PM14 Administered Intravenously to Patients with Advanced Solid Tumors

NCT05076396 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: PM14-A-001-172017-001118-27
• Study Type: interventional
• Target: 150
• Locations: 3 countries
• Sites: 9

Brief Summary

Despite recent advances in the treatment of solid tumors in general, advanced (metastatic) disease remains mostly incurable and there is an urgent need to develop new therapeutic options for these patients, particularly investigational drugs with novel mechanisms of action. The investigation of new combination regimens of non-crossresistant agents with acceptable-and not completely overlapping-toxicities has been a major way to improve response rate and outcome of patients with advanced solid tumors.

Conditions

Advanced Solid Tumor

Keywords

Advanced Solid Tumor; PharmaMar; Cancer; PM14

Outcome Measures

Primary Outcomes (5)

• Patients with dose limiting toxicities

  To identify the dose limiting toxicities (DLTs), and to determine the maximun tolerated dose (MTD) and the recommended dose (RD) of PM14 administered i.v. on two days (Day 1 and Day 8) or on Day 1 only, both every three weeks (q3wk) over three hours to patients with advanced solid tumors.

  At cycle 2 (21-days cycle)

• Overall response rate

  To confirm the recommended dose (RD) determined during the Dose escalation phase, and to evaluate the antitumor activity of PM14 in terms of overall response rate (ORR), according to the Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1, and/or serum markers as appropriate, in patients with selected advanced solid tumors.

  At cycle 2 (21-days cycle)

• Overall response rate

  To confirm the recommended dose (RD) determined during the Dose escalation phase, and to evaluate the antitumor activity of PM14 in terms of overall response rate (ORR), according to the Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1, and/or serum markers as appropriate, in patients with selected advanced solid tumors.

  At cycle 4 (21-days cycle)

• Overall response rate

  To confirm the recommended dose (RD) determined during the Dose escalation phase, and to evaluate the antitumor activity of PM14 in terms of overall response rate (ORR), according to the Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1, and/or serum markers as appropriate, in patients with selected advanced solid tumors.

  At cycle 6 (21-days cycle)

• Overall response rate

  To confirm the recommended dose (RD) determined during the Dose escalation phase, and to evaluate the antitumor activity of PM14 in terms of overall response rate (ORR), according to the Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1, and/or serum markers as appropriate, in patients with selected advanced solid tumors.

  Through study completion up to Cycle 9

Secondary Outcomes (10)

• Clinical Benefit Rate

  Through study completion up to Cycle 9

• Progression-free Survival

  From the date of first infusion of study treatment to the date of first documented progression or date of death from any cause, assessed up to 72 months

• Duration of Response

  From the date of the first documentation of response to the date of first PD or further therapy or death, assessed up to 72 months

• Incidence of Treatment-Emergent Adverse Events

  From the date of first infusion of study treatment to the date of study termination, assessed up to 72 months

• Pharmacokinetic: Maximum Plasma Concentration (Cmax)

  At the end of Cycle 1 (each cycle is 21 days)

Study Arms (1)

PM14

EXPERIMENTAL

Patients will receive PM14 as an i.v. infusion in a total volume of 100 mL of 0.9% sodium chloride at the first three dose escalation levels. Thereafter, the volume of infusion can be increased to 250 mL.

Drug: PM14

Interventions

PM14 DRUG

PM14 drug product is provided as a sterile lyophilized powder for concentrate for solution for infusion with a strength of 5.0 mg of the active moiety. Patients will receive PM14 as an i.v. infusion in a total volume of 100 mL of 0.9% sodium chloride at the first three dose escalation levels. Thereafter, the volume of infusion can be increased to 250 mL.

PM14

Eligibility Criteria

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

You may qualify if:

• Voluntarily signed and dated written informed consent (IC), obtained prior to any specific study procedure.
• Age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1
• For the Dose escalation phase:
• Patients with pathologically confirmed diagnosis of advanced solid tumors for whom no curative standard therapy exists.
• For the Expansion phase:
• Patients with pathologically confirmed diagnosis of one of the following malignancies, for whom the standard of care therapies have failed, or are intolerant to standard of care therapies that are known to provide clinical benefit:
• Gastrointestinal tumors: colorectal cancer, gastric cancer.
• Sarcomas: liposarcoma, leiomyosarcoma, synovial sarcoma, Ewing's sarcoma.
• Tumors with deleterious germline BRCA mutation: epithelial ovarian cancer (including primary peritoneal and fallopian tube cancer), breast cancer, pancreatic cancer, prostate cancer, or any other malignancies.
• Epithelial ovarian cancer (including primary peritoneal and fallopian tube cancer) with no deleterious germline BRCA mutations or with unknown BRCA status.
• Adrenocortical carcinoma.
• Patients included in the Expansion phase need to meet the following requirements regarding the maximum number of prior chemotherapy regimens (no limit for biological therapies):
• Gastrointestinal tumors: no more than three prior chemotherapy lines for colorectal cancer; and no more than two prior chemotherapy lines for gastric cancer.
• Sarcomas: no more than two prior chemotherapy lines for liposarcoma, leiomyosarcoma and synovial sarcoma; and no more than three prior chemotherapy lines for Ewing's sarcoma.

You may not qualify if:

• Concomitant diseases/conditions:
• Increased cardiac risk:
• Uncontrolled arterial hypertension despite optimal management (≥160/100 mmHg).
• Presence of clinically relevant valvular disease.
• History of long QT syndrome.
• Corrected QT interval (QTcF, Fridericia correction) ≥450 msec on screening electrocardiogram (ECG).
• History of ischemic heart disease, including myocardial infarction, angina, coronary arteriography or cardiac stress testing with findings consistent with coronary occlusion or infarction ≤6 months prior to study entry.
• History of heart failure or left ventricular dysfunction (left ventricular ejection fraction \[LVEF\] below normal values) by multiple-gated acquisition scan (MUGA) or echocardiography (ECHO).
• ECG abnormalities, including any of the following: left bundle branch block, right bundle branch block with left anterior hemiblock, second (Mobitz II) or third degree atrioventricular block.
• Clinically significant resting bradycardia (\<50 beats per minute).
• Concomitant medication with risk of inducing torsades de pointes, which cannot be discontinued or switched to an alternative drug prior to start PM14 dosing.
• Use of a cardiac pacemaker.
• Active infection requiring systemic treatment.
• Known human immunodeficiency virus (HIV) or known hepatitis C virus (HCV) infection or active hepatitis B.
• Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the patient's participation in this study (e.g., COVID-19).

Sponsors & Collaborators

• PharmaMar: lead

Study Sites (9)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Gustave Roussy

Villejuif, París, 94805, France

RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, Catalonia, 08035, Spain

RECRUITING

Hospital General Universitario Gregorio Marañón

Madrid, Madrid, 28007, Spain

RECRUITING

Clinica Universidad de Navarra

Madrid, Madrid, 28027, Spain

RECRUITING

Hospital Universitario Fundación Jiménez Díaz

Madrid, Madrid, 28040, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, Madrid, 28041, Spain

RECRUITING

Hospital Universitario Madrid Sanchinarro

Madrid, Madrid, 28050, Spain

RECRUITING

MeSH Terms

Conditions

Neoplasms

Central Study Contacts

Carmen Kahatt, MD, PhD

CONTACT

0034 91 823 4615; ckahatt@pharmamar.com

Cristian Fernández, M.D.

CONTACT

0034 91 846 6077; cmfernandez@pharmamar.com

Study Design

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

Model Details: First-in-human, open-label, dose-finding, phase I trial, using a classical 3+3 design followed by a continual reassessment method (CRM)

Study Record Dates

• First Submitted: July 2, 2021
• First Posted: October 13, 2021
• Study Start: September 6, 2017
• Primary Completion: August 13, 2025
• Study Completion: August 13, 2025
• Last Updated: December 17, 2024

Record last verified: 2024-12

Locations

US (2); FR (1); ES (6)