First-in-Human Trial of DS-2243a in Participants With Advanced Solid Tumors

Daiichi Sankyo

Status and phase: Enrolling; Phase 1

Conditions: Sarcoma; Solid Tumors

Treatments: Drug: DS-2243a

Study type: Interventional

Funder types: Industry

Identifiers

NCT06644755

DS2243-054

Details and patient eligibility

About

This 2-part study will evaluate safety, tolerability, and clinical efficacy of DS-2243a as a treatment for participants with advanced solid tumors.

Full description

This is a global, multicenter, open-label, first-in-human, Phase 1 trial of DS-2243a as a treatment for locally advanced or metastatic synovial sarcoma (SS), myxoid/round cell liposarcoma (MRCLS), squamous cell carcinoma type non-small cell lung cancer (Sq-NSCLC), adenocarcinoma type non-small cell lung cancer (Ad-NSCLC), or urothelial carcinoma (UC) participants with HLA-A2 and/or NY-ESO positive. The trial consists of 2 parts: the Dose Escalation Part (Part 1) and the Dose Expansion Part (Part 2).

Enrollment: 150 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

1. Sign and date the main ICF.

2. Adults ≥18 years at the time the main ICF is signed.

3. Histologically or cytologically documented, advanced (metastatic or unresectable) SS or MRCLS as well as metastatic or unresectable locally advanced NSCLC (Ad/Sq) or UC.

4. Relapsed from, refractory to, or intolerant to appropriate therapies (eg, SOC therapy) to provide clinical benefit for their condition as assessed by their physician and/or investigator.

5. HLA-A*02:01, 02:02, 02:03, 02:04, 02:05, 02:06, 02:09, 02:10, or 02:11 positive.

6. Has measurable disease based on RECIST v1.1 on CT/MRI.

7. Is willing and able to provide adequate pre-treatment or archival tumor tissue sample.

8. Has ECOG PS score of 0 or 1 at Screening.

   Additional Inclusion Criterion for Part 1 (Dose Escalation)

9. Participants with NSCLC or UC: NY-ESO protein expression in tumor tissue is tested and confirmed by an IHC assay in a central laboratory.

Additional Inclusion Criterion for Part 2 (Dose Expansion) 10. NY-ESO protein expression in tumor tissue is tested and confirmed by an IHC assay in a central laboratory.

Key Exclusion Criteria:

1. Has received prior therapy targeting NY-ESO-1.

2. Has an inadequate treatment washout period prior to the start of trial intervention, defined as follows:

   1. Radiation therapy: <4 weeks (or <2 weeks if palliative radiation therapy without abdominal/pelvic radiation)
   2. Chemotherapy, antibody-based anticancer therapy, immunotherapy: <3 weeks
   3. Small molecules (eg, tyrosine kinase inhibitors): <2 weeks or 5 half-lives, whichever is longer

3. Has known symptomatic CNS metastases, leptomeningeal disease, or cord compression.

   Note: Asymptomatic or adequately treated CNS metastases are not exclusionary provided that, in the opinion of the investigator, the participant is neurologically stable.

   MRI/CT of the brain is required for all participants during Screening Period

4. Uncontrolled or clinically significant cardiovascular disease, including the following:

   1. Myocardial infarction within 6 months prior to screening
   2. Uncontrolled angina pectoris within 6 months prior to screening
   3. NYHA Class III or IV congestive heart failure
   4. LVEF ≤40% or lower than the institutional lower limit of normal
   5. QTcF interval >480 ms

5. Chronic steroid treatment (IV or oral) or any other immunosuppressive medication (ie, prednisone >10 mg QD or the equivalent).

6. Has active other primary malignancies.

7. Has unresolved toxicities from previous anticancer treatment, defined as toxicities (other than alopecia) not yet resolved to NCI-CTCAE v5.0, Grade ≤1 or baseline. Note: Participants with chronic, stable Grade 2 toxicities (defined as no worsening for 1 month prior to enrollment and managed with SOC treatment) that the investigator deems related to previous anticancer treatment may be enrolled. Such toxicities may include the following:

   1. Chemotherapy-induced neuropathy
   2. Residual toxicities from prior immuno-oncology treatment:

   Grade 2 endocrinopathies (hypothyroidism, hyperthyroidism, adrenal insufficiency, hyperglycemia due to type 1 diabetes mellitus) with adequate therapy Grade 2 skin hypopigmentation (vitiligo)

8. Has known hypersensitivity to biological agents

9. Has a history of or active autoimmune disease.

   Note: Participants with the following examples may be enrolled as an exception:

   1. Type I diabetes mellitus/hypothyroidism only requires hormone replacement.
   2. Skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment.

10. Has HIV infection. Participants must be tested for HIV viral load during the Screening Period if acceptable by local regulations or IRBs/IECs.

    Note: For Part 2 only, the following participants will be eligible:

    1. Have CD4+ T-cell count ≥350 cells/mm3 at the time of screening.
    2. Have virologic suppression, defined as confirmed HIV RNA level below 50 or the lower limit of quantitation (below the limit of detection) at the time of screening and for at least 12 weeks before screening.
    3. Have no acquired immunodeficiency syndrome-defining opportunistic infections or conditions within the past 12 months.
    4. Are on stable antiretroviral therapy regimen, without changes in drugs or dose modification, for at least 4 weeks before trial entry (Day 1) and agree to continue antiretroviral therapy throughout the trial, as defined per institutional protocol.

11. Has active or uncontrolled hepatitis B or C infection as defined per institutional guidelines.

    Note: For Part 2 only, the following participants will be eligible:

    1. HBsAg-positive participants are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to allocation (participants should remain on antiviral therapy throughout study intervention and follow local guidelines for HBV antiviral therapy after completion of study intervention).
    2. Have a history of hepatitis C infection and HCV viral load is below the level of detection in the absence of antiviral therapy during the previous 4 weeks.
    3. Have normal transaminase values, or, if liver metastases are present, abnormal transaminases with a result of AST/ALT <3 × ULN, which are not attributable to HCV infection.

12. Female who is pregnant or breastfeeding or intends to become pregnant during the trial.

13. Any previous, current, or uncontrolled clinically relevant illness, medical condition, psychological condition, surgical history, physical finding, or laboratory abnormality that, in the investigator's opinion, could affect the safety of the participant; alter the absorption, distribution, metabolism or excretion of the trial intervention; or confound the assessment of trial results.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

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150 participants in 5 patient groups

Part 1: Dose Escalation DS-2243a

Experimental group

Description:

Participants will receive DS-2243a at escalating doses. The recommended dose for expansion (RDE) will be calculated using data collected from this population.

Treatment:

Drug: DS-2243a

Part 2: Dose Expansion SS/MRCLS

Experimental group

Description:

Participants with synovial sarcoma or myxoid/round cell liposarcoma will receive DS-2243a at the recommended dose for expansion (RDE)

Treatment:

Drug: DS-2243a

Part 2: Dose Expansion Sq-NSCLC

Experimental group

Description:

Participants with squamous cell carcinoma-non-small cell lung cancer will receive DS-2243a at the recommended dose for expansion (RDE)

Treatment:

Drug: DS-2243a

Part 2: Dose Expansion UC

Experimental group

Description:

Participants with urothelial carcinoma will receive DS-2243a at the recommended dose for expansion (RDE)

Treatment:

Drug: DS-2243a

Part 2: Dose Expansion Ad-NSCLC

Experimental group

Description:

Participants with adenocarcinoma-non-small cell lung cancer will receive DS-2243a at the recommended dose for expansion (RDE)

Treatment:

Drug: DS-2243a