SPEARHEAD-3 Pediatric Study

• Sponsor: Adaptimmune (Industry)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05642455
• Collaborator: (none)
• Enrollment: 20
• Locations: 4
• Arm: 1
• Anticipated Duration (Months): 179
• Patients Per Site: 5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This is a pediatric basket study to investigate the safety and efficacy of afamitresgene autoleucel in HLA-A*02 eligible and MAGE-A4 positive subjects aged 2-21 years of age with advanced cancers

Condition or Disease	Intervention/Treatment	Phase
Synovial Sarcoma; Malignant Peripheral Nerve Sheath Tumor (MPNST); Neuroblastoma; Osteosarcoma	Genetic: Afamitresgene autoleucel	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2 Open Label, Basket Study to Assess the Safety, Tolerability and Anti-Tumor Activity of Afamitresgene Autoleucel in Pediatric Subjects With MAGE-A4 Positive Tumors
• Anticipated Study Start Date: May 1, 2023
• Anticipated Primary Completion Date: Oct 1, 2026
• Anticipated Study Completion Date: Apr 1, 2038

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Afamitresgene autoleucel	Genetic: Afamitresgene autoleucel; Single infusion of afamitresgene autoleucel Dose: 1.0x109 to 10x109 transduced by a single intravenous infusion

Outcome Measures

Primary Outcome Measures

1. Evaluate safety and tolerability of afamitresgene autoleucel and determination of an optimal tolerated dose range determined by incidence, severity and duration of Treatment Emergent Adverse Events and Incidence and DLTs as assessed by Investigator. [3.5 years]

   Determination of incidence, severity and duration of adverse events Incidence of DLTs and determination of optimally tolerated dose range. AEs including serious adverse events (SAEs) Incidence, severity, and duration of the AEs of special interest Replication competent lentivirus (RCL) T-cell clonality and insertional oncogenesis (IO)

Secondary Outcome Measures

1. Efficacy: Objective response rate (ORR) assessed by investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (or by International Neuroblastoma Response Criteria [INRC] 2017 in NB subjects) [3.5 years]

   ORR is defined as incidence of complete responses or partial responses as assessed by RECIST v1.1 or INRC, 2017

2. Time to response (TTR) [3.5 years]

   For patients who are observed to respond to afamitresgene autoleucel in the time from date of infusion to achieve a partial response or complete response (TTR) is assessed

3. Duration of Response (DoR) [3.5 years]

   For patients who are observed to respond to afamitresgene autoleucel the DoR is the date of initial response (including confirmation) from date of infusion up until disease progression

4. Best overall response (BOR) [3.5 years]

   BOR is assessed by the investigator per RECIST V1.1 or INCR, 2017 (for NB subjects)

5. Progression Free Survival (PFS) [3.5 years]

   PFS is assessed by the investigator from date of infusion of ADP-A2M4 up until the date of disease progression per RECIST v1.1 or INCR, 2017 (for NB subjects) or death.

6. Overall Survival (OS) [15 years]

   OS is assessed from date of infusion of ADP-A2M4 up until the date of patient death.

7. Pharmacokinetics (PK). Characterize the in vivo cellular pharmacokinetics (PK) profile of afamitresgene autoleucel by evaluation of PBMC samples for peak persistence. [3.5 years]

   Obtain PBMC samples for the evaluation of peak persistence of afamitresgene autoleucel.

8. Development and validation of an invitro diagnostic (IVD) assay for the screening of tumor antigen expression for regulatory approval. [3.5 years]

   Retention of additional tumor tissue during Pre-Screening to enable development and validation of the MAGE-A4 antigen expression companion diagnostic (CDx) assay.

9. Invitro diagnostic (IVD) assay for screening [3.5 years]

   Development and validation of the MAGE-A4 antigen expression companion diagnostic assay

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age 2-21 years

• Body weight ≥ 10 kg

• Subject has histologically confirmed diagnosis of any one of the following cancers: (A) Synovial Sarcoma, (B) MPNST, (C) Neuroblastoma, or (D) Osteosarcoma

• Must have previously received a systemic chemotherapy

• Measurable disease according to RECIST v1.1 (or INCR, 2017 Neuroblastoma only).

• HLA-A*02 positive

• Tumor shows MAGE-A4 expression confirmed by central laboratory.

• Performance Status: ECOG 0-1 or Lansky Score ≥ 80

Exclusion Criteria:

• HLA-A02:05 in either allele; or any A02 having same protein sequence as HLA-A*02:05

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide.

• History of autoimmune or immune mediated disease

• Known central nervous system (CNS) metastases.

• Other prior malignancy that is not considered by the Investigator to be in complete remission

• Clinically significant cardiovascular disease

• Active infection with human immunodeficiency virus, hepatitis B virus, hepatitis C virus, or human T cell leukemia virus

• Pregnant or breastfeeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University	Palo Alto	California	United States	94305
2	University of Colorado	Aurora	Colorado	United States	80045,
3	Memorial Sloan Kettering Kids	New York	New York	United States	10065
4	Seattle Children's Hospital	Seattle	Washington	United States	98105

Sponsors and Collaborators

• Adaptimmune

Investigators

• Principal Investigator: Tara O'Donohue, MD, Memorial Sloan Kettering Kids

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Adaptimmune
• ClinicalTrials.gov Identifier: NCT05642455
• Other Study ID Numbers: ADP-0044-004
• First Posted: Dec 8, 2022
• Last Update Posted: Dec 8, 2022
• Last Verified: Dec 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Neuroblastoma; Osteosarcoma; Sarcoma, Synovial; Nerve Sheath Neoplasms; Neurofibrosarcoma

Study Results

No Results Posted as of Dec 8, 2022