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

Sponsor

Famewave Ltd. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04731467

Collaborator

Bristol-Myers Squibb (Industry)

Enrollment

Locations

Arms

35.4

Anticipated Duration (Months)

13.3

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is an open-label, multicenter, multi-dose escalation and dose expansion study in subjects with selected advanced solid tumors (Part A), advanced recurrent immune checkpoint refractory non-small cell lung cancer (NSCLC) (Part B), and metastatic pancreatic cancer (Part C) to evaluate the safety and tolerability of CM-24 in combination with nivolumab. In Part C of the study nab-paclitaxel or Nal-IRI/5FU/LV will be administered subsequent to CM24 and nivolumab.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor Non Small Cell Lung Cancer Pancreatic Cancer Ovarian Cancer Papillary Thyroid Cancer Melanoma Colorectal Adenocarcinoma	Drug: CM-24 and Nivolumab - Dose Escalation Drug: CM-24 and Nivolumab - Expansion Drug: CM-24, Nivolumab, and Nab paclitaxel - Expansion Drug: CM-24, Nivolumab, and Nal-IRI/5-FU/LV - Expansion	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Mar 19, 2021

Anticipated Primary Completion Date :

Feb 1, 2024

Anticipated Study Completion Date :

Mar 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose escalation of CM24 in combination with nivolumab	Drug: CM-24 and Nivolumab - Dose Escalation Dose escalation of CM24 with nivolumab in adult subjects with selected recurrent or metastatic solid tumors
Experimental: Expansion cohort of CM24 in combination with nivolumab	Drug: CM-24 and Nivolumab - Expansion Expansion cohort of CM24 in combination with nivolumab in adult subjects with recurrent or metastatic immune checkpoint refractory non-small cell lung cancer
Experimental: Expansion cohort of CM24 in combination with nivolumab and nab-paclitaxel	Drug: CM-24, Nivolumab, and Nab paclitaxel - Expansion Expansion cohort of CM24 in combination with nivolumab and nab-paclitaxel in adult patients with metastatic pancreatic cancer
Experimental: Expansion cohort of CM24 in combination with nivolumab and Nal-IRI/5-FU/LV	Drug: CM-24, Nivolumab, and Nal-IRI/5-FU/LV - Expansion Expansion cohort of CM24 in combination with nivolumab and Nal-IRI/5-FU/LV in adult patients with metastatic pancreatic cancer

Outcome Measures

Primary Outcome Measures

Part A: Incidence of treatment emergent adverse events [Up to 24 months]
Incidence of treatment emergent adverse events with CM-24 and nivolumab in adults with selected recurrent or metastatic solid tumors
Part B: Objective Response Rate [Up to 24 months]
Objective Response Rate when phase 2 dose of CM-24 is used in combination with nivolumab in adults with recurrent and/or metastatic non-small cell lung cancer
Part C: Objective Response Rate [Up to 24 months]
Objective Response Rate when phase 2 dose of CM-24 is used in combination with nivolumab and nab-paclitaxel or Nal-IRI/5-FU/LV in adults with metastatic pancreatic cancer

Secondary Outcome Measures

Maximum serum concentration [Cmax] [Up to 24 months]
Maximum serum concentration [Cmax] of CM24
Time of maximum concentration [Tmax] [Up to 24 months]
Time of maximum concentration [Tmax] of CM24
Area under the serum concentration curve [AUC] [Up to 24 months]
Area under the serum concentration curve [AUC] of CM24
Half life [Up to 24 months]
Half life of CM24
Drug clearance [Up to 24 months]
Drug clearance of CM24
Volume of distribution [Up to 24 months]
Volume of distribution of CM24
Serum ADA parameters [Up to 24 months]
Serum ADA parameters of CM24 as measured by percentage of patients who are positive for the presence of anti-drug antibodies
Objective Response Rate when CM24 is used in combination with nivolumab [Up to 24 months]
Disease Control Rate when CM24 is used in combination with nivolumab [Up to 24 months]
Median Duration of Response when CM24 is used in combination with nivolumab [Up to 24 months]
Median Time to Response when CM24 is used in combination with nivolumab [Up to 24 months]
Progression Free Survival when CM24 is used in combination with nivolumab [Up to 48 months]
Overall Survival when CM24 is used in combination with nivolumab [Up to 48 months]
Population pharmacokinetics when CM24 is used in combination with nivolumab as measured by the maximum plasma concentration [Cmax] [Up to 24 months]
Population pharmacokinetics when CM24 is used in combination with nivolumab as measured by the average area under the concentration curve [AUC] [Up to 24 months]
Population pharmacokinetics when CM24 is used in combination with nivolumab as measured by the median area under the concentration curve [AUC] [Up to 24 months]
Population pharmacokinetics when CM24 is used in combination with nivolumab and nab-paclitaxel or Nal-IRI/5-FU/LV as measured by the maximum plasma concentration [Cmax] [Up to 24 months]
Population pharmacokinetics when CM24 is used in combination with nivolumab and nab-paclitaxel or Nal-IRI/5-FU/LV as measured by the average area under the concentration curve [AUC] [Up to 24 months]
Population pharmacokinetics when CM24 is used in combination with nivolumab and nab-paclitaxel or Nal-IRI/5-FU/LV as measured by the median area under the concentration curve [AUC] [Up to 24 months]
Disease Control Rate when CM24 is used in combination with nivolumab and nab-paclitaxel or Nal-IRI/5-FU/LV [Up to 24 months]
Duration of Response when CM24 is used in combination with nivolumab and nab-paclitaxel or Nal-IRI/5-FU/LV [Up to 24 months]
Time to Response when CM24 is used in combination with nivolumab and nab-paclitaxel or Nal-IRI/5-FU/LV [Up to 24 months]
Progression Free Survival when CM24 is used in combination with nivolumab and nab-paclitaxel or Nal-IRI/5-FU/LV [Up to 48 months]
Overall Survival when CM24 is used in combination with nivolumab and nab-paclitaxel or Nal-IRI/5-FU/LV [Up to 48 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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 B: Subjects with histologically confirmed metastatic or locally advanced non-small cell lung cancer (NSCLC) with documented progression following anti-PD-1/PD-L1 containing therapy; Subjects must have confirmation of progression of disease that is consistent with iCPD during or within 3 months of prior anti-PD1/PDL1 with either two radiographic scans showing disease progression or documented clinical progression (e.g., worsening of symptoms); Subjects could have had a maximum of 1 prior treatment regimen;
Part C: Subjects with histologically confirmed 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). .
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.

Exclusion Criteria:

Part A: Received more than two prior systemic regimens for the metastatic disease
Part B and C: Received more than 1 prior systemic regimens for the advanced/recurrent and/or metastatic disease
History of weight loss >10% over the 2 months prior to Screening;
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;
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;

Radiation within two weeks prior to the first study treatment;
Treatment with another investigational therapy within 30 days or 5 half-lives of the drug prior to Screening, whichever is longer;
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;
Pregnant or lactating women.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	HonorHealth Research Institute	Scottsdale	Arizona	United States	85258
2	Yale University	New Haven	Connecticut	United States	06520
3	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201
4	The University of Texas M.D. Anderson Cancer Center	Houston	Texas	United States	77030
5	Rambam Health Care Campus	Haifa		Israel
6	Sheba Medical Center	Ramat Gan		Israel