A Study to Investigate LYL797 in Adults With Solid Tumors

• Sponsor: Lyell Immunopharma, Inc. (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT05274451
• Collaborator: (none)
• Enrollment: 54
• Locations: 7
• Arm: 1
• Anticipated Duration (Months): 53.1
• Patients Per Site: 7.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study will evaluate the safety and tolerability of LYL797, a ROR1-targeted CAR T-cell therapy, in patients with ROR1+ relapsed or refractory triple negative breast cancer (TNBC) or non-small cell lung cancer (NSCLC). The first part of the study will determine the safe dose for the next part of the study, and will enroll TNBC patients only. The second part of the study will test that dose in additional TNBC patients and NSCLC patients.

Condition or Disease	Intervention/Treatment	Phase
Triple Negative Breast Cancer; TNBC - Triple-Negative Breast Cancer; Non-small Cell Lung Cancer; Non Small Cell Lung Cancer; Non Small Cell Lung Cancer Metastatic; Non-Small Cell Carcinoma of Lung, TNM Stage 4; Advanced Breast Cancer; Advanced Lung Carcinoma; NSCLC; NSCLC, Recurrent; NSCLC Stage IV; Relapsed Cancer; Relapse/Recurrence; Recurrent Breast Cancer; Recurrent NSCLC	Biological: LYL797	Phase 1

Detailed Description

This Phase 1, single-arm, open-label, multi-center, dose-escalation and -expansion study will evaluate the safety and tolerability of LYL797, ROR1-targeting CAR T cells, in adults with relapsed and/or refractory ROR1+ triple negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC). The dose-escalation phase (TNBC only), and will investigate 4 dose levels to determine the recommended Phase 2 dose (RP2D). The dose-expansion phase will enroll both TNBC and NSCLC at the RP2D.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 54 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Single-arm, open-label, dose-escalation and -expansion studySingle-arm, open-label, dose-escalation and -expansion study
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1 Study to Assess the Safety and Efficacy of LYL797, ROR1-Targeting CAR T Cells, in Adults With Relapsed and/or Refractory Solid-Tumor Malignancies
• Actual Study Start Date: Mar 29, 2022
• Anticipated Primary Completion Date: Mar 1, 2025
• Anticipated Study Completion Date: Sep 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental LYL797 ROR1-targeted CAR T cells	Biological: LYL797; LYL797 is an autologous, genetically (Gen-R™) and epigenetically (Epi-R™) reprogrammed ROR1-targeted chimeric antigen receptor (CAR) T-cell therapy

Outcome Measures

Primary Outcome Measures

1. Evaluate incidence of dose-limiting toxicities (DLTs) [Up to 2 years]

   Incidence of dose-limiting toxicities (DLTs)

2. Evaluate incidence of treatment-emergent adverse events (TEAEs) [Up to 2 years]

   Incidence of treatment-emergent adverse events (TEAEs)

3. Evaluate severity of treatment-emergent adverse events (TEAEs) [Up to 2 years]

   Severity of treatment-emergent adverse events (TEAEs)

4. Determine recommended Phase 2 Dose (RP2D) [Up to 2 years]

   Dose-escalation phase to determine the recommended Phase 2 dose

Secondary Outcome Measures

1. Evaluate anti-tumor activity of LYL797 based on overall response rate (ORR) by RECIST, version 1.1 [Up to 2 years]

   Overall response rate (ORR) by RECIST, version 1.1

2. Evaluate anti-tumor activity of LYL797 based on complete response (CR) rate by RECIST, version 1.1 [Up to 2 years]

   Complete response (CR) rate by RECIST, version 1.1

3. Evaluate duration of response (DOR) [Up to 2 years]

   Duration of response (DOR)

4. Evaluate progression-free survival (PFS) [Up to 2 years]

   Progression-free survival (PFS)

5. Evaluate overall survival (OS) [Up to 2 years]

   Overall survival (OS)

6. Evaluate maximum concentration of LYL797 (Cmax) of LYL797 in peripheral blood (PB) samples [Up to 2 years]

   Maximum concentration of LYL797 (Cmax)

7. Evaluate time to Cmax (Tmax) of LYL797 in peripheral blood (PB) samples [Up to 2 years]

   Time to Cmax (Tmax)

8. Evaluate area under the concentration-time curve (AUC) of LYL797 in the peripheral blood (PB) [Up to 2 years]

   Area under the concentration-time curve (AUC)

9. Evaluate Persistence of LYL797 CAR T cells in peripheral blood samples [Up to 2 years]

   Persistence of LYL797 in PB

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• ≥ 18 years of age at time of informed consent

• Histologically confirmed TNBC or NSCLC that is relapsed or refractory, metastatic or locally advanced and unresectable that is ROR1+ by central laboratory immunohistochemistry (IHC)

• Measurable disease including a target lesion and an additional lesion for biopsy

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

• Adequate organ and marrow function

• Women of childbearing potential must have a negative pregnancy test at screening

• All participants must agree to practice highly effective methods of contraception

Exclusion Criteria:

• Prior treatment with any adoptive T-cell therapy or anti-ROR1 therapy

• Prior solid organ transplantation

• Active, untreated brain metastasis or leptomeningeal disease; stable, treated brain involvement by disease is allowed

• Untreated or active infection at the time of screening or leukapheresis

• HIV-positive, HTLV-1-positive, active acute or chronic HBV or HCV, or active tuberculosis

• Impaired cardiac function or clinically significant cardiac disease

• Uncontrolled pleural or pericardial effusion

• Systemic corticosteroids or other immunosuppressive medications within 14 days of leukapheresis

• Required chronic anticoagulation, such as warfarin, low molecular weight heparin, or Factor Xa inhibitors

• Pregnant or lactating/nursing women

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale New Haven Hospital	New Haven	Connecticut	United States	06510
2	Mayo Clinic	Jacksonville	Florida	United States	32224
3	Roswell Park Comprehensive Cancer Center	Buffalo	New York	United States	14203
4	Oregon Health and Science University Hospital	Portland	Oregon	United States	97239
5	Sidney Kimmel Cancer Center, Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
6	Sarah Cannon Research Institute and Tennessee Oncology	Nashville	Tennessee	United States	37203
7	Froedtert Hospital, Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226

Sponsors and Collaborators

• Lyell Immunopharma, Inc.

Investigators

• Study Director: Heidi Gillenwater, MD, Lyell Immunopharma, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Lyell Immunopharma, Inc.
• ClinicalTrials.gov Identifier: NCT05274451
• Other Study ID Numbers: LYL797-101
• First Posted: Mar 10, 2022
• Last Update Posted: Aug 1, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Lyell Immunopharma, Inc.: CAR T-cell therapy; CAR T; CAR T-cell; CAR-T; CAR-T cell therapy; CAR-T cell; ROR1; ROR1+; ROR1 positive; cell therapy; immunotherapy; relapsed; refractory; solid tumor; advanced; metastatic; breast cancer; lung cancer; triple negative breast cancer; non small cell lung cancer
• Additional relevant MeSH terms: Carcinoma; Breast Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Triple Negative Breast Neoplasms; Recurrence

Study Results

No Results Posted as of Aug 1, 2022