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A Phase 1b, Multicenter, 2-Part, Open-Label Study of Datopotamab Deruxtecan (Dato-DXd) in Combination with Durvalumab with or without Carboplatin in Subjects with Advanced or Metastatic Non-Small Cell Lung Cancer (TROPION-Lung04)

Phase 1b Study of Dato-DXd in Combination with Durvalumab with or without Carboplatin in Advanced or Metastatic Non-Small Cell Lung Cancer (TROPION-Lung04)

Hibi Kazushige

Astrazeneka K.K

3-1, Ofuka-cho, Kita-ku, Osaka-shi, Osaka

RD-clinical-information-Japan@astrazeneca.com

Hibi Kazushige

Astrazeneka K.K

3-1, Ofuka-cho, Kita-ku, Osaka-shi, Osaka

+81-6-4802-3533

RD-clinical-information-Japan@astrazeneca.com

Recruiting

May. 12, 2021

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

- Men or women >=20 years old in Japan, >=18 years old in the other countries on the day of signing the informed consent form (for the other countries, local regulatory requirements to consent should be followed).
- Advanced or metastatic NSCLC, histologically confirmed at diagnosis of NSCLC, documented negative test results for EGFR and ALK genomic alterations, and no known genomic alterations in ROS1, NTRK, BRAF, RET, MET, or other actionable driver kinases with approved therapies (actionable genomic alterations).
- Is not a candidate for surgical resection or chemoradiation with curative intent.
- Documentation of radiological disease progression while on or after receiving the most recent treatment regimen, if any, for advanced or metastatic NSCLC.
- Must be treatment-naive or have received only 1 prior line of systemic chemotherapy, without concomitant immune checkpoint inhibitors (ICIs) including anti- PD-1/PD-L1, anti-PD-L2, and anti-CTLA-4 for advanced or metastatic NSCLC.
- Willing and able to undergo a mandatory tumor biopsy. There is no requirement for PD-L1 protein expression for inclusion.
- Archival tumor tissue from initial diagnosis, to the extent that archival tumor tissue is available, for measurement of TROP2 expression levels or other biomarkers.
- Has adequate bone marrow reserve and organ function at baseline within 7 days prior to Cycle 1 Day 1.

- Experienced grade 3 or higher immune-related adverse events with prior immunotherapy treatment.
- Received a live vaccine within 30 days prior to the first dose of study treatment.
- Active, known, or suspected autoimmune disease.
- Has a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of Cycle 1 Day 1.
- Prior allogenic organ transplantation.
- Has a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients (including but not limited to polysorbate 80) of Dato-DXd or durvalumab, and carboplatin for participants to be enrolled in relevant cohorts.
- Uncontrolled or significant cardiac disease.
- Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms.
- History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
- Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses.
- History of another primary malignancy, (beyond NSCLC) except for:
1.Malignancy treated with curative intent and with no known active disease >=3 years before the first dose of study treatment and of low potential risk for recurrence.
2.Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
3.Adequately treated carcinoma in situ without evidence of disease.
4.Participants with a history of prostate cancer.
- Toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet improved to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 Grade <=1 or baseline.

Both

Advanced or Metastatic NSCLC

- Drug: Datopotamab deruxtecan
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle (starting DS-1062a dose of 4.0 mg/kg)
- Drug: Durvalumab
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle (fixed dose 1120 mg Q3W)
- Drug: Carboplatin
Intravenous infusion Q3W on Day 1 or Day 2 of each 21-day cycle (AUC 5)

Number of Participants With Dose-limiting Toxicities and Treatment-emergent Adverse Events (Dose Escalation) [ Time Frame: DLTs: Baseline up to Cycle 1 (Days 1 to 21); TEAEs: Baseline up to 90 days after last dose, up to approximately 30 months post-dose ]
Dose-limiting toxicities and the maximum tolerated dose (MTD) will be determined in the study population treated with DS-1062a in combination with durvalumab.

1. Objective Response Rate (Dose Escalation and Dose Expansion) [ Time Frame: Baseline up to best overall response (confirmed complete response or partial response), up to approximately 30 months post-dose ]
2. Duration of Response (Dose Escalation and Dose Expansion) [ Time Frame: From first objective response (confirmed complete response or partial response) to progressive disease or death (whichever occurs first), up to approximately 30 months post-dose ]
3. Disease Control Rate (Dose Escalation and Dose Expansion) [ Time Frame: Baseline up to objective response (confirmed complete response, partial response, or stable disease), up to 30 months post-dose ]
4. Clinical Benefit Rate (Dose Escalation and Dose Expansion) [ Time Frame: Baseline up to objective response (confirmed complete response, partial response, or stable disease of at least 180 days), up to 30 months post-dose ]
5. Progression-free Survival (Dose Escalation and Dose Expansion) [ Time Frame: Baseline up progressive disease or death (whichever occurs first), up to approximately 30 months post-dose ]
6. Time to Response (Dose Escalation and Dose Expansion) [ Time Frame: Baseline up to first objective response (confirmed complete response or partial response), up to approximately 30 months post-dose ]
7. Percentage Change in the Sum of Diameters of Measurable Tumors (Dose Escalation and Dose Expansion) [ Time Frame: Baseline up to approximately 30 months post-dose ]
8. Overall Survival (Dose Escalation and Dose Expansion) [ Time Frame: Baseline up to death (any cause), up to approximately 30 months post-dose ]
9. Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of Dato-DXd, Total anti-TROP2 antibody, and MAAA-1181a (Dose Escalation and Dose Expansion) [ Time Frame: Dato-DXd, Cycle 1 and 3: Day 1 pre-dose, 30 minutes, 3 hours, 5 hours, 7 hours post-dose and Days 2, 4, 8, and 15; Cycle 2, 4 and 8, Day 1 pre- and post-dose (each cycle is 21 days) ]
10. Pharmacokinetic Parameter Time to Maximum Plasma Concentration (Tmax) of Dato-DXd, Total anti-TROP2 antibody, and MAAA-1181a (Dose Escalation and Dose Expansion) [ Time Frame: Dato-DXd, Cycle 1 and 3: Day 1 pre-dose, 30 minutes, 3 hours, 5 hours, 7 hours post-dose and Days 2, 4, 8, and 15; Cycle 2, 4 and 8, Day 1 pre- and post-dose (each cycle is 21 days) ]
11. Pharmacokinetic Parameter Area Under the Plasma Concentration-Time Curve (AUC) of Dato-DXd, Total anti-TROP2 antibody, and MAAA-1181a (Dose Escalation and Dose Expansion) [ Time Frame: Dato-DXd, Cycle 1 and 3: Day 1 pre-dose, 30 minutes, 3 hours, 5 hours, 7 hours post-dose and Days 2, 4, 8, and 15; Cycle 2, 4 and 8, Day 1 pre- and post-dose (each cycle is 21 days) ]
Area under the plasma concentration-time curve up to last quantifiable time (AUClast) and area under the plasma concentration-time curve during dosing interval (AUCtau) will be assessed.
12. Proportion of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) [ Time Frame: Dato-DXd: Cycle 1 Day 1 and Day 8 and Cycle 2 Day 1; Durvalumab: Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle is 21 days) ]
The immunogenicity of datopotamab deruxtecan (Dato-DXd) and durvalumab will be assessed.
13. Proportion of Participants Who Have Treatment-emergent ADA [ Time Frame: Dato-DXd: Cycle 1 Day 1 and Day 8 and Cycle 2 Day 1; Durvalumab: Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle is 21 days) ]
The immunogenicity of datopotamab deruxtecan (Dato-DXd) and durvalumab will be assessed.

+81-3-3520-0111

Yes

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