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

Inclusion Criteria:

1. Male or female ≥18 years of age inclusive, at the time of signing the informedconsent.

2. Capable of giving signed informed consent, which includes compliance with therequirements of this protocol.

3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

4. Histologically or cytologically confirmed stage IIIb/IV or recurrent non-squamousNSCLC.

5. Have measurable disease per RECIST v1.1 as determined by the investigator. Tumourlesions situated in a previously irradiated area are considered measurable ifprogression has been demonstrated in such lesions.

6. Documented radiographic disease progression on or after prior anti-PD(L)1 therapyand platinum chemotherapy or after standard immunotherapy without chemotherapy inaccordance with standard of care.

7. Male or female patients of child-bearing potential must be willing to use highlyeffective forms of contraception (refer to APPENDIX 3 for details on highlyeffective methods of contraception and definitions of women of childbearingpotential [WOCBP]and of fertile men):

8. Women of childbearing potential (WOCBP) must have a negative serum test as perlocal guidelines during screening and EOT and agree to have regular urinepregnancy testing throughout the study. WOCBP must agree to use a highlyeffective method of contraception and refrain from donating eggs throughout thestudy and until 4 months after last dose of IMP;

9. Male patients must agree to use barrier method of contraception [condom plusspermicide] from screening through Safety Follow-up visit, at least 1 monthafter the last dose of IMP. Men should refrain from donating sperm from the dayof first dose of IMP, throughout the study and until 3 months after last doseof IMP. Men with partners of child-bearing potential must also be willing toensure that their partner uses a highly effective method of contraception forthe same duration. Men with pregnant or lactating partners should be advised touse barrier method contraception (e.g., condom plus spermicidal gel) to preventexposure to the foetus or neonate.

Exclusion Criteria:

1. Inability to swallow food or any condition of the upper gastrointestinal tract thatprecludes administration of oral medications.

2. Histologically or cytologically confirmed squamous NSCLC.

3. Previously treated with dostarlimab or docetaxel.

4. Have prior significant medical history and AEs:

5. History of a prior Grade 3 or 4 immune-related AE (irAE) or any grade ocularirAE from prior immunotherapy which did not respond to corticosteroid therapyor resolved with treatment interruptions and returned to at least Grade 1;immunemediated severe neurologic events of any grade (e.g., myasthenicsyndrome/myasthenia gravis, encephalitis, Guillain-Barré Syndrome, ortransverse myelitis), exfoliative dermatitis of any grade (SJS, TENS, or DRESSsyndrome), or myocarditis of any grade.

6. Have not recovered from toxic effect(s) of prior therapy to ≤ Grade 1, otherthan alopecia or fatigue or neuropathy which must be ≤ Grade 2.

7. Active autoimmune process (e.g., rheumatoid arthritis, moderate or severepsoriasis, multiple sclerosis, inflammatory bowel disease, immune colitis) thathas required systemic treatment in the past 2 years. Replacement therapy (e.g.thyroxine, insulin, or physiologic corticosteroid replacement therapy foradrenal or pituitary insufficiency, etc.) is not considered a form of systemictreatment.

8. Known active CNS metastases and/or carcinomatous meningitis. i. Note: Patients with previously treated brain metastases may participate providedthey are stable (without evidence of progression by imaging for at least 4 weeksbefore the first dose of study treatment and any neurologic symptoms have returnedto baseline), have no evidence of new or enlarging brain metastases, and have notrequired steroids for at least 7 days before study treatment. e. History of long QTsyndrome or history or presence of an abnormal ECG that, in the Investigator'sopinion, is clinically meaningful. Screening QTc interval > 450 milliseconds isexcluded (corrected by Fridericia). In the event that a single QTc is > 450milliseconds, the patient may enrol if the average QTc for the 3 ECGs is < 450milliseconds. 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 withleft 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 monthsprior to enrolment), myocardial infarction (< 6 months prior to enrolment), unstableangina, congestive heart failure (≥ New York Heart Association Classification ClassII), or any of the following (<6 months prior to enrolment): acute coronarysyndromes, coronary angioplasty or bypass grafting, serious cardiac arrhythmiarequiring 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 allogenicstem cell transplantation or organ transplantation. j. Cirrhosis or current unstableliver or biliary disease per investigator assessment defined by the presence ofascites, encephalopathy, coagulopathy, hypoalbuminemia, oesophageal/ gastricvarices, persistent jaundice k. Women who are pregnant or breastfeeding l. Activeinfection requiring systemic therapy. m. Patients with active malignancy requiringconcurrent 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 atleast 2 years prior to study entry and no additional therapy is required during thestudy period. n. Any serious or uncontrolled medical disorder or active infection that, in theopinion of the Investigator, may increase the risk associated with studyparticipation, study drug administration, or would impair the ability of the patientto receive protocol therapy.

9. Treatment with anticancer medications, investigational drugs, surgery and/orradiation within the following interval before the first administration of studydrug:

10. <90 days for prior taxane.

11. <14 days for chemotherapy, targeted small-molecule therapy, surgical resectionof lesions or radiation therapy (prior palliative radiotherapy must have beencompleted at least 14 days prior to study drug administration). Patients mustalso not require corticosteroids and must have recovered from pneumonitis as aresult 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 withSponsor approval. Note: The use of denosumab is permitted.

12. < 14 days for a prior PD1 pathway-targeted agent.

13. < 28 days for prior monoclonal antibody used for anticancer therapy with theexception of PD1 pathway-targeted agents.

14. < 28 days or 5 half-lives (whichever is longer) before the first dose for allother investigational study drugs or devices. For investigational agents withlong halflives (e.g., > 5 days), enrolment before the fifth half-life requiresMedical Monitor approval.

15. Radiotherapy -At least 6 weeks from prior radioisotope therapy. Note:Investigational agents that are not designed as antineoplastic treatment butused in combination with standard therapies are allowed.

16. Receiving an immune-suppressive based treatment for any reason (including chronicuse of systemic corticosteroid at doses > 10 mg/day prednisone equivalent) within 14days prior to the first dose of study treatment. Use of inhaled or topical steroids (including but not limited to creams or intra-articular injection) or briefcorticosteroid use for radiographic procedures or systemic corticosteroids ≤ 10 mgis permitted.

17. Have received a live vaccine within 30 days of planned start of study therapy whileon trial. With regards to other type of vaccines, including SARS-Co2 vaccines, areallowed.

18. Known allergy or reaction to any component of either study drugs or formulationcomponents.

19. Known alcohol or other substance abuse.

20. Laboratory and medical history parameters not within Protocol-defined range. Cycle 1Day 1 laboratory assessments for the determination of eligibility do not need to beperformed if the screening laboratory assessments were performed within 7 days ofCycle 1 Day 1. If the screening laboratory assessments were performed more than 7days before Cycle 1 Day 1, then the haematology and serum chemistry laboratoryresults must be confirmed up to 3 days before treatment initiation on Cycle 1 Day 1.

21. Absolute neutrophil count < 1.5 × 109/L.

22. Platelet count < 100 × 109/L.

23. Haemoglobin < 9 g/dL (transfusion is acceptable to meet this criterion).

24. Serum creatinine ≥ 1.5 × institutional upper limit of normal (ULN) or measuredor calculated creatinine clearance (CrCl) (glomerular filtration rate can alsobe used in place of creatinine or CrCl) < 50 mL/min for patients withcreatinine levels > 1.5 × institutional ULN.

25. Aspartate aminotransferase (AST) or ALT ≥ 2.5 × ULN in the absence of hepaticmetastases or ≥ 5 × ULN with hepatic metastases at screening.

26. Total bilirubin ≥ 1.2 × ULN are excluded unless direct bilirubin is ≤ ULN. Ifthere is no institutional ULN, then direct bilirubin must be < 40% of totalbilirubin to be eligible (except patients with Gilbert syndrome, who must havetotal bilirubin < 51.3 μmol/L).

27. International normalized ratio or prothrombin time (PT) > 1.5 × ULN.

28. Activated partial thromboplastin time (aPTT) > 1.5 × ULN.

29. Evidence of acute infection of hepatitis B virus (HBV), (for example: positivefor HBsAg, anti-HBc, IgM anti-HBc and negative for anti-HBs), hepatitis C virus (HCV) (for example: HCV antibody reactive; HCV RNA detected) and HumanImmunodeficiency Virus (HIV). Patients who are on stable antiviral therapy fortheir viral infection of hepatitis (e.g., HBV, HCV) or HIV (i.e., for at least 12 months) and willing to remain on these during and for 6 months after end ofstudy treatment, and/or asymptomatic are eligible for the study.