Clinical trial NCT04731467: A Study of CM24 in Combination with Nivolumab in Adults with Advanced Solid Tumors
Official title: A Phase 1/2 Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of CM24 in Combination with Nivolumab in Adults with Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
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
Lead sponsor: Purple Biotech Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
First posted: 2021-02-01
Enrollment: 79
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. 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.
2. 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.
3. 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.
4. Must have at least 1 measurable lesion per RECIST1.1 with progressing or new tumors since last antitumor therapy;
5. ECOG performance status score of 0 or 1;
6. Adequate safety lab results;
7. Stable brain metastases;
8. 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.

Exclusion Criteria:

1. 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
2. Part A: History of weight loss \>10% over the 2 months prior to Screening;
3. Unresolved AEs \> Grade 1 from prior anticancer therapy.
4. Concurrent malignancy requiring treatment;
5. Active, untreated central nervous system (CNS) metastases;
6. Subjects previously treated with an anti PD-1/PD-L1 targeting agent with history immune mediated toxicity;
7. Severely immunocompromised;
8. History of allergy or hypersensitivity to any of the study treatment components;
9. Major surgery within 4 weeks of study administration;
10. Received a live / attenuated vaccine within 30 days of first treatment
11. 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;
    * Prior organ allograft;
    * Subjects with active, known or suspected autoimmune disease;
    * History of active or latent tuberculosis infection;
    * Positive test for HIV, HBV, or HCV;
12. Radiation within two weeks prior to the first study treatment;
13. Treatment with another investigational therapy within 30 days or 5 half-lives of the drug prior to Screening, whichever is longer;
14. Treatment with botanical preparations (e.g., herbal supplements or traditional Chinese medicines) intended for general health support or to treat the disease under study within 2 weeks prior to treatment;
15. Pregnant or lactating women.

Primary outcomes:
measure: Part A: Incidence of treatment emergent adverse events
timeFrame: Up to 24 months
measure: Part C: Safety and tolerability
timeFrame: Up to 24 months
measure: Part D: Overall survival
timeFrame: Up to 24 months
Secondary outcomes:
measure: Maximum serum concentration [Cmax]
timeFrame: Up to 24 months
measure: Time of maximum concentration [Tmax]
timeFrame: Up to 24 months
measure: Area under the serum concentration curve [AUC]
timeFrame: Up to 24 months
measure: Half life
timeFrame: Up to 24 months
measure: Drug clearance
timeFrame: Up to 24 months
measure: Volume of distribution
timeFrame: Up to 24 months
measure: Serum ADA parameters
timeFrame: Up to 24 months
measure: Objective Response Rate when CM24 is used in combination with nivolumab
timeFrame: Up to 24 months
measure: Disease Control Rate when CM24 is used in combination with nivolumab
timeFrame: Up to 24 months
measure: Median Duration of Response when CM24 is used in combination with nivolumab
timeFrame: Up to 24 months
measure: Median Time to Response when CM24 is used in combination with nivolumab
timeFrame: Up to 24 months
measure: Progression Free Survival when CM24 is used in combination with nivolumab
timeFrame: Up to 48 months
measure: Overall Survival when CM24 is used in combination with nivolumab
timeFrame: Up to 48 months
measure: Population pharmacokinetics when CM24 is used in combination with nivolumab as measured by the maximum plasma concentration [Cmax]
timeFrame: Up to 24 months
measure: Population pharmacokinetics when CM24 is used in combination with nivolumab as measured by the average area under the concentration curve [AUC]
timeFrame: Up to 24 months
measure: Population pharmacokinetics when CM24 is used in combination with nivolumab as measured by the median area under the concentration curve [AUC]
timeFrame: Up to 24 months
measure: Population pharmacokinetics when CM24 is used in combination with nivolumab and gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV as measured by the maximum plasma concentration [Cmax]
timeFrame: Up to 24 months
measure: Population pharmacokinetics when CM24 is used in combination with nivolumab and gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV as measured by the average area under the concentration curve [AUC]
timeFrame: Up to 24 months
measure: Population pharmacokinetics when CM24 is used in combination with nivolumab and gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV as measured by the median area under the concentration curve [AUC]
timeFrame: Up to 24 months
measure: Disease Control Rate when CM24 is used in combination with nivolumab and gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV
timeFrame: Up to 24 months
measure: Duration of Response when CM24 is used in combination with nivolumab and gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV
timeFrame: Up to 24 months
measure: Time to Response when CM24 is used in combination with nivolumab and gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV
timeFrame: Up to 24 months
measure: Progression Free Survival when CM24 is used in combination with nivolumab and gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV
timeFrame: Up to 48 months
measure: Overall Survival when CM24 is used in combination with nivolumab and gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV
timeFrame: Up to 48 months
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: HonorHealth Research Institute
state: Arizona
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Houston
country: United States
facility: The University of Texas M.D. Anderson Cancer Center
state: Texas
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Barcelona
country: Spain
facility: Hospital Clinic Barcelona
city: Barcelona
country: Spain
facility: NEXT Oncology Barcelona
city: Barcelona
country: Spain
facility: Vall d' Hebron Institute of Oncology (VHIO)
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra
city: Madrid
country: Spain
facility: Hospital 12 Octubre
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital South Texas Accelerated Research Therapeutics (START) Madrid - CIOCC
city: Madrid
country: Spain
facility: South Texas Accelerated Research Therapeutics (START) Madrid - Hospital Fundacion Jimenez Diaz
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra - Pamplona
city: Pozuelo de Alarcon
country: Spain
facility: NEXT Oncology Madrid
city: Valencia
country: Spain
facility: Hospital Quiron Salud Valencia
Study officials:
affiliation: Famewave Ltd.
name: Michael Schickler, PhD
role: STUDY_DIRECTOR
References: