Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

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Carcinoma, Non-Small-Cell Lung

Carcinoma

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Micronutrients

Hematinics

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Vitamins

Folic Acid

Vitamin B Complex

Chelating Agents

Trace Elements

Folinic Acid

Folate

Vitamin B9

Treatment 1 is BIW on Days 1, 4, 8, and 11 of a 3-week schedule (BIW).

Intervention: EC1456 and EC20

Treatment 2 is EC1456 QW on Days 1 and 8 of a 3-week schedule (QW).

Intervention: EC1456 and EC20

Treatment 3 is EC1456 QW on Days 1, 8, and 15 of a 3-week schedule (CWD).

Intervention: EC1456 and EC20

Treatment 4 is EC1456 QIW on Days 1, 2, 3, 4, 8, 9, 10, and 11 of a 3-week schedule (QIW).

Intervention: EC1456 and EC20

Treatment 5 is EC1456 BIW. Once a dose is determined in Part A, Part B will begin with 3-6 subjects who will receive consecutive day dosing on Days 1, 2, 8, and 9 of a 3-week schedule. If this is not tolerated, the BIW cohort will continue with dosing on Days 1, 4, 8, and 11 of a 3-week schedule.

Intervention: EC1456 and EC20

Treatment 6 is EC1456 QW on Days 1 and 8 of a 3-week schedule or CWD on Days 1, 8 and 15 of a 3-week schedule.

Intervention: EC1456 and EC20

Treatment 7 is EC1456 QIW on Days 1, 2, 3, 4, 8, 9, 10, and 11 of a 3-week schedule for at least two cycles. If the patient is eligible to continue treatment (based upon treatment response and tolerability), he/she may opt to continue on the QIW schedule or change to the Treatment 6 regimen schedule (once its MTD and schedule have been determined).

Intervention: EC1456 and EC20

EC1456 is small molecule drug conjugate of folic acid and tubulysin B hydrazide (TubBH) that specifically binds to the membrane-bound FR and gains entry into the cell via endocytosis.

EC20 is Etarfolatide, a conjugate of folic acid and a tripeptide moiety that can efficiently chelate the radioisotope 99mTechnetium (99mTc). When etarfolatide is labeled with 99mTc, the product (99mTc-etarfolatide) is able to quantify FR expressing tissues with SPECT imaging.

EC1456 and EC20

Alison Armour, MD

Phase 1A/B, multicenter, open-label, non-randomized, dose-escalation oncology study to evaluate the administration of EC1456 in advanced solid tumors. In part A, EC1456 will be dose escalated on 4 concurrently enrolling schedules. FR-positive expression on a 99mTc-etarfolatide scan is not required for inclusion in Part A.

Part B of the study will confirm the maximum tolerated dose (MTD) and the recommended Phase 2 (RP2) dose of EC1456, and evaluate the efficacy of EC1456 in NSCLC all subtype patient populations with FR-positive cancer in up to three schedules (i.e., twice weekly, once weekly, and four times weekly). FR-positive expression on a 99mTc-etarfolatide scan is required for inclusion in Part B.

Minimum length of patient participation is anticipated to be 10 weeks (two 3-week cycles followed by a 30 day follow-up period).

In part A, EC1456 will be dose escalated on 4 concurrently enrolling schedules.

Treatment 1 is EC1456 BIW on Days 1, 4, 8, and 11 of a 3-week schedule (BIW); Treatment 2 is EC1456 QW on Days 1 and 8 of a 3-week schedule (QW); Treatment 3 is EC1456 QW on Days 1, 8, and 15 of a 3-week schedule (CWD) and Treatment 4 is EC1456 QIW on Days 1, 2, 3, 4, 8, 9, 10, and 11 of a 3-week schedule (QIW).

In part B, EC1456 will be dosed on 3 concurrently enrolling schedules:

Treatment 5 is EC1456 BIW. Once a dose is determined in Part A, Part B will begin with 3-6 subjects who will receive consecutive day dosing on Days 1, 2, 8, and 9 of a 3-week schedule. If this is not tolerated, the BIW cohort will continue with dosing on Days 1, 4, 8, and 11 of a 3-week schedule; Treatment 6 is EC1456 QW on Days 1 and 8 of a 3-week schedule or CWD on Days 1, 8 and 15 of a 3-week schedule; Treatment 7 is EC1456 QIW on Days 1, 2, 3, 4, 8, 9, 10, and 11 of a 3-week schedule for at least two cycles. If the patient is eligible to continue treatment (based upon treatment response and tolerability), he/she may opt to continue on the QIW schedule or change to the Treatment 6 regimen schedule (once its MTD and schedule have been determined).

Folic Acid-Tubulysin Conjugate EC1456 In Patients With Advanced Solid Tumors

A Phase I A/B Study of the Folic Acid-Tubulysin Conjugate EC1456 In Patients With Advanced Solid Tumors

Part A - To dose escalate EC1456 dose until maximum tolerated dose (MTD) and recommended Phase 2 (RP2) dose for multiple schedules is reached.

-All patients who receive at least one dose of EC1456 will be evaluated for safety. All AEs and SAEs will be graded as per CTCAE V4.0. For each dose level, summaries of dose adjustments, adverse event rates, laboratory changes, cumulative toxicity, and dose limiting toxicity (DLT) will be analyzed. Summaries of CTCAE grades will be analyzed at each dose level and each cycle.

Part B - Response to study therapy will be calculated per RECIST v1.1 criteria for all patients treated with at least one dose of EC1456

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Folic Acid-Tubulysin Conjugate EC1456 In Patients With Advanced Solid Tumors	NCT01999738	Solid Tumors Non Small Cell ...	EC1456 and EC20	18 Years -	Endocyte
Folic Acid-Tubulysin Conjugate EC1456 In Patients With Advanced Solid Tumors	NCT01999738	Solid Tumors Non Small Cell ...	EC1456 and EC20	18 Years -	Endocyte

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