
  • Immunosuppressive agents (such as steroids) for any reason should be tapered off before initiation of study treatment (except low-dose prednisone at a total dose of up to 10 mg/day).
  • Part B only
  • Tumor activating epidermal growth factor receptor (EGFR) mutation(s) or anaplastic lymphoma kinase (ALK)/ROS1 translocation/rearrangement (testing required in non-squamous participants if status is unknown).
  • More than one prior line of chemotherapy and one line of anti-PD1/PDL1 therapy.

Trial locations and contacts

9 sites in 3 countries.

9 sites in 3 countries

Canada4 sites

  • Cross Cancer Center Dept Medicine

    Edmonton, Alberta, T6G 1Z2

  • Juravinski Cancer Centre

    Hamilton, Ontario, L8V 5C2

  • The Ottawa Hospital Cancer Centre (TOHCC)

    Ottawa, Ontario, K1H 8L6

  • British Columbia Cancer Agency

    Vancouver, British Columbia, V5Z 4E6

Other trials in Canada

Poland3 sites

  • Instytut Medyczny Santa Familia Sp. z o. o.

    Lodz, 90-320

  • Med-Polonia Sp. z o.o., Ulica Obornicka

    Poznan, 60-693

  • Wojewódzki Szpital Zespolony im. Ludwika Rydygiera

    Torun, 87-100

Other trials in Poland

Romania2 sites

  • Institutul Oncologic "Prof. Dr. Ion Chiricuţă" Cluj Napoca

    Cluj-Napoca, 400015

  • Centrul de Oncologie, S.C. Centrul de Oncologie Sf. Nectarie S.R.L, Oncologie Medicala

    Craiova, 200347

Other trials in Romania

About this study

Official title: A Phase-Ib Dose-Finding Study of the SMAC Mimetic Debio 1143 When Given in Combination With the Anti-PD-L1 Antibody Avelumab to Patients With Advanced Solid Malignancies and, in an Expansion Cohort, to Patients With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) After Platinum-Based Therapy

The study is primarily designed to assess the safety and tolerability of escalating oral doses of Debio 1143 and preliminary anti-tumour activity when combined with the standard dose of avelumab in participants with advanced solid malignancies.

Being tested
Debio 1143, Avelumab
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Debio 1143Drug

    Debio 1143 100 to 250 mg, capsule orally for 10 days every 2 weeks.

  • AvelumabDrug

    Avelumab 10 mg/kg intravenous infusion every 2 weeks.

Study groups in NCT03270176
Study groupRoleWhat they receive
Debio 1143 and AvelumabExperimentalPart A: Participants will receive Debio 1143 100 to 250 milligram (mg) capsule orally at an escalating dose levels for 10 days every 2 weeks along with avelumab 10 milligrams per kilogram (mg/kg) as an intravenous (IV) infusion every 2 weeks. Part B: Participants will receive Debio 1143 capsules orally at a recommended phase 2 dose (RP2D) of 200 mg/day (days 1-10 and 15-24 every 28 days ([q4w]) in combination with avelumab IV infusion at the standard dose unless disease progression or unacceptable toxicity occurs, as judged by investigators up to 26 cycles (each cycle is of 28 days).
Receives: Drug: Debio 1143; Drug: Avelumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part A: Maximum Tolerated Dose (MTD)

    MTD:dose with estimated probability of dose limited toxicity(DLT) below 30%.DLT:any of following adverse events(AEs) during 1st treatment cycle if deemed related to treatment:grade (gr) 3/4 febrile neutropenia/any gr 4 neutropenia of >5 days duration;gr 4 thrombocytopenia[<25000 per cubic millimetre(/mm^3)]/gr 3(<50000/mm^3),associated with medically concerning bleeding;gr ≥3 non-hematologic laboratory value;non-hematologic toxicity of gr 3/4,gr ≥2 uveitis/eye pain that does neither respond to topical therapy nor abate to gr 1within the avelumab re-treatment period/that required systemic treatment;gr ≥2 pneumonitis/interstitial lung disease that not resolve with dose delay and systemic steroids;toxicity related to study drug that requires dosing delay of >2weeks,dose reduction,premature discontinuation of any of two;other drug related AE in the opinion of investigator is of potential clinical significance so that further dose-escalation would expose participants to unacceptable risk.

    Measured: Baseline up to Cycle 1 (4 Weeks)

  2. Part B: Objective Response Rate (ORR)

    Objective response is defined as any partial response (PR) or complete response (CR) recorded from the start of study treatment until disease progression/recurrence is documented, a new systemic therapy is started or analysis cut-off, whichever occurs first. It is assessed by using Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1. RECIST v1.1 criteria- CR: disappearance of all target lesions, any pathological lymph nodes must have reduction in short axis to <10 millimeter (mm). PR: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameter.

    Measured: From first occurrence of objective response until disease progression or death from any cause or switch to a new systemic therapy or end of study (Up to 2 years)

Secondary outcomes (9)

  1. Part A and B: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

    An AE is any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. An SAE is any untoward medical occurrence at any dose that results in death; is life-threatening; requires hospitalization; results in persistent or significant disability or in congenital anomaly/birth defect. Severity will be graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.03.

    Measured: Baseline up to 90 days after the last dose of study drug (up to 2.5 years)

  2. Part A and B: Change in Tumor Size

    Change in tumor size is the maximum reduction or, in case of no reduction, the minimum increase in tumor size from the start of study treatment until disease progression/recurrence, the start of a new systemic therapy or analysis cut-off, whichever occurs first.

    Measured: Day 1 of cycle 3 up to 6 months; Day 1 of cycle 9, 12, 15, 18, 21, 24, 26 or until disease progression/EOT (up to 2 years)

  3. Part A and B: Objective Response Rate

    Objective response is defined as any PR or CR recorded from the start of study treatment until disease progression/recurrence is documented, a new systemic therapy is started or analysis cut-off, whichever occurs first. It is assessed by using RECIST criteria. CR: disappearance of all target lesions, any pathological lymph nodes must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameter.

    Measured: At the end of Cycle 6 (168 days)

  4. Part A and B: Best Overall Response (BOR)

    Best overall response (BOR) is defined as the best response (CR, PR, stable disease or disease progression) recorded from the start of study treatment until disease progression/recurrence is documented, a new systemic therapy is started or analysis cut-off, whichever occurs first. It is assessed by using RECIST criteria version 1.1. CR: disappearance of all target lesions, any pathological lymph nodes must have reduction in short axis to <10 millimeter (mm). PR: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameter. Disease progression: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). Stable Disease: Neither sufficient shrinkage to qualify for PR, nor sufficient increase to qualify for disease progression, taking as reference the smallest sum diameter while on study.

    Measured: Day 1 of cycle 3 up to 6 months; Day 1 of cycle 9, 12, 15, 18, 21, 24, 26 or until disease progression/EOT (up to 2 years)

  5. Part A and B: Duration of Response

    Duration of response is the time from documentation of tumor response to disease progression was observed in participants with CR or PR. RECIST v1.1 criteria- CR: disappearance of all target lesions, any pathological lymph nodes must have reduction in short axis to <10 millimeter (mm). PR: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameter. Disease progression: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).

    Measured: Baseline up to Cycle 26 (2 years) or until disease progression/EOT

  6. Part A and B: Disease Control Rate

    Disease control is derived as CR, PR or stable disease lasting at least 16 weeks reported during the study. RECIST v1.1 criteria- CR: Disappearance of all target lesions, any pathological lymph nodes must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameter.

    Measured: Day 1 of cycle 3 up to 6 months; Day 1 of cycle 9, 12, 15, 18, 21, 24, 26 or until disease progression/EOT (up to 2 years)

  7. Part A and B: Progression Free Survival (PFS)

    PFS duration is defined as the time elapsed between treatment initiation and tumor progression or death from any cause, whichever occurs first. RECIST v1.1 criteria- CR: disappearance of all target lesions, any pathological lymph nodes must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameter. Disease progression: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).

    Measured: Up to 6 months, 1 and 2 years of treatment initiation

  8. Part A and B: Overall Survival (OS)

    OS is defined as the time elapsed between treatment initiation and death from any cause.

    Measured: Up to 6 months, 1 and 2 years of treatment initiation

  9. Part A and B: Assessment of Pharmacokinetic Parameters

    Measured: Up to Cycle 25 (700 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Sep 2017
  2. Study start10 Oct 2017
  3. Primary completion22 Mar 2022
  4. Study completion22 Mar 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
54 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03270176
Sponsor's protocol ID
Debio 1143-NSCLC-105
Other IDs
2018-000494-71, 2018
Status last verified
May 2022
First submitted
29 Aug 2017
Last updated
1 Jun 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Goss G, Ciuleanu T, Ramlau R, Renouf DJ, Chu Q, Kalinka E, Sawrycki P, Bramson J, Nelson BH, Crabbe R, LaCasse E, Lo B, Sahlender DA, Crompton P, Brichory F, Piggott L, Schenker M, Juergens R. Xevinapant plus avelumab in advanced solid tumours, with a dose expansion in advanced non-small-cell lung cancer: exploratory biomarker, safety and efficacy analyses from an open-label, nonrandomised phase Ib study. Ther Adv Med Oncol. 2025 May 8;17:17588359251332154. doi: 10.1177/17588359251332154. eCollection 2025.

    PubMed 40351326

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Debio 1143 and Avelumab in people with Carcinoma, Non-Small-Cell Lung and Neoplasms, run by Debiopharm International SA at 9 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Canada, Poland, Romania. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part A: Maximum Tolerated Dose (MTD) (time frame: Baseline up to Cycle 1 (4 Weeks)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03270176, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in
Clinical Trial NCT03270176 | AzTrials