ARTEMIDE-Lung-02

Participants are eligible to be included in the study only if all of the following criteria apply:

Age

1 Participant must be ≥ 18 at the time of signing the ICF.

Type of Participant and Disease Characteristics

2 Histologically or cytologically documented squamous NSCLC.

Note: Tumors with a mixed adeno-squamous histology are eligible if, per the investigator’s opinion, the tumor should be treated as a squamous tumor.

3 Stage IV mNSCLC (based on the American Joint Committee on Cancer Edition 8) not amenable to curative treatment.

4 Absence of documented tumor genomic mutation results from tests conducted as part of standard local practice in any actionable driver oncogenes for which there are locally approved targeted 1L therapies.

Note: Testing for genomic mutations is not mandated if not done as part of standard local practice.

5 WHO/ECOG performance status of 0 or 1, with no deterioration over the previous 2 weeks prior to baseline at screening and prior to randomization.

6 Minimum life expectancy of 12 weeks.

7 Provision of acceptable tumor sample, as defined in the Pathology Manual and Laboratory Manual and summarized in Section 8.8, to confirm tumor PD-L1 expression TC ≥ 1% using the VENTANA PD-L1 (SP263) Assay at a Sponsor-designated central laboratory prior to randomization. Participants with unknown PD-L1 status or TC < 1% are not eligible for the study.

Note: If PD-L1 status has already been assessed using the VENTANA PD-L1 (SP263) Assay as part of screening for another AstraZeneca study, this test result may be used if the sample requirements are met.

8 At least one lesion not previously irradiated that qualifies as a RECIST 1.1 TL at baseline and can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes, which must have short axis ≥ 15 mm) with CT or MRI and is suitable for accurate repeated measurements.

9 Adequate organ and bone marrow function as defined in Table 4:

Weight

10 Minimum body weight of 30 kg.

Sex and Contraceptive/Barrier Requirements

11 Contraceptive use by participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies; see below and Appendix G for further details.

12 Female participants of childbearing potential:

(a) Must have negative pregnancy test at screening and prior to each Day 1 administration of study intervention.

(b) If sexually active with a non-sterilized male partner, must use at least 1 highly effective method of birth control from screening to 4 months after the last dose of blinded study treatment and 6 months after last dose of chemotherapy.

(c) Non-sterilized male partners of female participants of childbearing potential must use a male condom plus spermicide (if not available, a male condom without spermicide is acceptable) from screening to 4 months after the last dose of blinded study treatment and 6 months after last dose of chemotherapy. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception.

(d) Must not breastfeed and must not donate, or retrieve for their own use, ova from screening to 4 months after the last dose of blinded study treatment and 6 months after last dose of chemotherapy.

13 Non-sterilized male participants who are sexually active with a female partner of childbearing potential:

(a) Non-sterilized male participants who are not abstinent and intend to be sexually active with a female partner of childbearing potential must use a male condom plus spermicide (if not available, a male condom without spermicide is acceptable) from screening to 4 months after the last dose of blinded study treatment and 6 months after last dose of chemotherapy. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception.

(b) Female partners (of childbearing potential) of a male participant also must use at least 1 highly effective method of contraception (see Appendix G) throughout their participation in the study, and until at least 4 months after their male partners last dose of blinded study treatment and 6 months after last dose of chemotherapy.

(c) Male participants must refrain from fathering a child or donating sperm during the study and for 4 months after the last dose of blinded study treatment and 6 months after last dose of chemotherapy.

Informed Consent

14 Capable of giving signed informed consent as described in Appendix A which includes compliance with the requirements and restrictions listed in the ICF and in this CSP.

15 Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of samples for optional genetic research that supports the Genomic Initiative (see Appendix D 2).

Other Inclusion Criteria

16 All races, gender, and ethnic groups are eligible for this study. 

Participants are excluded from the study if any of the following criteria apply:

Medical Conditions

1 As judged by the investigator, any severe or uncontrolled systemic diseases, including, but not limited to, uncontrolled hypertension, and active bleeding diseases, ongoing or active known infection; ILD (of any grade), serious chronic gastrointestinal conditions associated with diarrhea (eg, active inflammatory bowel disease), active non-infectious skin disease (including any grade rash, urticaria, dermatitis, ulceration, or psoriasis) requiring systemic treatment, psychiatric illness/social situations, substance abuse, or significant cardiac conditions which, in the investigator’s opinion, makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol.

2 History of organ transplant.

3 Active or prior documented autoimmune or inflammatory disorders requiring chronic treatment with steroids or other immunosuppressive treatment.

4 History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥ 2 years before the first dose of study intervention and of low potential risk for recurrence. Exceptions include adequately resected non-melanoma skin cancer and curatively treated in situ disease.

5 Presence of small cell and neuroendocrine histology components.

6 Persistent toxicities (CTCAE Grade ≥ 2) caused by previous anticancer therapy, excluding alopecia. Participants may be enrolled with the following chronic, stable Grade 2 toxicities (defined as no worsening to > Grade 2 for at least 3 months prior to the first dose of study intervention and managed with SoC treatment) which the investigator deems related to previous anticancer therapy:

(a) Chemotherapy-induced neuropathy.

(b) Fatigue.

(c) Vitiligo.

(d) Endocrine disorders, that are controlled with replacement hormone therapy.

(e) Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study intervention in the opinion of the investigator may be included (eg, hearing loss).

7 Spinal cord compression.

8 Brain metastases unless asymptomatic, stable, and not requiring steroids or anticonvulsants for at least 4 weeks prior to start of study intervention. A minimum of 2 weeks must have elapsed between the end of brain radiotherapy and study enrollment. Participants must have recovered from the acute toxic effect of radiotherapy (eg, dizziness and signs of increased intracranial pressure).

9 Active primary immunodeficiency/active infectious disease(s):

• Known active hepatitis A, chronic or active hepatitis B, or chronic or active hepatitis C infection:

- Participants who have chronic HBV and are receiving suppressive antiviral therapy are allowed to be enrolled if viral load is controlled and ALT is normal. Those with ALT < 3 × ULN (in presence of liver metastases), not attributable to HBV infection and with controlled viral load could be enrolled. Controlled hepatitis B viral load is defined as serum HBV DNA < 100 U/mL by PCR. Participants with controlled hepatitis B viral load must remain on antiviral therapy, per institutional practice, during the study treatment and follow-up period to ensure adequate viral suppression.

- Participants who have chronic HCV are allowed to be enrolled if ALT is normal and HCV RNA undetectable by PCR, either spontaneously or in response to a successful prior course of anti-hepatitis C therapy (Regev et al 2020). Controlled hepatitis C viral load is defined as undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-hepatitis C therapy.

• Known HIV infection that is not well controlled. All of the following criteria are required to define an HIV infection that is well controlled: undetectable viral RNA load, CD4+ count of ≥ 350 cells/μL, no history of AIDS-defining opportunistic infection within the past 12 months, and stable for at least 4 weeks on the same anti-HIV medications.

10 Active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice).

11 History of clinically significant arrhythmia, cardiomyopathy of any etiology;

symptomatic congestive heart failure (as defined by New York Heart Association class ≥ 3), history of myocardial infarction within the past 6 months.

12 Medical contraindication to platinum-based doublet chemotherapy.

Prior/Concomitant Therapy

13 Any concomitant medication known to be associated with Torsades de pointes.

14 Any prior systemic therapy received for advanced or mNSCLC.

Note: Prior systemic therapy in the neoadjuvant or adjuvant setting and/or definitive radio- or chemoradiotherapy for early-stage resectable disease are allowed, provided that recurrence or progression has occurred > 12 months after the end of treatment.

15 Any prior exposure to an anti-TIGIT therapy or any other anticancer therapy targeting immune-regulatory receptors or mechanisms.

16 Any prior treatment with an anti-PD-1 or anti-PD-L1 agent.

17 Any concurrent chemotherapy, radiotherapy, immunotherapy, investigational, or biologic or hormonal therapy for cancer treatment other than those under investigation in this study. Concurrent use of hormonal therapy for non-cancer-related conditions (eg, insulin for diabetes, HRT, gonadotropin-releasing hormone analogs, and bisphosphonates) is acceptable.

18 Palliative radiotherapy with a limited field of radiation within 2 weeks or with a wide field of radiation or to more than 30% of the bone marrow within 4 weeks, prior to the first dose of study intervention.

Note: Local treatment of isolated lesions for palliative intent is acceptable

19 Major surgical procedure (excluding placement of vascular access) or significant traumatic injury within 4 weeks of the first dose of study intervention or an anticipated need for major surgery during the study.

Note: Local surgery of isolated lesions for palliative intent is acceptable.

20 Current or prior use of immunosuppressive medication within 14 days before the first dose of study intervention is excluded. The following are exceptions to this criterion (see Appendix I):

(a) Intranasal, inhaled, topical steroids, or local steroid injections (eg, intraarticular injection).

(b) Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication), as premedication for chemotherapy, or a single dose for palliative purpose (eg, pain control).

(c) Systemic corticosteroids at physiological doses not to exceed 10 mg/day of prednisone or 2 mg/day of dexamethasone or equivalent (except for the treatment of adverse events)

21 Herbal or natural products intended as treatment or prophylaxis for any type of cancer that may interfere with the activity of the study intervention are excluded, see Appendix I.

22 Receipt of live attenuated vaccine within 30 days prior to the first dose of study intervention.

Note: Participants, if enrolled, should not receive live vaccine while receiving study intervention and up to 30 days after the last dose of study intervention. See Appendix I for additional details.

Prior/Concurrent Clinical Study Experience

23 Participation in another clinical study with a study intervention or investigational medicinal device administered in the last 12 months or the combination/comparator agent (unless the safety profile is known prior to randomization), or concurrent enrollment in another clinical study (unless the study is observational [non-interventional], or the participant is in the follow-up period of an interventional study).

24 Participants with a known hypersensitivity to study intervention or any excipients of the products.

Other Exclusions

25 Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).

26 Judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements.

27 Previous enrollment in the present study.

28 For females only: Currently pregnant (confirmed with positive pregnancy test) or breast-feeding, or who are planning to become pregnant.

29 Female participants should refrain from breastfeeding from screening throughout the study and until 4 months after last dose of blinded study treatment and 6 months after last dose of chemotherapy. 

Research Nurse: Jessica Westney (x3766) Sirjana.Davkota@lthtr.nhs.uk

Administrator: Zahir Shah / Nathan Fish (x8475)