Cemiplimab for Non-small cell lung cancer

Inclusion criteria

• {"criterion_text":"- At least 18 years of age at the time of signing the Informed Consent Form (ICF) prior to initiation of any study specific activities/procedures.\n- Women of childbearing potential (WOCBP) must have negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 72 hours prior to receiving the first administration of IP.\n- Contraception use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Refer to Appendix 4, Section 10.4 for details and definitions of WOCBP, postmenopausal females and contraception guidance.\n- WOCBP must agree to use a highly effective birth control and refrain from oocyte donation during the study (prior to the first dose with THIO, for the duration of the treatment with THIO plus 6 months after last dose of IP), if conception is possible during this interval.\n- Male subjects and WOCBP partners of male subjects should use a combination of the methods specified in Section 10.4 for the women along with a male condom from first dose of THIO (Cycle 1, Day 1), for the duration of the treatment with THIO plus 6 months after last dose of IP, unless permanently sterile by bilateral orchidectomy. Male subjects should also refrain from sperm donation during this time.\n- Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.\n- Stage 3 or 4 histologically or cytologically confirmed NSCLC which has progressed or relapsed after treatment in the advanced setting ○\tStage 4 subjects: \tPart A and Part B: must have progressed or relapsed after first line treatment. \tPart C and Part D: must have progressed, discontinued due to toxicity, or relapsed after receiving (only) two prior lines of treatment for NSCLC in the advanced setting. ○\tStage 3 subjects – must have already failed, or be ineligible for, local, curative-intent therapy including surgery, and/or chemoradiation. Stage 3 subjects with documented relapse/progression after consolidation therapy with durvalumab following definitive chemoradiotherapy are eligible.\n- Subjects must have secondary resistance to the prior ICI, as defined by the Society for Immunotherapy of Cancer (SITC) Immunotherapy Resistance Task Force (IRTF) (Kluger 2020) Note: Subjects with drug exposure > 6 weeks who achieved a PR or CR then progressed before 6 months, would still be eligible.\n- Part A and Part B: Only one prior treatment for NSCLC in the advanced setting, which must have included one anti-PD-1/PD-L1 agent with documented radiographic disease progression on or after treatment. ○\tPrior treatment may have been with anti-PD-1/PD-L1 agent either alone or in combination with a non-anti-PD-1/PD-L1 treatment (e.g., chemotherapy) ○\tPrior platinum-based chemotherapy is not required for eligibility. ○\tSubjects receiving more than one ICI in the advanced setting (e.g., anti-PD-1/PD-L1 and anti-CTLA-4 compounds) will not be eligible. Part C and Part D: Only two prior treatments for NSCLC in the advanced setting, which must have included an anti-PD-1/PD-L1 agent, a platinum-based chemotherapy, and docetaxel, regardless of order or combination, with documented radiographic disease progression, intolerable toxicity, or relapse after treatment. ○\tCombination of immune therapy is allowed (e.g., anti-PD-1/PD-L1 and anti-CTLA-4 compounds; anti-PD-1/PD-L1 and T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain (TIGIT)-based immunotherapy).\n- No prior targeted therapy for driver mutations.\n- At least one measurable target lesion that meets the definition of RECIST v1.1.\n- Part A and Part B: An archival tissue sample (formalin fixed paraffin-embedded [FFPE] tissue block or unstained slides) is required if tissue is available at baseline. Sample does not need to be received by central lab prior to Cycle 1, Day 1 (C1D1). Subjects without archival tissue available at baseline may be eligible with Medical Monitor approval. Part C and Part D: Blood sample collection at baseline is not required. Archival tissue is optional for Parts C and D. Sites will only collect archival tissue at the sponsor’s request.\n- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.\n- Demonstrate adequate organ function as defined below. All screening laboratories should be performed up to 14 days before initiating IP: Bone marrow function: ○\tNeutrophil count ≥ 1500/mm3, hemoglobin ≥ 9.0 g/dL, platelet count ≥ 100,000/mm3 Liver function: ○\tTotal bilirubin ≤ 1.5 x the upper limit of normal (ULN), up to ≤ 3 × ULN due to Gilbert’s syndrome ○\tAlanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 × ULN. For subjects with liver metastases present at baseline, ALT and/or AST ≤ 3 × ULN is permitted. Renal function: ○\tCreatinine clearance ≥ 60 mL/min calculated by the Cockcroft-Gault formula using actual body weight (see Table 15) or 24-hour urine collection. For Asian countries, a creatinine clearance of ≥ 50 mL/min calculated by the Cockcroft-Gault formula using actual body weight (see Table 15) or 24-hour urine collection is acceptable."}

Exclusion criteria

• {"criterion_text":"- Have not recovered from adverse events (must be Grade ≤ 1) due to prior anti-cancer treatment.\n- Active autoimmune diseases or history of autoimmune diseases that may relapse, with the following exceptions: ○\tControlled type 1 diabetes; ○\tHypothyroidism (provided it is managed with hormone replacement therapy only); ○\tControlled celiac disease; ○\tSkin diseases not requiring systemic treatment (e.g., vitiligo, psoriasis, or alopecia); ○\tAny other disease that is not expected to recur in the absence of external triggering factors.\n- Pregnancy or lactating.\n- A serious nonmalignant disease (e.g., psychiatric, substance abuse, uncontrolled intercurrent illness, etc.) that could compromise protocol objectives in the opinion of the investigator and/or the Sponsor.\n- Any other condition that, in the opinion of the investigator, would prohibit the subject from participating in the study.\n- Part C and Part D: more than two prior systemic treatments for advanced disease.\n- Prior chemotherapy and/or non-biologic targeted therapy within 4 weeks, or biologic targeted therapy, immunotherapy, and/or radiation therapy within 6 weeks prior to Cycle 1 Day 1. Subjects who receive targeted radiation therapy for localized palliative care may be eligible to start treatment < 6 weeks with Medical Monitor agreement.\n- Part A and Part B: Prior treatment with cemiplimab. Note: Part C and Part D: prior cemiplimab is permitted.\n- For subjects who have received prior treatment with an ICI: primary resistance to prior ICI therapy, as defined by the SITC IRTF (Kluger 2020) Note: Subjects with drug exposure > 6 weeks who achieved a partial or complete response then progressed before six months, would still be eligible.\n- Undergone major surgery within 4 weeks prior to Cycle 1, Day 1.\n- Received blood, red blood cell or platelet transfusion within 2 weeks before the first dose of IP.\n- Untreated or symptomatic central nervous system (CNS) metastases. Note: subjects with treated asymptomatic brain metastasis are eligible.\n- Any live, attenuated, inactivated or research vaccines within 30 days prior to the first dose of IP. Refer to Section 6.9.1 for prohibited vaccines. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed.\n- Prior allogeneic hematopoietic stem cell transplant or solid organ transplant.\n- Currently enrolled in a clinical study involving another IP or nonapproved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.\n- History of allergy to excipients of THIO or cemiplimab.\n- Active gastrointestinal bleeding as evidenced by either hematemesis or melena.\n- History of another concurrent malignancy other than the present condition (except nonmelanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission and off all therapy for that disease for a minimum of 3 years.\n- A condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, adrenal replacement doses 10 mg daily prednisone equivalents, and systemic corticosteroids to manage adverse events (AEs) are permitted in the absence of active autoimmune disease.\n- Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy within 2 weeks of screening.\n- Positive for Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies), active hepatitis B or hepatitis C.\n- Significant cardiovascular impairment (history of New York Heart Association Functional Classification System Class III or IV) or a history of myocardial infarction or unstable angina within the past 6 months prior to IP initiation. a)\tQTcF > 480 msec at screening (based on average of triplicate ECGs at baseline). i.\tIf the QTc is prolonged in a subject with a pacemaker or bundle branch block, the subject may be enrolled in the study if confirmed by the Medical Monitor.\n- Ongoing immune-related/stimulated adverse events (irAEs) from other agents or required permanent discontinuation of prior ICIs due to irAEs. Subjects with resolved irAE may be allowed to enroll following consultation with Sponsor’s Medical Monitor (or designee)."}

Primary endpoints

• {"endpoint_text":"- Part A: Incidence of DLTs.","definition_or_measurement_approach":""}
• {"endpoint_text":"- Part C: ORR, defined as the proportion of subjects with either a CR or PR, as assessed by the investigator based on RECIST v1.1 (Safety endpoints: see below)","definition_or_measurement_approach":"ORR measured as proportion with CR or PR per investigator assessment using RECIST v1.1."}
• {"endpoint_text":"- Part D: ORR, defined as the proportion of subjects with a confirmed CR or PR, as assessed by BICR based on RECIST v1.1","definition_or_measurement_approach":"ORR measured as proportion with confirmed CR or PR assessed by blinded independent central review (BICR) using RECIST v1.1."}
• {"endpoint_text":"- Part A and Part B: Incidence of TEAEs, and SAEs overall, by severity, by relationship to THIO and/or cemiplimab, and those that led to discontinuation of THIO and cemiplimab and/or withdrawal from study","definition_or_measurement_approach":"Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) summarized overall, by severity and relationship to study drugs; events leading to discontinuation or withdrawal captured."}
• {"endpoint_text":"- Part A and Part B: •\tORR, defined as the proportion of subjects with either a CR or PR, as assessed by the investigator based on RECIST v1.1 •\tDCR defined as the proportion of subjects with CR, PR, or SD, as assessed by the investigator based on RECIST v1.1","definition_or_measurement_approach":"ORR and DCR assessed by investigator using RECIST v1.1; ORR = CR or PR proportion; DCR = CR, PR or SD proportion."}

Secondary endpoints

• {"endpoint_text":"- Part A and Part B: DoR, PFS, and OS","definition_or_measurement_approach":"Duration of Response (DoR), Progression-Free Survival (PFS), and Overall Survival (OS); assessment methods not detailed in CTIS summary."}
• {"endpoint_text":"- Part C: •\tDoR, DCR, PFS, as assessed by the Investigator based on RECIST v1.1 •OS","definition_or_measurement_approach":"DoR, DCR, PFS assessed by Investigator using RECIST v1.1; OS measured as time to death."}
• {"endpoint_text":"- Part D: •\tDoR, DCR, PFS, as assessed by BICR based on RECIST v1.1 •ORR, DoR, DCR, PFS, as assessed by the Investigator based on RECIST v1.1 OS","definition_or_measurement_approach":"DoR, DCR, PFS assessed by BICR (RECIST v1.1); ORR/DoR/DCR/PFS also assessed by Investigator per RECIST v1.1; OS measured as time to death."}

Bulgaria

Earliest CTIS Part Ii Submission Date

12-06-2024

Latest Decision Or Authorization Date

21-01-2025

Processing Time Days

223

Number Of Sites

5

Number Of Participants

23

Hungary

Earliest CTIS Part Ii Submission Date

12-06-2024

Latest Decision Or Authorization Date

13-04-2026

Processing Time Days

670

Number Of Sites

7

Number Of Participants

70

Poland

Earliest CTIS Part Ii Submission Date

12-06-2024

Latest Decision Or Authorization Date

13-04-2026

Processing Time Days

670

Number Of Sites

15

Number Of Participants

100

Romania

Earliest CTIS Part Ii Submission Date

20-05-2025

Latest Decision Or Authorization Date

15-04-2026

Processing Time Days

330

Number Of Sites

10

Number Of Participants

29

Primary sponsor

Full Name

Maia Biotechnology Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Nova-Clin Medical Research Center S.R.L.

Responsibilities

CRO for Romania, Bulgaria (sponsorDuties code 15); additional duties codes: 1,12,2,8

Name

Cromos Pharma LLC

Responsibilities

CRO for Hungary, Poland, Czech Republic (sponsorDuties code 15); additional duties codes: 1,12,2,8

Name

Avance Clinical Pty Limited

Responsibilities

Safety and Pharmacovigilance - worldwide (sponsorDuties code 15)

Third parties

• {"country":"Romania","full_name":"Nova-Clin Medical Research Center S.R.L.","duties_or_roles":"Sponsor duties codes: 1,12,15 (value: CRO for Romania, Bulgaria),2,8","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"Sponsor duties codes: 3","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Australia","full_name":"Avance Clinical Pty Limited","duties_or_roles":"Sponsor duties codes: 15 (value: Safety and Pharmacovigilance - worldwide)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"Sponsor duties codes: 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Cromos Pharma LLC","duties_or_roles":"Sponsor duties codes: 1,12,15 (value: CRO for Hungary, Poland, Czech Republic),2,8","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Advanced Clinical LLC","duties_or_roles":"Sponsor duties codes: 10,6,7","organisation_type":"Pharmaceutical company"}