A Study of CM24 in Combination with Nivolumab in Adults with Advanced Solid Tumors

NCT04731467 | Completed Phase 1 FDA Drug

• 1 other identifier: FW-2020-1
• Study Type: interventional
• Target: 79
• Locations: 3 countries
• Sites: 18

Brief Summary

This is an open-label, multicenter, multi-dose escalation and dose expansion study in subjects with selected advanced solid tumors (Part A) and advanced metastatic pancreatic cancer (Parts C \& D) to evaluate the safety and tolerability of CM-24 in combination with nivolumab. In Part C of the study gemcitabine/nab-paclitaxel or Nal-IRI/5-FU/LV will be administered subsequent to CM24 and nivolumab. CM24, nivolumab and gemcitabine/nab-paclitaxel or Nal-IRI/5-FU/LV are administered intravenously.

Conditions

Solid Tumor; Non Small Cell Lung Cancer; Pancreatic Cancer; Ovarian Cancer; Papillary Thyroid Cancer; Melanoma; Colorectal Adenocarcinoma

Keywords

CM24; nivolumab; Opdivo; nab-paclitaxel; Abraxane

Outcome Measures

Primary Outcomes (3)

• Part A: Incidence of treatment emergent adverse events

  Incidence of treatment emergent adverse events with CM-24 and nivolumab in adults with selected recurrent or metastatic solid tumors

  Up to 24 months

• Part C: Safety and tolerability

  Incidence of treatment emergent adverse events with CM-24 is used in combination with nivolumab and gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV in adults with advanced metastatic pancreatic cancer

  Up to 24 months

• Part D: Overall survival

  This is an exploratory randomized sub-study with the objective of estimating the efficacy of CM24 and nivolumab with chemotherapy (Nal-IRI/5-FU/LV or gemcitabine/ nab-paclitaxel) and chemotherapy only (Nal- IRI/5-FU/LV or gemcitabine/nab-paclitaxel) as measured by overall survival.

  Up to 24 months

Secondary Outcomes (24)

• Maximum serum concentration [Cmax]

  Up to 24 months

• Time of maximum concentration [Tmax]

  Up to 24 months

• Area under the serum concentration curve [AUC]

  Up to 24 months

• Half life

  Up to 24 months

• Drug clearance

  Up to 24 months

Study Arms (7)

Part A- Dose escalation of CM24 in combination with nivolumab

EXPERIMENTAL

Drug: CM-24 and Nivolumab - Dose Escalation

Part C- Expansion cohort of CM24 in combination with nivolumab, nab-paclitaxel and gemcitabine

EXPERIMENTAL

Drug: CM-24, Nivolumab, Nab paclitaxel and Gemcitabine - Expansion

Part C- Expansion cohort of CM24 in combination with nivolumab and Nal-IRI/5-FU/LV

EXPERIMENTAL

Drug: CM-24, Nivolumab, and Nal-IRI/5-FU/LV - Expansion

Part D- Expansion cohort of CM24 in combination with nivolumab, nab-paclitaxel and gemcitabine

EXPERIMENTAL

Drug: CM-24, Nivolumab, Nab paclitaxel and Gemcitabine - Expansion

Part D- Expansion cohort of CM24 in combination with nivolumab and Nal-IRI/5-FU/LV

EXPERIMENTAL

Drug: CM-24, Nivolumab, and Nal-IRI/5-FU/LV - Expansion

Part D- Expansion cohort of nivolumab in combination with nab-paclitaxel and gemcitabine

ACTIVE COMPARATOR

Drug: Nivolumab, Nab paclitaxel and Gemcitabine - Expansion

Part D- Expansion cohort of nivolumab in combination with Nal-IRI/5-FU/LV

ACTIVE COMPARATOR

Drug: Nivolumab and Nal-IRI/5-FU/LV - Expansion

Interventions

CM-24 and Nivolumab - Dose Escalation DRUG

Dose escalation of CM24 with nivolumab in adult patients with selected recurrent or metastatic solid tumors

Part A- Dose escalation of CM24 in combination with nivolumab

CM-24, Nivolumab, Nab paclitaxel and Gemcitabine - Expansion DRUG

Expansion cohort of CM24 in combination with nivolumab, nab-paclitaxel and gemcitabine in adult patients with advanced metastatic pancreatic cancer

Part C- Expansion cohort of CM24 in combination with nivolumab, nab-paclitaxel and gemcitabine; Part D- Expansion cohort of CM24 in combination with nivolumab, nab-paclitaxel and gemcitabine

CM-24, Nivolumab, and Nal-IRI/5-FU/LV - Expansion DRUG

Expansion cohort of CM24 in combination with nivolumab and Nal-IRI/5-FU/LV in adult patients with advanced metastatic pancreatic cancer

Part C- Expansion cohort of CM24 in combination with nivolumab and Nal-IRI/5-FU/LV; Part D- Expansion cohort of CM24 in combination with nivolumab and Nal-IRI/5-FU/LV

Nivolumab, Nab paclitaxel and Gemcitabine - Expansion DRUG

Expansion cohort of nivolumab in combination with nab-paclitaxel and gemcitabine in adult patients with advanced metastatic pancreatic cancer

Part D- Expansion cohort of nivolumab in combination with nab-paclitaxel and gemcitabine

Nivolumab and Nal-IRI/5-FU/LV - Expansion DRUG

Expansion cohort of nivolumab in combination with Nal-IRI/5-FU/LV in adult patients with advanced metastatic pancreatic cancer

Part D- Expansion cohort of nivolumab in combination with Nal-IRI/5-FU/LV

Eligibility Criteria

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

You may qualify if:

• Part A: Previously treated subjects with recurrent and/or metastatic NSCLC, pancreatic cancer, ovarian cancer, papillary thyroid cancer, colorectal adenocarcinoma and melanoma with documented progression/intolerance following at least one previous therapy (and not more than 2 previous regimens); Part C: Subjects with histologically confirmed advanced metastatic pancreatic adenocarcinoma as defined by NCCN Guidelines; Subjects with islet cell neoplasms are excluded; subjects with a maximum of 1 prior treatment regimen for metastatic disease excluding: nab-paclitaxel containing regimens and up to 8 weeks from last chemotherapy treatment (Arm #1); fluoropyrimidine or irinotecan containing regimens and up to 8 weeks from last chemotherapy treatment (Arm #2).
• Part C, D: Subjects with histologically confirmed advanced metastatic pancreatic adenocarcinoma as defined by NCCN Guidelines; Subjects with islet cell neoplasms are excluded.
• Parts C, D: Subjects who have progressed on or after standard of care chemotherapy with a maximum of 1 prior treatment regimen for advanced metastatic disease:
• Subjects enrolled in arm with gemcitabine/nab-paclitaxel combination should have received a fluoropyrimidine and/or irinotecan containing regimen in the first line of treatment; Prior gemcitabine containing regimen may be allowed only if completed at least 6 months prior to study enrollment.
• Arm #2: Subjects enrolled in arm with Nal-IRI/5FU/LV combination should have received a gemcitabine and/or nab-paclitaxel containing regimen in the first line of treatment; Prior irinotecan and/or fluoropyrimidine containing regimens may be allowed only if completed at least 6 months prior to study enrollment.
• Part A: Availability of an archival tumor sample prior to first treatment. Parts C, D: Fresh tumor biopsy must be obtained within 3 months prior to enrollment and after the last systemic treatment was completed.
• Must have at least 1 measurable lesion per RECIST1.1 with progressing or new tumors since last antitumor therapy;
• ECOG performance status score of 0 or 1;
• Adequate safety lab results;
• Stable brain metastases;
• WCBP (Women of Childbearing Potential) must have a negative serum pregnancy test at Screening and a negative urine pregnancy test, WCBP must agree to abstain from sex or use an adequate method of contraception, males must abstain from sex with WCBP or use an adequate method of contraception.

You may not qualify if:

• Part A: Received more than two prior systemic regimens for the metastatic disease Parts C and D: Received more than 1 prior systemic regimens for the advanced metastatic disease
• Part A: History of weight loss \>10% over the 2 months prior to Screening;
• Unresolved AEs \> Grade 1 from prior anticancer therapy.
• Concurrent malignancy requiring treatment;
• Active, untreated central nervous system (CNS) metastases;
• Subjects previously treated with an anti PD-1/PD-L1 targeting agent with history immune mediated toxicity;
• Severely immunocompromised;
• History of allergy or hypersensitivity to any of the study treatment components;
• Major surgery within 4 weeks of study administration;
• Received a live / attenuated vaccine within 30 days of first treatment
• Clinically relevant serious co-morbid medical conditions including, but not limited to:
• Active infection;
• Recent (within six months of Screening) cardiac disease, myocardial infarction, or severe or unstable angina;
• History of serious arrhythmia;
• Chronic obstructive or chronic restrictive pulmonary disease, pulmonary hypertension history of or active interstitial lung disease or pneumonitis;

Sponsors & Collaborators

• Famewave Ltd.: lead
• Bristol-Myers Squibb: collaborator

Study Sites (18)

HonorHealth Research Institute

Scottsdale, Arizona, 85258, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

The University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Rambam Health Care Campus

Haifa, Israel

Location

Sheba Medical Center

Ramat Gan, Israel

Location

Hospital Clinic Barcelona

Barcelona, Spain

Location

NEXT Oncology Barcelona

Barcelona, Spain

Location

Vall d' Hebron Institute of Oncology (VHIO)

Barcelona, Spain

Location

Clinica Universidad de Navarra

Madrid, Spain

Location

Hospital 12 Octubre

Madrid, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, Spain

Location

Hospital South Texas Accelerated Research Therapeutics (START) Madrid - CIOCC

Madrid, Spain

Location

South Texas Accelerated Research Therapeutics (START) Madrid - Hospital Fundacion Jimenez Diaz

Madrid, Spain

Location

Clinica Universidad de Navarra - Pamplona

Pamplona, Spain

Location

NEXT Oncology Madrid

Pozuelo de Alarcón, Spain

Location

Hospital Quiron Salud Valencia

Valencia, Spain

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Pancreatic Neoplasms; Ovarian Neoplasms; Thyroid Cancer, Papillary; Melanoma

Interventions

Nivolumab; Taxes

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Gonadal Disorders; Adenocarcinoma, Papillary; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Thyroid Neoplasms; Head and Neck Neoplasms; Thyroid Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Economics; Health Care Economics and Organizations

Study Officials

• Michael Schickler, PhD

  Famewave Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Parts A and C are non-randomized parts, part D is a randomized part.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2021
• First Posted: February 1, 2021
• Study Start: March 19, 2021
• Primary Completion: September 30, 2024
• Study Completion: September 30, 2024
• Last Updated: December 27, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

IL (2); ES (11); US (5)