A First-In-Human Trial of pTTL in Advanced Colorectal Cancer

NCT05908643 | Recruiting Phase 1 DMC

• 1 other identifier: Neogap-CRC-01
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

Brief Summary

This is an open-label, non-randomised FIH trial investigating the safety and tolerability of a novel ATMP, pTTL, composed of autologous tumour-draining lymph node-derived T cells stimulated in vitro with personalised cancer neoantigens. The neoantigens are selected through a process starting with next generation sequencing (NGS) of tumour material from the patient followed by selection of neoantigenic mutations using an in-house software, PIOR®. Selected neoantigen epitopes are expressed as recombinant proteins, NAG, and used to stimulate T cells to promote neoantigen-specific T cell expansion in vitro in pTTL production. pTTL is thus based on autologous cells stimulated with patient-specific neoantigens. In consequence, every pTTL product is unique and designated for use in one single individual. pTTL will be administered to patients with stage IV colorectal cancer (CRC) as a single intravenous dose.

Conditions

Colorectal Cancer

Keywords

Immunotherapy; Adoptive cell therapy; T cell therapy; Neoantigens; Autologous cell therapy

Outcome Measures

Primary Outcomes (1)

• Safety of pTTL administration, as determined by assessment of incidence and severity of adverse events (AE). Immunological AEs and AEs known to be associated with T cell therapies will be classified as AEs of special interest (AESI).

  To establish that pTTL can be administered to patients with advanced CRC without unacceptable toxicity. Adverse events (AEs) will be collected and assessed according to Common terminology criteria for AEs (CTCAE) v5.0. Special focus will be placed on immunological AEs and AEs known to be associated with T cell therapies, defined as AEs of special interest (AESI). AESI will include autoimmune reactions potentially resulting from off-target toxicity such as colitis, and immune-mediated reactions associated with immune cell activation, such as cytokine release syndrome (CRS).

  Final evaluation 6 months after pTTL therapy

Secondary Outcomes (8)

• Objective response

  Final evaluation 6 months after pTTL therapy

• Time to treatment response

  Final evaluation 6 months after pTTL therapy

• Duration of treatment response

  Final evaluation 6 months after pTTL therapy

• Time to tumour progression

  Final evaluation 6 months after pTTL therapy

• Kinetics of tumour progression/growth (compared to pre-treatment)

  Final evaluation 6 months after pTTL therapy

Other Outcomes (7)

• Biomarker analysis for evaluation of pTTL persistence

  First evaluation at 6 months after pTTL therapy, with a final evaluation at the close of the study at a maximum of 5 years after pTTL administration.

• Biomarker analysis for evaluation of pTTL tumour infiltration

  First evaluation at 6 months after pTTL therapy, with a final evaluation at the close of the study at a maximum of 5 years after pTTL administration.

• Biomarker analysis for evaluation of pTTL neoantigen specificity

  First evaluation at 6 months after pTTL therapy, with a final evaluation at the close of the study at a maximum of 5 years after pTTL administration.

Study Arms (1)

Treatment with pTTL

EXPERIMENTAL

A single dose of pTTL will be administered after pre-conditioning chemotherapy with Fludarabine (30 mg/m(2) body surface area) x 3 and Cyclophosphamide (300 mg/m(2) body surface area) x 3 on days -7 to -5. pTTL will usually be infused on day 1 (5 days after last chemotherapy) with the option of administering it on day -3 if judged preferable based on the T cell expansion kinetics during pTTL production. pTTL is administered as a fresh product directly after production. Dose escalation will be applied. Cohort 1 (1 patient): 1 million (with an accepted range of down to -5%) viable cells per kg body weight Cohort 2 (3 patients): 2.5 million (down to -5%) viable cells per kg body weight Cohort 3 (3 patients): 5 million (down to -5%) viable cells per kg body weight Cohort 4 (remaining patients): up to 1 billion viable cells

Drug: pTTL

Interventions

pTTL DRUG

pTTL is an autologous cell product for adoptive cancer immunotherapy containing in vitro expanded T cells stimulated with patient-specific tumour neoantigens derived from tumour-draining lymph nodes.

Also known as: personal tumour-trained lymphocytes

Treatment with pTTL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent.
• Adult (age ≥18 years).
• Histological or cytological confirmation of CRC.
• Verified metastatic disease (stage IV classification) and have received all possible standard of care therapies, OR further standard of care therapies are currently not considered to be in the patient's best interest, OR toxicity from previous therapy limits the choice of suitable standard of care therapy OR scheduled pause in palliative standard of care therapy as judged by the Investigator.
• Measurable disease according to RECIST1.1.
• Minimum life expectancy of 3 months from the time that the individual pTTL DP is estimated to be available (as per Investigators clinical assessment). 7. ECOG performance status 0 to 1
• Adequate hematopoietic, hepatic and renal function defined as:
• Haemoglobin≥ 95 g/L (blood transfusion not less than 21 days prior to screening),
• Absolute neutrophil count ≥ 1.0x 109/L, platelets ≥100 x 109/L
• Total bilirubin \< 1.5 x ULN (does not apply to patients with Gilberts Syndrome)
• AST and ALT ≤ 1.5 x ULN (or ≤ 5 x ULN in the presence of liver metastases)
• Serum creatinine ≤ ULN (if serum creatinine is between 1 and 1.5 x ULN, patients may be eligible provided that the calculated GFR is at least 35 mL/min using Cockcroft- Gault method).
• Albumin ≥24 g/L
• Patients of childbearing potential or their partners of childbearing potential must be willing to take the appropriate precaution to avoid pregnancy or fathering a child for the duration of Part I and Part II and practice an approved, highly effective method of birth control during treatment and for 6months after receiving pTTL.
• Approved methods of birth control include:

You may not qualify if:

• Congestive heart failure New York Heart Association (NYHA)class III or IV.
• Any severe acute or chronic medical condition that places the patient at increased risk or interferes with the interpretationof trial results (as judged by the Principal Investigators, in agreement with Sponsor's Medical Representative).
• Autoimmunity disorders which may pose a risk for patients treated with pTTL, and/or affect the outcome of the pTTL treatment, as judged by Investigator at the Treatment Site and/or the Investigator at the Recruitment and Follow-Up Site.
• in these cases a CNS MRI is required within the screening period. These patients must not have symptoms from their brain metastases or treatment thereof and must not be taking steroid medications for treatment of CNS symptoms).
• Patients are not allowed to have ongoing systemic immunosuppressive concomitant medications. Systemic immunosuppressive treatments should be completed 2 weeks prior to surgery and/or 2 weeks prior to dose. Steroid medications are allowed if they are used as substitution or are administrated topically or as inhalation steroids for asthma.
• Previous Grade 3 or greater immune-related toxicity from checkpoint modulation or other immunotherapy (unless the toxicity has resolved and the patient rechallenged with the therapy without recurrence of toxicity, in which situation the patient can be considered).
• Acute or chronic infection with hepatitis B or C or syphilis.
• HIV infection.
• Pregnancy or breast-feeding.
• Investigator considers the patient unlikely to comply with trial procedures, restrictions and requirements.
• For patients required to undergo trial-specific surgery to obtain starting material:
• Less than 3 identifiable enlarged lymph nodes on pre-surgery radiology accessible for surgical excision.
• Previous surgical removal of the primary CRC tumour (would entail a high risk surgery)
• Unable to withstand the planned surgery (including ineligibility for general anaesthesia)
• At decision to proceed to pTTL administration:

Sponsors & Collaborators

• Neogap Therapeutics AB: lead
• CTC Clinical Trial Consultants AB: collaborator
• Karolinska University Hospital: collaborator
• Region Västmanland: collaborator
• Vecura: collaborator

Study Sites (2)

Medical Unit Cell therapy and Allogeneic Stem cell Transplantation (ME CAST), and the Center for Clinical Cancer studies - Phase 1 unit, Karolinska University Hospital

Stockholm, Stockholm County, 17176, Sweden

RECRUITING

Unit for Colorectal Surgery, Dept. of Surgery, Västmanlands Sjukhus Västerås

Västerås, Västerås, 723 35, Sweden

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Maximilian Kordes, MD, PhD

  Medical Unit Cell therapy and Allogeneic Stem cell Transplantation, Karolinska University Hospital

  PRINCIPAL INVESTIGATOR

• Abbas Chabok, MD, PhD

  Unit for Colorectal Surgery, Dept. of Surgery, Västmanlands Sjukhus Västerås

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Samuel Svensson, PhD

CONTACT

+46 73 354 21 94; samuel.svensson@neogap.se

Andrea Salmén, MSE

CONTACT

+46 70 359 57 11; andrea.salmen@neogap.se

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2023
• First Posted: June 18, 2023
• Study Start: March 15, 2023
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): June 1, 2032
• Last Updated: May 29, 2025

Record last verified: 2025-05

Locations

SE (2)