Phase 2 Study of DS-1062a in Advanced or Metastatic Non-small Cell Lung Cancer with Actionable Genomic Alterations

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Daiichi Sankyo Inc.

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

25 Mar 2021 → 4 Feb 2026

Decision date (initial)

2024-07-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Daiichi Sankyo Inc

External identifiers

EU CT number

2024-511449-21-00

EudraCT number

2020-002774-27

ClinicalTrials.gov

NCT04484142

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenomic, Others, Efficacy, Pharmacokinetic, Safety

To estimate the antitumor activity of DS-1062a among subjects with advanced or metastatic NSCLC with actionable genomic alterations that has progressed on or after one or more kinase inhibitors and platinum containing therapy, and one or more lines of targeted therapy to the applicable genomic alterations in the study.

Secondary objectives 4

1. 1) To further evaluate the efficacy of DS-1062a (Duration of Response, Best percentage change in the Sum of Diameters of measurable tumors, Disease Control Rate, Clinical Benefit Rate, Program-free Survival, Time to Response, Overall Response Rate, Overall Survival).
2. 2) To further evaluate the safety of DS-1062a [treatment-emergent adverse event (TEAEs) and other safety parameters during the study].
3. 3) To assess the PK of DS-1062a (PK profile).
4. 4) To assess the immunogenicity of DS-1062a

Conditions and MedDRA coding

Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. Subjects must meet all of the following criteria to be eligible for enrollment into the study: 1. Sign and date the ICF prior to the start of any study- specific qualification procedures.
2. 2. Adults ≥18 years (if the legal age of consent is >18 years old, then follow local regulatory requirements).
3. 3. Has pathologically documented NSCLC that: a. Is stage IIIB, IIIC or stage IV NSCLC disease at the time of enrollment (based on the American Joint Committee on Cancer, Eighth Edition). b. Has one or more of the following documented activating tumor genomic alterations: EGFR, ALK, ROS1, NTRK, BRAF, MET exon 14 skipping or RET.
4. 4. Has documentation of radiographic disease progression while on or after receiving the most recent treatment regimen for advanced or metastatic NSCLC.
5. 5. Subject must meet at least the following for advanced or metastatic NSCLC: a. Has been treated with at least 1 but no more than 2 cytotoxic agentcontaining therapy in the metastatic setting (please refer section 5.1 of the Protocol) b. May have received up to one checkpoint inhibitor (CPI)-containing regimen (may be in combination with a cytotoxic agent as part of a regimen described in 5a above or as an additional CPI regimen without a cytotoxic agent); c. Has been treated with one or more lines of non-CPI targeted therapy that is locally approved for the subject's applicable genomic alteration at the time of screening; OR one or more of the agents specified in thetable in section 5.1 of Protocol
6. 6. Must undergo a mandatory pre-treatment tumor biopsy procedure OR if available, a tumor biopsy that was recently collected (within 3 months of screening) after completion of the most recent anticancer treatment regimen and that has a minimum of 10 × 4 micron sections or a tissue block equivalent of 10 × 4 micron sections may be substituted for the mandatory biopsy collected during screening. Results from this biopsy will not be used to determine eligibility for the study.
7. 7. Archival tumor tissue from initial diagnosis is required, to the extent that archival tumor tissue is available.
8. 8. Has measurable disease based on local imaging assessment using RECIST v1.1.
9. 9. Has an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 - 1 at screening.
10. 10. Within 7 days before Cycle 1 Day 1, has adequate bone marrow function defined as: a. Platelet count ≥100,000/mm3 (platelet transfusion is not allowed within 1 week prior to screening assessment). b. Hemoglobin ≥9.0 g/dL (red blood cell/plasma transfusion is not allowed within 1 week prior to screening assessment). c. Absolute neutrophil count ≥1500/mm3 (granulocyte-colony stimulating factor [G-CSF] administration is not allowed within 1 week prior to screening assessment).(See sections 6.5 and 6.7 for use of G-CSF and erythropoietin)
11. 11. Within 7 days before Cycle 1 Day 1, has: - Adequate hepatic function, defined as: ▪ Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN) or AST/ALT ≤5.0 x ULN if transferase elevation is due to liver metastases). ▪ Total bilirubin (TBL) ≤1.5 × ULN or <3.0 mg/dL in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia). OR ▪ Moderate hepatic dysfunction (a maximum of 9 subjects): TBL >1.5 × ULN and ≤3 × ULN and any AST. Note: After a maximum of 9 subjects with mild or moderate hepatic dysfunction have been enrolled, subsequent subjects with moderate hepatic dysfunction will be excluded.
12. 12. Within 7 days before Cycle 1 Day 1, has adequate renal function, including mild or moderate renal function, defined as: - Creatinine clearance ≥30 mL/min, as calculated using the Cockcroft-Gault equation.
13. 13. Has a left ventricular ejection fraction (LVEF) ≥50% by either an ECHO or MUGA scan within 28 days before Cycle 1 Day 1.
14. 14. Has adequate blood clotting function defined as international normalized ratio/prothrombin time and either partial thromboplastin or activated partial thromboplastin ≤1.5 × ULN within 7 days before enrollment.
15. 15. Has an adequate treatment washout period before Cycle 1 Day 1 defined as: -Major surgery: ≥3 weeks -Radiation therapy (curative) and palliative radiation to the chest: ≥ 4 weeks ≥ 2 weeks (palliative radiation therapy to other areas) [ie, limited field and 10 or fewer days or fractions] including whole brain radiotherapy) -Anti-cancer chemotherapy (immunotherapy [non-antibody-based therapy]), retinoid therapy: ≥2 weeks or 5 times the t1/2 of the chemotherapeutic agent, whichever is longer; ≥6 weeks for nitrosoureas or mitomycin C, ≥1 week for TKIs approved for the treatment of NSCLC - baseline CT scan should be completed after discontinuation of TKI -Antibody-based anti-cancer therapy: ≥4 weeks -Chloroquine/Hydroxychloroquine: >14 days
16. 16. Has a life expectancy ≥3 months based on investigator's opinion. Please refer to the protocol for full list of inclusion criteria.

Exclusion criteria 10

1. Subjects who meet any of the following criteria will be disqualified from entering the study: 1. 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. Subjects with clinically inactive brain metastases may be included in the study. Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment. Note: A CT or magnetic resonance imaging (MRI) scan of the brain at baseline is required for all subjects. For those subjects in whom CNS metastases are first discovered at the time of screening, the treating investigator should consider delay of study treatment to document stability of CNS metastases with repeat imaging at least 4 weeks later (in which case, repeat of all screening activity may be required).
2. 2. Has leptomeningeal carcinomatosis.
3. 3. Prior treatment with: a. Any chemotherapeutic agent targeting topoisomerase I, including ADC containing such agent. b. TROP2-targeted therapy.
4. 4. Uncontrolled or significant cardiovascular disease, including: a. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) >470 milliseconds (msec) for females or >450 msec for males (based on the average of screening triplicate 12-lead ECG determinations). b. History of myocardial infarction within 6 months prior to Cycle 1 Day 1. c. History of uncontrolled angina pectoris within 6 months prior to Cycle 1 Day 1. d. Symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV) at screening. Subjects with a history of Class II to IV CHF prior to screening, must have returned to class I CHF and have LVEF ≥50% (by either an ECHO or MUGA scan within 28 days of Cycle 1 Day 1) in order to be eligible. e. History of serious cardiac arrhythmia requiring treatment. f. LVEF <50% or institutional lower limit of normal by ECHO or MUGA scan. within 28 days before Cycle 1 Day 1. g. Uncontrolled hypertension (resting systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg) within 28 days before Cycle 1 Day 1.
5. 5. Has a history of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
6. 6. Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within 3 months of the study Cycle 1 Day 1, severe asthma, severe chronic obstructive pulmonary disease [COPD], restrictive lung disease, pleural effusion, etc.), or any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (ie, rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc.), or prior pneumonectomy.
7. 7. Clinically significant corneal disease.
8. 8. Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals. Note: Subjects with localized fungal infections of skin or nails are eligible.
9. 9. Has 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+ counts/levels >250, no history of AIDs-defining opportunistic infection within the past 12 months, and stable for at least 4 weeks on same anti-HIV retroviral medications. If an HIV infection meets the above criteria, monitoring of the subjects' viral RNA load as well as the CD4+ count levels would be important. Subjects should be tested for HIV prior to Cycle 1 Day 1 if required by local regulations or Institutional Review Board (IRB)/Ethics Committee (EC).
10. 10. Has an active or uncontrolled hepatitis B and/or hepatitis C infection,is positive for hepatitis B or C virus based on the evaluation of results of tests for hepatitis B (hepatitis B surface antigen [HBsAg], antihepatitis B surface antigen [anti-HBs], anti-hepatitis B core antibody [anti-HBc], or hepatitis B virus [HBV] DNA) and/or hepatitis C infection (as per HCV RNA) within 28 days of Cycle 1 Day 1. Please refer to the protocol for full list of exclusion criteria.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall response rate (ORR) - Defined as the proportion of subjects who achieved a Best overall response (BOR) of confirmed Complete response (CR) or confirmed Partial response (PR).

Secondary endpoints 12

1. 1) Efficacy - Duration of response (DoR) - defined as the time from the date of the first documentation of response (confirmed CR or confirmed PR) to the date of the first documentation of disease progression (PD) or death due to any cause, whichever occurs first.
2. - The best percentage change in the Sum of diameters (SoD) of measurable tumors is defined as the percentage change in the smallest SoD from all post-baseline tumor assessments, taking as reference the baseline SoD.
3. - Disease control rate (DCR) - defined as the proportion of subjects who achieved a BOR of confirmed CR, confirmed PR, or SD (stable disease).
4. - Clinical benefit rate (CBR) - defined as the proportion of subjects who achieved a BOR of confirmed CR, confirmed PR, or an SD that lasts for at least 180 days.
5. - Progression-free survival (PFS) - defined as the time from the start of study treatment to the earlier of the dates of the first documentation of PD or death due to any cause.
6. - Time to response (TTR) - defined as the time from the start of study treatment to the date of the first documentation of objective response (confirmed CR or confirmed PR) in responding subjects.
7. - Overall response rate (ORR) - defined as the proportion of subjects who achieved a BOR of confirmed CR or confirmed PR.
8. - Overall survival (OS) - defined as the time from the start of study treatment to the date of death due to any cause.
9. 2) Safety - Treatment-emergent adverse event (TEAEs), Serious adverse event (SAEs), Adverse event of special interest (AESIs), Eastern Cooperative Oncology Group performance status (ECOG PS), vital sign measurements, standard clinical laboratory parameters (hematology, serum chemistry, and urinalysis), ECG parameters, Echocardiogram/multigated acquisition (ECHO/MUGA) scan findings, and ophthalmologic findings. (cont.)
10. (cont.) AEs will be coded using the most current version of MedDRA. AEs and laboratory test results will be graded using the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0.
11. 3) PK - Plasma concentrations at each time point and PK parameters (Cmax, Tmax, AUClast, AUCtau. If data permit: AUCinf, t1/2, CL, Vss, Vz, and Kel) of DS-1062a, total anti-TROP2 antibody, and MAAA-1181a (released drug) in the full PK sampling cohort.
12. 4) Immunogenicity Antidrug-antibody (ADA) prevalence: the proportion of subjects who are ADA positive at any point in time (including pre-existing ADA at baseline and treatment-emergent ADA). ADA incidence: the proportion of subjects having treatment-emergent ADA. Titer and neutralizing antibodies will be determined when ADA is positive.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Daiichi Sankyo Inc.

Sponsor organisation

Daiichi Sankyo Inc.

Address

211 Mount Airy Road

City

Basking Ridge

Postcode

07920-2311

Country

United States

Scientific contact point

Organisation

Daiichi Sankyo Inc.

Contact name

Clinical Trial Office

Public contact point

Organisation

Daiichi Sankyo Inc.

Contact name

Clinical Trial Office

Third parties 6

Locations

3 EU/EEA countries · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 23 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications