A Study of Roginolisib (IOA-244) in Combination With Dostarlimab With or Without Docetaxel in Metastatic Non Small-cell Lung Cancer (NSCLC) Patients

NCT06879717 | Active Not Recruiting Phase 1 DMC

• 2 other identifiers: IOA-244-2022024-517741-14
• Study Type: interventional
• Target: 45
• Locations: 3 countries
• Sites: 7

Brief Summary

The goal of this clinical trial is to learn how roginolisib works in combination with dostarlimab with or without docetaxel in adult patients with advanced non small-cell lung cancer. The main questions it aims to answer are: To compare across the treatment arms the proportion of patients with a reduction in Treg cells To evaluate the safety and tolerability of roginolisib plus dostarlimab, with or without docetaxel

Conditions

Non-Squamous Non-Small Cell Lung Cancer (NSCLC); Advanced Non Squamous NSCLC

Keywords

Advanced non-squamous Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (5)

• Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE V5

  Safety measured by AEs

  On Day 1 and Day 15 of Cycle 1; Day 1 of Cycle 2 onwards. Each cycle is 21 days

• To compare across treatment arms the proportion of patients with a reduction in peripheral blood Tregs (for example as defined by CD4+CD25+CD127- expression)

  Change from baseline of at least 50% by Day 42 as assessed by mass cytometry (cytometry by time of flight, CyTOF)

  On Day 1 of each Cycle. Cycle length is 21 days

• Number of Participants With changes in laboratory parameters

  Measures by chemistry and haematology laboratory parameters

  On Day 1and Day 15 of Cycle 1; Day 1 of Cycle 2 onwards. Each cycle is 21 days

• Number of Participants with Changes in ECG from baseline

  Measured by 12 Lead ECG

  On Day 1 and Day 15 of Cycle 1; Day 1 of Cycle 2 onwards. Each cycle is 21 days

• Number of Participants With Change on Physical Examination from Baseline

  Measured by physical examination

  On Day 1and Day 15 of Cycle 1; Day 1 of Cycle 2 onwards. Each cycle is 21 days

Secondary Outcomes (8)

• To further evaluate immune cell subsets in peripheral blood following treatment with roginolisib when given in combination with dostarlimab, and with/without docetaxel

  On Day 1 of each cycle up to 36 weeks. Each cycle is 21 days

• To evaluate preliminary signs of clinical efficacy of roginolisib when given in combination with dostarlimab, and with/without docetaxel

  Every 6 weeks whilst on treatment anticipated to be 36 weeks

• To evaluate preliminary signs of clinical efficacy of roginolisib when given in combination with dostarlimab, and with/without docetaxel

  Every 6 weeks whilst on treatment anticipated to be 36 weeks

• To evaluate preliminary signs of clinical efficacy of roginolisib when given in combination with dostarlimab, and with/without docetaxel

  Every 6 weeks whilst on treatment anticipated to be 36 weeks

• To evaluate preliminary signs of clinical efficacy of roginolisib when given in combination with dostarlimab, and with/without docetaxel

  Every 6 weeks whilst on treatment anticipated to be 36 weeks

Study Arms (3)

Arm 1: Roginolisib + dostarlimab + docetaxel

EXPERIMENTAL

IOA-244 80 mg (corresponding to 72 mg roginolisib) once daily oral dosing on a 21-day cycle. Dostarlimab: 500 mg administered as IV infusion over 30 minutes on Day 1 of every 21-day cycle to a maximum of 35 cycles. Docetaxel: 75 mg/m2 administered over 1 hour as IV infusion on Day 1 of every 21-day cycle.

Drug: roginolisib; Drug: Dostarlimab; Drug: Docetaxel

Arm 2: Roginolisib + dostarlimab

EXPERIMENTAL

IOA-244 80 mg (corresponding to 72 mg roginolisib) once daily oral dosing on a 21-day cycle. Dostarlimab: 500 mg administered as IV infusion over 30 minutes on Day 1 of every 21-day cycle to a maximum of 35 cycles.

Drug: roginolisib; Drug: Dostarlimab

Arm 3: Dostarlimab + docetaxel

ACTIVE COMPARATOR

Dostarlimab: 500 mg administered as IV infusion over 30 minutes on Day 1 of every 21-day cycle to a maximum of 35 cycles. Docetaxel: 75 mg/m2 administered over 1 hour as IV infusion on Day 1 of every 21-day cycle.

Drug: Dostarlimab; Drug: Docetaxel

Interventions

Dostarlimab DRUG

500 mg administered as IV infusion

Arm 1: Roginolisib + dostarlimab + docetaxel; Arm 2: Roginolisib + dostarlimab; Arm 3: Dostarlimab + docetaxel

Docetaxel DRUG

75 mg/m2 administered over 1 hour as IV infusion

Arm 1: Roginolisib + dostarlimab + docetaxel; Arm 3: Dostarlimab + docetaxel

roginolisib DRUG

tablet, 40mg tablet strength

Arm 1: Roginolisib + dostarlimab + docetaxel; Arm 2: Roginolisib + dostarlimab

Eligibility Criteria

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

You may qualify if:

• Male or female ≥18 years of age inclusive, at the time of signing the informed consent.
• Capable of giving signed informed consent, which includes compliance with the requirements of this protocol.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Histologically or cytologically confirmed stage IIIb/IV or recurrent non-squamous NSCLC.
• Have measurable disease per RECIST v1.1 as determined by the investigator. Tumour lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Documented radiographic disease progression on or after prior anti-PD(L)1 therapy and platinum chemotherapy or after standard immunotherapy without chemotherapy in accordance with standard of care.
• Male or female patients of child-bearing potential must be willing to use highly effective forms of contraception (refer to APPENDIX 3 for details on highly effective methods of contraception and definitions of women of childbearing potential \[WOCBP\]and of fertile men):
• Women of childbearing potential (WOCBP) must have a negative serum test as per local guidelines during screening and EOT and agree to have regular urine pregnancy testing throughout the study. WOCBP must agree to use a highly effective method of contraception and refrain from donating eggs throughout the study and until 4 months after last dose of IMP;
• Male patients must agree to use barrier method of contraception \[condom plus spermicide\] from screening through Safety Follow-up visit, at least 1 month after the last dose of IMP. Men should refrain from donating sperm from the day of first dose of IMP, throughout the study and until 3 months after last dose of IMP. Men with partners of child-bearing potential must also be willing to ensure that their partner uses a highly effective method of contraception for the same duration. Men with pregnant or lactating partners should be advised to use barrier method contraception (e.g., condom plus spermicidal gel) to prevent exposure to the foetus or neonate.

You may not qualify if:

• Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications.
• Histologically or cytologically confirmed squamous NSCLC.
• Previously treated with dostarlimab or docetaxel.
• Have prior significant medical history and AEs:
• History of a prior Grade 3 or 4 immune-related AE (irAE) or any grade ocular irAE from prior immunotherapy which did not respond to corticosteroid therapy or resolved with treatment interruptions and returned to at least Grade 1; immunemediated severe neurologic events of any grade (e.g., myasthenic syndrome/myasthenia gravis, encephalitis, Guillain-Barré Syndrome, or transverse myelitis), exfoliative dermatitis of any grade (SJS, TENS, or DRESS syndrome), or myocarditis of any grade.
• Have not recovered from toxic effect(s) of prior therapy to ≤ Grade 1, other than alopecia or fatigue or neuropathy which must be ≤ Grade 2.
• Active autoimmune process (e.g., rheumatoid arthritis, moderate or severe psoriasis, multiple sclerosis, inflammatory bowel disease, immune colitis) that has required systemic treatment in the past 2 years. Replacement therapy (e.g.thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Known active CNS metastases and/or carcinomatous meningitis.
• i. Note: Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks before the first dose of study treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and have not required steroids for at least 7 days before study treatment. e. History of long QT syndrome or history or presence of an abnormal ECG that, in the Investigator's opinion, is clinically meaningful. Screening QTc interval \> 450 milliseconds is excluded (corrected by Fridericia). In the event that a single QTc is \> 450 milliseconds, the patient may enrol if the average QTc for the 3 ECGs is \< 450 milliseconds. For patients with an intraventricular conduction delay (QRS interval \> 120 msec), the JTc interval may be used in place of the QTc with Sponsor approval. The JTc must be \< 340 milliseconds if JTc is used in place of the QTc. Patients with left bundle branch block are excluded.
• f. History of or current risk factor for torsade de pointes (e.g., heart failure, hypokalaemia, or a family history of long QT syndrome). g. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (\< 6 months prior to enrolment), myocardial infarction (\< 6 months prior to enrolment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or any of the following (\<6 months prior to enrolment): acute coronary syndromes, coronary angioplasty or bypass grafting, serious cardiac arrhythmia requiring medication including second degree (Type 2) or third degree AV block, cardiomyopathy, pericarditis or myocarditis.
• h. Any history of interstitial lung disease or pneumonitis. i. History of allogenic stem cell transplantation or organ transplantation. j. Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, oesophageal/ gastric varices, persistent jaundice k. Women who are pregnant or breastfeeding l. Active infection requiring systemic therapy. m. Patients with active malignancy requiring concurrent intervention or previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma or breast) unless a complete remission was achieved at least 2 years prior to study entry and no additional therapy is required during the study period.
• n. Any serious or uncontrolled medical disorder or active infection that, in the opinion of the Investigator, may increase the risk associated with study participation, study drug administration, or would impair the ability of the patient to receive protocol therapy.
• Treatment with anticancer medications, investigational drugs, surgery and/or radiation within the following interval before the first administration of study drug:
• \<90 days for prior taxane.
• \<14 days for chemotherapy, targeted small-molecule therapy, surgical resection of lesions or radiation therapy (prior palliative radiotherapy must have been completed at least 14 days prior to study drug administration). Patients must also not require corticosteroids and must have recovered from pneumonitis as a result of treatment and show no evidence of pneumonitis for at least 1 month. A 1-week washout is permitted for palliative radiation to non-CNS disease with Sponsor approval. Note: The use of denosumab is permitted.

Sponsors & Collaborators

• iOnctura: lead

Study Sites (7)

Antwerp University Hospital

Antwerp, 2650, Belgium

Location

AZ Delta VZW

Roeselare, 8800, Belgium

Location

Istituto Romagnolo per lo studio dei Tumori "Dino Amadori"

Meldola, Forlì-Cesena, 47014, Italy

Location

Humanitas University, Department of Medical Oncology

Rozzano, Milan, 20072, Italy

Location

Institut Català d'Oncologia Hospitalet

Barcelona, 08908, Spain

Location

Hospital Universitari Son Espases

Palma, 07120, Spain

Location

Hospital Universitario y Politécnico La Fe

Valencia, 46026, Spain

Location

MeSH Terms

Interventions

dostarlimab; Docetaxel

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Michael Lahn, MD

  iOnctura

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomised, parallel-arm, comparator controlled, open-label

Study Record Dates

• First Submitted: March 5, 2025
• First Posted: March 17, 2025
• Study Start: April 22, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: January 16, 2026

Record last verified: 2026-01

Locations

BE (2); ES (3); IT (2)