AFNT-211 for Solid Tumors

Recruiting at 11 trial locations

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

100 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is open to adult patients with solid tumors who have a KRAS G12V mutation. This mutation is often found in non-small cell lung cancer (NSCLC), colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC) and other cancers. The study is for patients whose cancer has spread through the body and for whom previous treatments were not successful or treatment does not exist. Patients must also be positive for HLA-A\*11:01. The purpose of this study is to find the best dose of AFNT-211 that is safe and can shrink tumors in patients. AFNT-211 is an investigational therapy and this is the first time that AFNT-211 is being administered to patients. AFNT-211 is an autologous T cell product which means that it is made from a patient's own T cells. These cells are engineered and grown to recognize the KRAS G12V protein on the cell surface of cancer cells. AFNT-211 is infused into patients after a short course of lymphodepleting chemotherapy. Patients will frequently visit the study site. The doctors there will regularly check the size of the cancer and the patient's health. They will also take note of any unwanted effects. Patients may continue in this study for as long as they benefit from the treatment.

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.

What data supports the effectiveness of the drug AFNT-211 for solid tumors?

The research shows that afatinib, a component of AFNT-211, has been studied in combination with other drugs like paclitaxel and bevacizumab in patients with advanced solid tumors, suggesting potential effectiveness in this context. ^{1 2 3 4 5}

How is the drug AFNT-211 different from other treatments for solid tumors?

AFNT-211 is unique because it uses astatine-211, an alpha-particle-emitting radionuclide, which allows for targeted radiotherapy that can deliver high doses of radiation directly to tumor cells while minimizing damage to surrounding healthy tissue. This approach is promising for treating solid tumors, as it combines the precision of molecular targeting with the potent effects of alpha radiation. ^{2 6 7 8 9}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Phase I study of afatinib combined with nintedanib in patients with advanced solid tumours. [2018]

2. United States 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. [2021]

3. Netherlands 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. [2018]

4. Germany pubmed.ncbi.nlm.nih.gov

A phase I study of afatinib combined with paclitaxel and bevacizumab in patients with advanced solid tumors. [2018]

5. England 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. [2022]

6. Germany 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. [2021]

7. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Astatine-211-labeled radiotherapeutics: an emerging approach to targeted alpha-particle radiotherapy. [2019]

8. England pubmed.ncbi.nlm.nih.gov

A kit method for the high level synthesis of [211At]MABG. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Evaluation of astatine-211-labeled octreotide as a potential radiotherapeutic agent for NSCLC treatment. [2018]