AFNT-211 for Solid Tumors

Overseen By Soumit Basu

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Affini-T Therapeutics, Inc.

Must not be taking: Cytotoxic chemotherapy, Gene therapy

Disqualifiers: Autoimmune disease, Primary brain tumor, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to test AFNT-211, a new therapy derived from a patient's own T cells, to determine if it can safely shrink certain types of cancer that have spread and resisted other treatments. It focuses on solid tumors with a specific KRAS G12V mutation, commonly found in lung, colon, and pancreatic cancers. The trial is open to individuals with this mutation who have had unsuccessful treatments. Participants will receive one infusion of AFNT-211 and will be closely monitored for side effects and changes in their cancer. This trial suits those whose cancer has persisted despite other therapies and who have the specific genetic mutation and cell marker required for the treatment. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking any systemic cytotoxic chemotherapy, investigational agents, or anti-tumor drugs from previous treatments within 5 half-lives or 14 days before screening, whichever is shorter. The protocol does not specify about other medications, so it's best to discuss your current medications with the trial team.

Is there any evidence suggesting that AFNT-211 is likely to be safe for humans?

A previous study tested AFNT-211 to assess its safety for people with certain types of cancer. The study focused on patients with advanced or spreading solid tumors who have a specific genetic marker called HLA-A*11:01. AFNT-211 is a treatment made from a patient's own T cells, a type of immune cell. These cells are modified in a lab to help them recognize and attack cancer cells.

Since this treatment is new and under research, safety remains a top concern. The main goal has been to evaluate tolerance and track any side effects. As AFNT-211 is in an early testing phase, the focus is on finding a safe dose and observing patient responses. In these early tests, treatments are usually given to small groups to closely monitor any unwanted effects.

Since AFNT-211 is being administered to humans for the first time, long-term data is limited. However, the ongoing study aims to ensure safety and determine the best dose that patients can handle without major issues. Participants in the study receive close monitoring to quickly manage any side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for solid tumors, which often involves chemotherapy, radiation, or surgery, AFNT-211 is unique because it uses a targeted approach, potentially offering a new mechanism of action. While traditional treatments can be harsh and affect healthy cells, AFNT-211 is designed to selectively target tumor cells, which could minimize side effects and improve outcomes. Researchers are particularly excited about its potential to be effective across different types of solid tumors, including non-small cell lung cancer, colorectal carcinoma, and pancreatic ductal adenocarcinoma, by honing in on the specific biological pathways involved in these cancers.

What evidence suggests that AFNT-211 might be an effective treatment for solid tumors?

Research has shown that AFNT-211 could be a promising treatment for certain cancers with a specific mutation called KRAS G12V. This treatment uses a person's own immune cells, known as T cells, which are modified to attack cancer cells. In lab studies, AFNT-211 proved very effective against cancer cells with the KRAS G12V mutation. Early tests in animals also demonstrated that AFNT-211 can shrink tumors. Although this is the first time AFNT-211 is being tested in humans, the trial includes different arms to evaluate its effectiveness against cancers such as non-small cell lung cancer, colorectal cancer, pancreatic cancer, and other advanced solid tumors. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

Adults with advanced solid tumors and a specific KRAS G12V mutation can join this trial. They should have tried other treatments that didn't work or have no available treatment, be positive for HLA-A*11:01, and their cancer must be measurable by certain medical criteria. Good performance status and proper organ function are required.

Inclusion Criteria

I am fully active or can carry out light work.

My cancer has a specific KRAS mutation and I have a certain genetic marker.

My cancer is advanced, cannot be surgically removed, and has not responded to or I couldn't tolerate at least one treatment.

Exclusion Criteria

I have had treatment for an immune or inflammatory condition.

I am HIV positive.

Previous allogeneic stem cell transplantation or prior organ transplantation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepleting Chemotherapy

Participants receive a short course of lymphodepleting chemotherapy prior to T cell infusion

1-2 weeks

Treatment

Participants receive a one-time infusion of AFNT-211 and are monitored for safety

4 weeks

Frequent visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

60 months

What Are the Treatments Tested in This Trial?

Interventions

• AFNT-211

Trial Overview The study tests AFNT-211, an experimental therapy made from the patient's own T cells engineered to target the KRAS G12V protein on cancer cells. It involves lymphodepleting chemotherapy followed by infusions of AFNT-211 to determine its safety and effectiveness in shrinking tumors.

How Is the Trial Designed?

Group I: Dose Expansion: PDAC Experimental Treatment 1 Intervention

20 subjects with pancreatic ductal adenocarcinoma will be given a one-time infusion of AFNT-211 at the optimal biological dose / recommended phase 2 dose determined in the escalation portion. Subjects will be monitored for safety for 28 days.

Group II: Dose Expansion: NSCLC Experimental Treatment 1 Intervention

20 subjects with non-small cell cancer will be given a one-time infusion of AFNT-211 at the optimal biological dose / recommended phase 2 dose determined in the escalation portion. Subjects will be monitored for safety for 28 days.

Group III: Dose Expansion: CRC Experimental Treatment 1 Intervention

20 subjects with colorectal carcinoma will be given a one-time infusion of AFNT-211 at the optimal biological dose / recommended phase 2 dose determined in the escalation portion. Subjects will be monitored for safety for 28 days.

Group IV: Dose Expansion: Adv Solid Tumors Experimental Treatment 1 Intervention

20 subjects with solid tumors will be given a one-time infusion of AFNT-211 at the optimal biological dose / recommended phase 2 dose determined in the escalation portion. Subjects will be monitored for safety for 28 days.

Group V: Dose Escalation Experimental Treatment 1 Intervention

Subjects will be given a one-time infusion of AFNT-211 starting at dose level 1 and monitored for 28 days (DLT period). Each cohort will enroll 2-4 subjects at different dose levels for a total of 20 subjects in the escalation portion. The optimal biological dose and recommended phase 2 dose will be determined.

Who Is Running the Clinical Trial?

Affini-T Therapeutics, Inc.

Lead Sponsor

Trials

3

Recruited

110+

Published Research Related to This Trial

In a phase I study involving 29 patients with advanced solid tumors, the maximum tolerated dose (MTD) of afatinib combined with paclitaxel and bevacizumab was determined to be afatinib 20 mg daily, paclitaxel 80 mg/m2, and bevacizumab 7.5 mg/kg, with manageable adverse effects.

The combination treatment showed promising anti-tumor activity, with 10% of patients achieving confirmed partial responses and 52% maintaining stable disease, indicating potential efficacy for this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of afatinib combined with paclitaxel and bevacizumab in patients with advanced solid tumors. Spicer, J., Irshad, S., Ang, JE., et al.[2018]

The combination of α-particle emitting radionuclide (213)Bi-DTPA-F3 and the chemotherapy drug paclitaxel significantly enhances cytotoxicity and induces apoptosis in ovarian cancer cells, leading to better treatment outcomes compared to either treatment alone.

In a mouse model with intraperitoneal OVCAR-3 xenograft tumors, the combined therapy resulted in significantly improved survival rates, indicating its potential as an effective treatment strategy for ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced efficacy of combined 213Bi-DTPA-F3 and paclitaxel therapy of peritoneal carcinomatosis is mediated by enhanced induction of apoptosis and G2/M phase arrest. Vallon, M., Seidl, C., Blechert, B., et al.[2021]

Targeted radiotherapy using astatine-211 (211At) offers a promising method for delivering high doses of radiation directly to tumors while minimizing damage to surrounding healthy tissues, thanks to the short range of alpha-particles.

The review discusses various 211At-labeled compounds that have shown potential in preclinical studies for targeted cancer treatment, including their cytotoxicity and therapeutic efficacy in animal models, along with an update on the first clinical trial involving a 211At-labeled antibody.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Astatine-211-labeled radiotherapeutics: an emerging approach to targeted alpha-particle radiotherapy. Zalutsky, MR., Vaidyanathan, G.[2019]

In a study of 10 elderly patients with advanced refractory non-small-cell lung cancer (NSCLC) and low performance status, afatinib was found to be tolerable, with a median overall survival of 5.8 months despite a low objective response rate of 11%.

The most common side effect was grade 2 diarrhea, which led to some patients refusing to increase the dosage, suggesting that a lower starting dose of afatinib may be a safer option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and efficacy of afatinib at a low starting dosage in 10 elderly or low performance status patients with advanced refractory non-small-cell lung cancer. Kashiwabara, K., Semba, H., Fujii, S., et al.[2018]

Futibatinib, an FGFR inhibitor, was found to have manageable safety and pharmacodynamic activity in a phase I trial involving 86 patients with advanced solid tumors, with a recommended phase II dose of 20 mg once daily.

The trial showed that 5 patients had partial responses to futibatinib, particularly in those with FGFR aberrations, and 41 patients (48%) experienced stable disease, indicating potential efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I, first-in-human study of futibatinib, a highly selective, irreversible FGFR1-4 inhibitor in patients with advanced solid tumors. Bahleda, R., Meric-Bernstam, F., Goyal, L., et al.[2022]

The study identified maximum tolerated doses (MTDs) for afatinib and nintedanib, showing a manageable safety profile with common side effects like diarrhea (98%) and fatigue (64%).

In terms of efficacy, the combination treatment led to partial responses in 5 patients and stable disease in 60% of participants, indicating potential antitumor activity in patients with advanced solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of afatinib combined with nintedanib in patients with advanced solid tumours. Bahleda, R., Hollebecque, A., Varga, A., et al.[2018]

The development of [(211)At]MABG, a targeted radiotherapeutic for tumors like neuroblastoma, shows promising preclinical efficacy by specifically targeting the norepinephrine transporter.

A new synthesis method for [(211)At]MABG achieved high radiochemical yields (63% with low variability) and ensured the final product was sterile and free of impurities, making it suitable for clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A kit method for the high level synthesis of [211At]MABG. Vaidyanathan, G., Affleck, DJ., Alston, KL., et al.[2018]

In a phase I study involving 43 patients with advanced solid tumors, MEDI-573 demonstrated a favorable safety profile with no dose-limiting toxicities and only one case of treatment-related hyperglycemia.

While MEDI-573 did not lead to any partial or complete responses in the tumors, 13 out of 39 evaluable patients showed stable disease, indicating some preliminary antitumor activity in a heavily pretreated population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I dose-escalation study of MEDI-573, a bispecific, antiligand monoclonal antibody against IGFI and IGFII, in patients with advanced solid tumors. Haluska, P., Menefee, M., Plimack, ER., et al.[2021]

The study investigates the use of 211At-labeled octreotide, a somatostatin analogue, as a potential treatment for non-small cell lung cancer (NSCLC), showing higher uptake in lung tissues compared to other organs.

Preclinical results indicate that 211At-SPC-octreotide has a significantly more lethal effect on cancer cells than control treatments, suggesting it could be a promising new anticancer agent for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of astatine-211-labeled octreotide as a potential radiotherapeutic agent for NSCLC treatment. Zhao, B., Qin, S., Chai, L., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06105021

NCT06105021 | Phase I Study of Autologous CD8+ and ... The primary purpose of this study is to assess the safety and tolerability of AFNT-211 in subjects who are HLA-A*11:01 positive with advanced or metastatic ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.2543

AFNT-211: An FAS-41BB–enhanced TCR-T cell therapy ... Preclinical data demonstrated a potent and safe profile for AFNT-211 that supports clinical development in HLA-A*11:01 patients with advanced/ ...

3. meetings.asco.org meetings.asco.org/abstracts-presentations/238541

AFNT-211: A phase 1 study of autologous CD4+ and CD8+ ... AFNT-211 is designed to enhance anti-tumor activity via the following mechanisms of action as shown in preclinical models: (1) the CD8α/β coreceptor enables ...

4. clinicaltrials.med.nyu.edu clinicaltrials.med.nyu.edu/cancer/clinicaltrial/2564/phase-i-study-autologous/

Perlmutter Cancer Center - Clinical Trials This is study is testing a new medicine called AFNT-211 for patients with advanced or metastatic (cancer that has spread) that has specific genetic markers, ...

5. affinittx.com affinittx.com/press-releases/affini-t-therapeutics-presents-preclinical-data-from-its-programs-targeting-oncogenic-drivers-kras-and-tp53-at-aacr/

Affini-T Therapeutics Presents Preclinical Data from its ... Our AFNT-211 Phase 1 trial in patients with solid tumors is advancing rapidly through dose escalation and is generating encouraging clinical ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS2678

A phase I study of AFNT-211, autologous CD4+ and CD8+ ... AFNT-211 represents a novel strategy to address the immunosuppressive tumor microenvironment and improve response rate as well as duration of response in solid ...

7. asco.org asco.org/abstracts-presentations/ABSTRACT507252

A phase I study of AFNT-211, autologous CD4<sup>+< ... AFNT-211 represents a novel strategy to address the immunosuppressive tumor microenvironment and improve response rate as well as duration of response in solid ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS8650

AFNT-211: A phase 1 study of autologous CD4+ and CD8+ ... AFNT-211 represents a novel strategy to address the immunosuppressive tumor microenvironment and improve response rate and duration in solid tumors.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12207871/

KRAS mutated NSCLC: past, present, and future directions in ... AFNT-211 is a G12V based cellular therapy that uses re ... safety data with neoadjuvant alectinib in patients with stage IB-III ALK+ NSCLC.