A Study Comparing TAK-928 With Docetaxel in Adults With Non-Small Cell Lung Cancer

Prior treatment

• History of deep venous thrombosis, pulmonary embolism, or any other serious thromboembolic events within 30 days prior to enrollment (implantable port or catheter-related thrombosis, or superficial venous thrombosis are not considered "serious" thromboembolisms). Participants with a history of a serious thromboembolic event must be asymptomatic and on stable anticoagulation therapy (if such therapy is deemed necessary by the treating physician).
• History of or current ILD; history or current presence of the following lung diseases requiring corticosteroid therapy: pulmonary fibrosis, and drug-related, immune-related or radiation pneumonitis; current active pulmonary infection requiring anti-infective therapy; active pulmonary TB within 1 year prior to enrollment; severely impaired pulmonary function, including but not limited to the following:, severe asthma or severe chronic obstructive pulmonary disease within 3 months prior to randomization; autoimmune, connective tissue, or inflammatory diseases involving the lungs (such as rheumatoid arthritis, Sjögren's disease, and sarcoidosis); previous unilateral pneumonectomy.
  • Note: Participants with a positive IGRA and negative chest imaging for active pulmonary TB (that is, participants with a history of latent TB) may enroll if they have completed appropriate definitive treatment for latent TB prior to enrollment in the trial (C1D1). Participants with a history of active TB may enroll if they have completed appropriate definitive treatment for active TB more than 1 year before enrollment in the trial (C1D1) and chest imaging at the time of screening is negative for active disease.
• Current or recent significant gastrointestinal disease or condition, including:
  • Flare of inflammatory bowel disease (within 6 months prior to the first dose of the investigational product).
  • Grade \>=2 diarrhea CTCAE V5.0 within 2 weeks prior to the first dose of the investigational product.
• Known or suspected allergy to the investigational product and any excipients. Known or suspected severe hypersensitivity reactions to docetaxel or to drugs formulated with polysorbate 80.
• Prior history of significant toxicity related to ICI administration that required permanent discontinuation of this therapy.
• Unresolved Grade \>1 toxicity related to any previous antitumor therapy (excluding alopecia, asthenia, hypothyroidism requiring only thyroid hormone replacement therapy (HRT), hyperglycemia requiring only insulin replacement therapy, adrenal insufficiency requiring physiological corticosteroid replacement, electrolyte abnormalities requiring only symptomatic treatment, and other conditions not affecting the investigational product treatment as assessed by the investigator).
• Have not adequately recovered from previous surgery or have undergone any major surgery, within 4 weeks before the first dose of investigational product.
• Serious/active/uncontrolled infection, infection requiring systemic intravenous antibiotics, or fever of unknown origin (\>=38°C) within 2 weeks before the first dose of investigational product.
• Diagnosed with other pathologically confirmed malignancies within 5 years prior to informed consent, with exception of radically treated basal cell carcinoma of skin, squamous cell carcinoma of skin, carcinoma in situ, localized prostate cancer, papillary thyroid cancer, and other radically treated malignancies with no known active disease for at least 2 years prior to enrollment and with very low risk of recurrence.
• Received any of following excluded medications or treatments:
  • Docetaxel.
  • Received more than 1 anti-PD-1/PD-L1 therapy in metastatic or recurrent unresectable locally advanced setting. Prior anti-PD-1/PD-L1 therapy in the curative locally advanced setting followed by anti-PD-1/PD-L1 therapy in the metastatic or recurrent unresectable locally advanced setting is allowed, not to exceed 2 prior lines of anti-PD-1/PD-L1 therapy in total.
  • Systemic antitumor therapy except anti-PD-1/PD-L1 therapy and platinum-based doublet chemotherapy including but not limited to targeted therapy, antibody drug conjugates, cell therapies, and other ICIs.
  • One prior line of anti-VEGF antibody administered in combination with 1L ICI and chemotherapy is allowed.
  • For participants with KRAS mutations, 1 prior line of RAS-targeted therapy is allowed.
  • Note: For Japan-specific SRI part only: The above listed 3 limitations regarding prior systemic antitumor therapy do not apply to participants enrolled in the Japan-specific SRI part.
• Interleukin (IL)-2 or IL-15 cytokines or related therapies.
• Chemotherapy within 2 weeks or 5 half-lives (whichever is longer) before the first dose of investigational product without delayed toxicity.
• Antitumor antibody therapy (excluding antibody drugs such as denosumab for the treatment of bone metastases) within 4 weeks before first dose of the investigational product.
• Palliative radiotherapy within 2 weeks prior to the first dose of investigational product.
• Live vaccine within 28 days prior to first dose of investigational product.
• Immunosuppressive or systemic corticosteroid therapy (\>10 mg/day of prednisone or equivalent) within 2 weeks prior to the first dose of investigational product.
• Received traditional Chinese medicine with potential antitumor activity or known antitumor indications within 1 week before the first dose of the investigational product.

Other illness

• Active uncontrolled bleeding, known bleeding diathesis, or significant concern for risk of acute life-threatening bleeding (for example, radiographic evidence that tumor invades large blood vessels or the investigator judges that the tumor is very likely to invade major vessels with the potential to cause fatal bleeding during the duration of the trial).
• History of severe, poorly controlled allergies, asthma or atopic dermatitis (except for atopic dermatitis caused by immunotherapy).
  • Note: remote history of childhood asthma is not exclusionary.
• Active autoimmune disease requiring systemic treatment (for example, use of disease modifying drugs, corticosteroids \>10 milligrams (mg) daily equivalent of prednisone, biologics or immunosuppressants) within 2 years before the first dose.
  • Note: Replacement therapies (for example, thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) are not considered systemic treatments and are not exclusionary.
• Known history of allogeneic organ transplantation and/or allogeneic hematopoietic stem cell transplantation.
• Psychiatric illness altered mental status, or drug abuse that prevents understanding of the informed consent process and/or completion of required trial-related evaluations.

Lab values

• (a) Squamous NSCLC: Known actionable genomic alteration, including any of the following driver gene mutations:
  • EGFR: including exon 19 deletion, exon 21 L858R, exon 20 T790M, exon 20 S768I, exon 21 L861Q, exon 18 G719X, and exon 20 insertion mutations.
  • ALK rearrangement.
  • ROS proto-oncogene 1, ROS1 rearrangement.
  • B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E mutation.
  • NTRK 1/2/3 fusion.
  • MET proto-oncogene, MET exon 14 skipping mutation.
  • RET proto-oncogene (RET) rearrangement.
  • V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (ERBB2, also known as HER2) mutation.
  • Note: (1) It is not mandatory to have undergone driver gene testing for participants with squamous NSCLC. (2) KRAS mutations are not exclusionary.
  • (b) Nonsquamous NSCLC: Must have documentation of prior testing demonstrating negative AGA status for any of the following driver gene mutations:
  • EGFR: including exon 19 deletion, exon 21 L858R, exon 20 T790M, exon 20 S768I, exon 21 L861Q, exon 18 G719X, and exon 20 insertion mutations.
  • ALK rearrangement.
  • ROS1 rearrangement.
  • Any other driver gene mutations listed here are excluded if known to be present, but routine testing for these or other known actionable genomic alterations is not required: BRAF V600E mutation; NTRK 1/2/3 fusion; MET exon 14 skipping mutation; RET rearrangement; and ERBB2, also known as HER2 mutation.
  • Note: KRAS mutations are not exclusionary.
  • (c) For Japan-specific SRI part: This criterion is not applicable for Japanese participants enrolled in the SRI part.
• Presence of any of the following hematologic abnormalities at baseline\*:
  • Hemoglobin \<9 g/dL.
  • Absolute neutrophil count (ANC) \<1,500 mm\^3.
  • PLT count \<100 x 10\^3/mm\^3. \*"Baseline" is defined as the last available observation prior to the first dose of investigational product.
• Presence of any of the following serum chemistry abnormalities at baseline:
  • Total bilirubin greater than (\>) 1.0×ULN except for participants with Gilbert's syndrome with serum bilirubin \<=3×ULN or if concurrent conjugated bilirubin \<=ULN.
  • AST or ALT \>2.5×ULN without concomitant alkaline phosphatase \>2.5×ULN or AST or ALT \>1.5×ULN with concomitant alkaline phosphatase \>2.5×ULN. For participants with liver metastases, AST or ALT \>5×ULN (alkaline phosphatase must be \<=2.5×ULN).
  • Creatinine clearance (CrCl) \<30 milliliters per minute (mL/min); the Cockcroft-Gault formula is used to calculate CrCl (using ideal body weight for obese participants and actual body weight for non-obese participants).
  • Albumin \<30 grams per liter (g/L).
• Presence of any of the following coagulation parameter abnormalities at baseline:
  • International normalized ratio (INR) \>1.5×ULN (\>3×ULN if on stable dose anticoagulation).
  • Partial thromboplastin time (PTT; or activated partial thromboplastin time \[aPTT\]) \>1.5×ULN (\>3×ULN if on stable-dose anticoagulation).
• Presence of clinically significant cardiovascular or cerebrovascular diseases, including:
  • Symptomatic, clinically unstable arrhythmia or arrhythmia requiring clinical intervention.
  • Severe conduction disorders (such as third-degree atrioventricular block and bundle branch block).
  • QT interval corrected for heart rate (QTc interval, calculated using Fridericia's formula) \>=480 msec.
  • Uncontrolled hypertension despite standard treatment.
  • History of myocarditis.
  • Left ventricular ejection fraction \<50%.
  • Congestive heart failure requiring treatment.
  • Class II to IV cardiac insufficiency according to the New York Heart Association functional classification.
  • History of acute coronary syndrome (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to the first dose of investigational product.
  • Cerebrovascular accident or transient ischemic attack within 6 months before the first dose of the investigational product.
  • History of seizures unless controlled on stable dose of antiseizure medications.
• Cardiac enzymes \>=levels consistent with acute myocardial infarction as defined by laboratory-specific criteria. Participants with isolated Grade 1 elevated cardiac enzymes require cardiology clearance and consultation with the sponsor's medical monitor to confirm absence of ongoing myocardial/ischemic disease.
• Uncontrolled human immunodeficiency virus (HIV), active syphilis, active hepatitis B virus (HBV), or hepatitis C virus (HCV).
  • Participants who are HIV-positive must have CD4 \>=350 cells per microliter (cells/µL) and must be on established highly active antiretroviral therapy (ensure no expected drug-drug interactions) for at least 4 weeks with an HIV viral load \<400 copies/mL).
  • Participants with positive results consistent with an untreated syphilis infection cannot enroll.
  • Note: Testing with either a treponemal (for example, Treponema Pallidum hemagglutination \[TPHA\] or Treponema Pallidum particle agglutination \[TPPA\] test) or nontreponemal (for example, rapid plasma reagin \[RPR\] or Venereal Disease Research Laboratory test) assay is acceptable. An initial positive test should be confirmed with an assay using the alternate testing approach (for example, treponemal followed by nontreponemal or vice versa). If the second test is negative, the participant may enroll in the trial.
  • Participants with positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) should undergo HBV DNA testing. If the HBV DNA copy number is \<=2.5×10\^3 copies/mL or \<=500 IU/mL) or below the lower limit of detection, the participant can be enrolled.
  • Participants with positive HCV serology results must have an HCV RNA viral load that is negative or below the lower limit of detection.
  • Participants who have received definitive HCV treatment and have undetectable viral load results are allowed.
• History or current evidence of any disease, treatment, or laboratory abnormality that, in the judgment of the investigator, could compromise the safety of the participant, interfere with obtaining informed consent, affect participant compliance, or affect safety evaluations of the investigational product.

Other

• Women who are pregnant or breastfeeding, or intending to become pregnant before, during, or within 6 months after the last dose of any trial intervention. WOCBP not using and/or not willing to use at least 1 form of highly effective method of contraception and 1 barrier method of contraception or fertile men with WOCBP partner(s) not using and/or not willing to use at least 1 form of acceptable contraception.
• Participants with enlarging or symptomatic brain metastases are excluded from the trial. Participants who are neurologically, clinically and radiologically stable \>=2 weeks after definitive treatment for brain metastases and/or participants with small (sum of all brain lesions: ≤3 cm), asymptomatic, incidental, untreated brain metastases may participate in this trial as long as they meet certain criteria as defined in the protocol.
• Uncontrolled third space effusion requiring repeated drainage, such as pleural effusion, abdominal effusion, or pericardial effusion.
• Uncontrolled tumor-related pain or symptomatic hypercalcemia.
• Unable to meet protocol requirements for known or foreseeable reasons per investigator judgement.

• Must be able to understand and willing to sign the written ICF and be able to comply with the visit schedule and related procedures specified in the protocol.
• Male or female participants must be at least 18 years old or the legal age of majority in their country, whichever is greater. Note: For the Japan-specific SRI part, participants must be Japanese residing in Japan.
• (a) Squamous NSCLC: Have locally unresectable advanced or metastatic histologically or cytologically confirmed squamous NSCLC. Mixed small cell carcinoma, or other pathological components are excluded.
  • (b) Nonsquamous NLSCLC: Have locally unresectable advanced or metastatic histologically or cytologically confirmed nonsquamous NSCLC. Mixed small cell carcinoma, or other pathological components are excluded.
  • (c) For Japan-specific SRI part: Have metastatic or unresectable solid tumors.
• Have had radiographic disease progression on or after prior treatment with anti-PD-1/PD-L1 therapy and platinum-based doublet chemotherapy (for example, carboplatin and paclitaxel), given either concurrently or sequentially. A total exposure of \>=6 weeks of prior anti-PD-1/PD-L1 therapy is required. Eligible participants include those that have:
  • Received platinum-based chemotherapy in combination with anti-PD-1/PD-L1 therapy as only prior line of therapy. OR
  • Received platinum-based chemotherapy and anti-PD-1/PD-L1 therapy sequentially (in either order) as the only 2 prior lines of therapy.
  • Note: (1) Participants that are ineligible to receive platinum-based doublet chemotherapy may still be eligible for trial enrollment, assuming all other criteria are met. (2) For the Japan-specific SRI part only: participants' disease must be refractory OR participants must be intolerant to indication-specific SOC treatment.
• Participants who have received prior anti-PD-1/PD-L1 therapy with curative intent for locally advanced disease are eligible if they meet either of the following criteria:
  • Received prior platinum-based chemotherapy with or without radiotherapy with maintenance anti-PD-1/PD-L1 therapy for Stage III disease and radiographic recurrence/progression within 6 months from the last dose of platinum-based chemotherapy. OR
  • Received prior peri-operative platinum-based chemotherapy with maintenance anti-PD-1/PD-L1 therapy for resectable Stage II/III and have radiographic recurrence within 6 months from the last dose of platinum-based chemotherapy.
  • Note: 1) Participants that are ineligible to receive platinum-based doublet chemotherapy may still be eligible for trial enrollment, assuming all other criteria are met.
  • (2) For the Japan-specific SRI part only: This criterion is not applicable for Japanese participants enrolled in the SRI part of the trial.
  • 6\. Provide formalin-fixed tumor tissue specimen. Fresh biopsies are preferred but archival specimens collected within 2 years before signing the informed consent form are acceptable (blocks or 10-15 unstained slides sectioned 4-5 microns in thickness, if tissue slides, they must be sectioned from blocks \<= 2 months from date of consent). FFPE blocks are preferred for submission; slides should be sent only if there is a local regulation preventing submission of the FFPE block. Ideally, the archival specimen should be collected subsequent to the most recent systemic therapy.
  • Note: For the Japan-specific SRI part only: Collection of tumor tissue specimen is not required for Japanese participants enrolled in the SRI part of the trial.
  • 7\. Have at least 1 measurable lesion (target lesion) by CT or MRI according to RECIST V1.1. Lesions that have previously received radiotherapy or intratumoral injection can only be used as measurable lesions if they show progression after treatment (either pathologically confirmed or with observation of radiographic progression more than 3 months after treatment) as per RECIST V1.1. Lesions chosen for a screening biopsy should not be designated as target lesions, unless pretreatment baseline imaging is performed at least 2 weeks after the biopsy to allow for adequate healing.
  • 8\. ECOG performance status (PS) score of 0 or 1. 9. Expected survival time \>=3 months. 10. WOCBP must take a urine or serum pregnancy test, highly sensitive tests are required where available based on region and must test negative for trial inclusion. WOCBP must agree to use at least 1 form of highly effective contraception and 1 barrier method of contraception during the entire course of treatment and for 6 months after the last dose of trial treatment. Fertile men must agree to use a condom, preferably combined with at least 1 form of acceptable contraception for any WOCBP partner(s) during the entire course of treatment and for 6 months after the last dose of trial intervention.
  • 11\. Lactating women must agree to strictly abstain from breastfeeding during the entire Treatment Period and for 6 months after the treatment.