Young adults face rising cancer rates; new therapies emerge

According to surgeons at Yale Medicine, rates of colorectal and anal cancers have been rising in young adults.

Additionally, there are alarming reports of increasing HIV diagnoses worldwide, which is linked to higher anal cancer mortality for women. Improved access to testing led to a 4.2 percent increase in HIV diagnoses in the EU and a 120 percent increase in Montreal.

As these types of cancers affect younger populations and pose increased risks for those with HIV, biotech companies are striving to improve treatments. Companies involved include Oncolytics Biotech Inc., TScan Therapeutics, Inc., Bristol-Myers Squibb Company, PDS Biotechnology Corporation, and C4 Therapeutics, Inc.

 Among the promising methods of tackling the issue is the field of immunotherapies that help the body's immune system fight diseases, including cancer. One immunotherapy gaining traction is pelareorep, the flagship asset of Oncolytics Biotech Inc., which received its second FDA fast-track designation 14 months ago.

 Oncolytics recently announced an enrollment expansion of its anal cancer cohort for its GOBLET study, evaluating pelareorep in combination with atezolizumab (Tecentriq) in patients with second-line or later unresectable squamous cell carcinoma of the anal canal (SCCA).

This expansion follows positive data from Stage 1 of the study presented last year at the International Multidisciplinary Anal Cancer Conference (IMACC).

Pelareorep combined with atezolizumab showed promising results in treating anal cancer, achieving a 37.5 percent response rate and good tolerability, significantly better than the 10-14 percent response rates seen with traditional checkpoint inhibitor therapy.

“One of the most difficult challenges in my practice is the limited number of treatment options available for patients with advanced anal cancer who have progressed on first-line therapy,” said Dirk Arnold, director of Asklepios Tumorzentrum Hamburg and primary investigator of the GOBLET trial.

“I am enthusiastic about the expansion of this cohort because it will enable the continued evaluation of the pelareorep/atezolizumab combination and could provide important confirmatory data that may lead to better treatment options for patients with this late-stage disease.”

 Oncolytics plans to build on the oncology community's enthusiastic response to the IMACC 2023 data with this enrollment expansion and add new sites to the study.

After reviewing the clinical trial results, Oncolytics believes that a modest expansion of fewer than 20 patients will be sufficient to solidify the efficacy signal seen to date on the road to a future registrational study in this population.

 “There is currently no established standard therapy for patients with anal carcinoma who have failed first-line treatment,” said Matt Coffey, president, and CEO of Oncolytics.

“Continued positive results could potentially expand the opportunity for pelareorep beyond the lead indications of breast cancer and pancreatic cancer and open the door to a rapid regulatory pathway in this rare and significantly underserved patient population.”

Another therapy under clinical development is TSC-200-A0201 from TScan Therapeutics, Inc., currently in Phase I for anal cancer. TSC-200-A0201 targets HPV16 on HLA type A*02:01.

This form of cellular therapy is being tested in a basket study across multiple solid tumors. The company announced its 2024 clinical pipeline plans at the beginning of the year.

“We have now cleared INDs for four [T cell receptors] (TCRs), including TCRs for PRAME, HPV16, and MAGE-A1, and have regulatory clearance to treat patients with multiple TCRs sequentially in our Phase 1 study,” said Gavin MacBeath, CEO of TScan.

“Additionally, we submitted INDs for two additional TCRs in December and the 30-day review period with the FDA is ongoing. We look forward to dosing the first patient in the Phase 1 solid tumor clinical study in the first quarter and reporting clinical data, initially on patients treated with singleplexed therapy, and then on patients treated with multiplexed therapy, in 2024.”

 At the end of January, Bristol-Myers Squibb Company (NYSE: BMY) released encouraging findings from its CheckMate -8HW clinical study.

The study showcased data from its asset Opdivo (nivolumab) combined with Yervoy (ipilimumab) as a front-line treatment choice for microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC).

The combination therapy reduced the risk of disease progression or death by 79 percent versus chemotherapy in patients with these conditions.

“With research from the full CheckMate clinical development program, BMS has revolutionized the oncology landscape and helped change survival expectations for people with cancer,” said Dana Walker, vice president, global program lead, gastrointestinal and genitourinary cancers, Bristol Myers Squibb.

“These results build on the benefit of Opdivo and Yervoy in MSI-H/dMMR metastatic colorectal cancer as previously demonstrated in CheckMate -142 and reinforce our commitment to exploring the potential of these therapies to help more patients in need.”

 PDS Biotechnology Corporation is developing a treatment for many types of metastatic solid tumors, including colorectal and anal cancer, with its asset PDS-01ADC.

In November, PDS delivered a corporate update along with its Q3 2023 results, including interim safety and immune response data for its Phase 1/2 clinical trial evaluating docetaxel and PDS01ADC in metastatic prostate cancer patients.

Prostate-Specific Antigen (PSA) decline was seen in all 18 patients, and 61 percent of patients had at least a 60 percent decrease in PSA levels.

 “As the development of our IL12 fused antibody-drug conjugate or ADC, PDS01ADC, continues to progress, its potential to overcome key safety and efficacy limitations associated with existing cytokine therapy is reinforced,” said Frank Bedu-Addo, president and CEO of PDS Biotech.

“We are excited about the strides we are making across our pipeline, fueled by our commitment to developing groundbreaking therapies that revolutionize cancer treatments.”

 In 2024, C4 Therapeutics, Inc. anticipates new milestones for its asset CFT1946 in the first half of the year, including presenting preclinical data demonstrating differentiated activity in preclinical models of BRAF V600X melanoma, colorectal cancer, and more.

C4 also plans to present data from the ongoing Phase 1 dose-escalation trial in these cancers in the second half of 2024. Dosing of the first patient in CFT1946's Phase 1/2 clinical trial was announced at the beginning of 2023.

 “Dosing the first patient in the CFT1946 Phase 1/2 clinical trial marks the first degrader to enter clinical development to target BRAF-driven cancers,” said Adam Crystal, chief medical officer of C4 Therapeutics.

“Preclinically, in in vivo models, CFT1946 has demonstrated deeper and more durable activity than approved BRAF inhibitors, and promising activity in the setting of resistance to BRAF inhibitors. We look forward to advancing CFT1946 for patients with BRAF V600 mutant cancers, including non-small cell lung cancer, colorectal cancer, and melanoma.”