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Trifluridine

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Patients receive PolyPEPI1018 SC at 4 injection sites on days 1 and 15 and trifluridine and tipiracil hydrochloride PO BID on days 1-5 and 8-15. Treatment repeats every 28 days for up to 7 cycles in the absence of disease progression or unacceptable toxicity.

Colorectal Cancer Peptide Vaccine PolyPEPI1018

Trifluridine and Tipiracil Hydrochloride

Mojun Zhu, M.D.

This phase Ib trial studies the safety and side effects of a vaccine (PolyPEPI1018 vaccine) in combination with TAS-102 in treating patients with colorectal that has spread to other parts of the body (metastatic). PolyPEPI1018 peptide vaccine is used to immunize against proteins present on the surface of tumor cells. This vaccine can activate the body's immune cells, called T cells. T cells fight infections and can also kill cancer cells. TAS-102 may help block the formation of growths that may become cancer. Giving PolyPEPI1018 and TAS-102 may kill more tumor cells in patients with metastatic colorectal cancer.

PRIMARY OBJECTIVE I. To evaluate the safety and tolerability of multiple doses of colorectal cancer peptide vaccine PolyPEPI1018 (PolyPEPI1018) with trifluridine and tipiracil hydrochloride (TAS-102) in patients with metastatic colorectal cancer (mCRC).

SECONDARY OBJECTIVES:

I. To evaluate initial efficacy of PolyPEPI1018 with TAS-102 by evaluating progression free survival (PFS).

II. To evaluate initial efficacy of PolyPEPI1018 with TAS-102 by evaluating objective response rate (ORR).

III. To evaluate initial efficacy of PolyPEPI1018 with TAS-102 by evaluating duration of response (DoR).

IV. To evaluate initial efficacy of PolyPEPI1018 with TAS-102 by evaluating overall survival (OS).

CORRELATIVE OBJECTIVES:

I. Comparison of clinical benefit characteristics (ORR, PFS, OS or DoR) of the study with historical data of TAS-102.

II. Correlations between personal epitopes (PEPIs) identified by candidate CDx and T cell responses measured by enzyme-linked immune absorbent spot (ELISPOT).

III. To evaluate correlation between immune correlatives (T-cell responses in the blood and tumor and clinical benefit \[ORR, PFS, OS or DoR\]).

IV. To evaluate correlation between PEPIs/AGPs predicted by candidate CDx and clinical benefit (ORR, PFS, OS or DoR).

V. To evaluate the immunogenicity of PolyPEPI1018 by measuring both effector and memory T cell responses, VI. To evaluate immune activity of PolyPEPI1018 at tumor level (level of tumor infiltrating lymphocytes).

VII. To identify PEPIs (Personal EPItopes capable of inducing T cell responses in an individual) and AGPs (predicted number of expressed antigens likely hit by T cells) from PolyPEPI1018 in each patient.

OUTLINE:

Patients receive PolyPEPI1018 subcutaneously (SC) at 4 injection sites on days 1 and 15 and trifluridine and tipiracil hydrochloride orally (PO) twice daily (BID) on days 1-5 and 8-15. Treatment repeats every 28 days for up to 7 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for up to 1 year.

A Vaccine (PolyPEPI1018 Vaccine) and TAS-102 for the Treatment of Metastatic Colorectal Cancer

Phase Ib Open-Label Study to Evaluate Safety, Tolerability, Immunogenicity and Efficacy of Multiple Subcutaneous Injections of PolyPEPI1018 Vaccine as an Add-on Immunotherapy to TAS-102 in Late-Stage Metastatic Colorectal Cancer Subjects

The occurrence of at least 1 Grade 4 local AE or 1 Grade 3+ systemic AE during the first cycle of treatment. Evaluable patients are patients who are eligible, consented, received at least 50% of their expected cycle 1 trifluridine and tipiracil hydrochloride treatment, and received at least one dose of the PolyPEPI1018 Vaccine. The final local or systemic AE rate point estimate and corresponding 95% confidence interval will be reported.

ORR is defined as achieving complete response (CR) or partial response (PR) while on treatment. Disease status will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. ORR will be calculated as the proportion of evaluable patients who achieve response. The final ORR point estimate and corresponding 95% confidence interval will be reported.

DoR is defined at the time from first documented response (PR or CR) via RECIST 1.1 to progression or death. DoR will be estimated using the Kaplan-Meier method. Patients who are alive and progression-free will be censored at the last follow-up date. The median DoR and corresponding 95% confidence interval will be reported.

OS will be estimated using the Kaplan-Meier method. Patients who are alive will be censored at the last follow-up date. The median OS and corresponding 95% confidence interval will be reported.

Disease status will be assessed using RECIST 1.1 criteria. PFS will be estimated using the Kaplan-Meier method. Patients who are alive and progression-free will be censored at their last disease assessment date. The median PFS and corresponding 95% confidence interval will be reported.

Spots Global Cancer Trial Database for microsatellite stable rectal carcinoma